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Abstract
Background: Chronic Pseudomonas aeruginosa infection is a major cause of morbidity and mortality for individuals with cystic fibrosis (CF). P aeruginosa cross infection outbreaks have recently been reported at CF holiday camps and specialist centres. The mechanism of cross infection is unknown. A study was performed to look for the presence of epidemic strains of P aeruginosa in the environment of a CF centre during a cross infection outbreak and to examine their potential modes of spread between patients. Methods: Microbiological sampling of the environment of the CF facility was performed, including room air sampling. Individual P aeruginosa strains were identified by bacterial fingerprinting. The typing patterns were compared with those of epidemic strains responsible for cross infection among the patients. Results: Epidemic P aeruginosa strains were isolated from room air when patients performed spirometric tests, nebulisation, and airway clearance, but were not present in other areas of the inanimate environment of the CF centre. Conclusions: Aerosol dissemination may be the most important factor in patient-to-patient spread of epidemic strains of P aeruginosa during recent cross infection outbreaks at adult CF centres.
... While Manchester isolates have very rarely been isolated outside the United Kingdom, epidemiological links in these cases have always been present (96). The MA strain has been recovered from air samples but not from swabs of solid surfaces in the immediate vicinity of CF patients (215). The MA strain has not been observed in either non-CF populations or environmental surveys (174). ...
... Transmission through droplets or droplet nuclei has been suggested as the primary means of cross-infection of transmissible P. aeruginosa in CF by a number of investigators (187,215,(239)(240)(241)(242). When infectious agents are released into the air, they can remain suspended in the form of aerosols, droplets, or droplet nuclei and subsequently infect another individual (243). ...
... The investigators noted that at a ventilation rate of two hourly air changes, the removal of 90% of viable P. aeruginosa bacteria required approximately 50 min after the room had been cleared. Airborne transmission studies at CF centers have rarely cultured P. aeruginosa in the environment up to 3 h following clinical encounters by using spirometry, nebulized therapies, or airway clearance techniques (187,215). In a study by Ferroni et al. of 22 CF patients in single rooms on a hospital ward, more than 50% of cases had bedroom air samples that were culture positive for strains of P. aeruginosa that were genetically identical to those cultured in their respiratory tract. ...
Chronic lower airway infection with Pseudomonas aeruginosa is a major contributor to morbidity and mortality in individuals suffering from the genetic disease cystic fibrosis (CF). Whereas it was long presumed that each patient independently acquired unique strains of P. aeruginosa present in their living environment, multiple studies have since demonstrated that shared strains of P. aeruginosa exist among individuals with CF. Many of these shared strains, often referred to as clonal or epidemic strains, can be transmitted from one CF individual to another, potentially reaching epidemic status. Numerous epidemic P. aeruginosa strains have been described from different parts of the world and are often associated with an antibiotic-resistant phenotype. Importantly, infection with these strains often portends a worse prognosis than for infection with nonclonal strains, including an increased pulmonary exacerbation rate, exaggerated lung function decline, and progression to end-stage lung disease. This review describes the global epidemiology of clonal P. aeruginosa strains in CF and summarizes the current literature regarding the underlying biology and clinical impact of globally important CF clones. Mechanisms associated with patient-to-patient transmission are discussed, and best-evidence practices to prevent infections are highlighted. Preventing new infections with epidemic P. aeruginosa strains is of paramount importance in mitigating CF disease progression.
... Indeed, patients with CF infected with P. aeruginosa produce droplet nuclei containing viable bacteria.[17] Furthermore, studies using air sampling in CF clinical settings have demonstrated viable P. aeruginosa after physiotherapy and in corridors outside inpatient cubicle rooms housing patients with shared strain P. aeruginosa infection.[18, 19] Others have also suggested that airborne transmission is feasible, with shared and mucoid P. aeruginosa strains having a survival advantage.[20, ...
... Evidence of highly-prevalent shared P. aeruginosa strains within CF populations suggests person-to-person transmission.[10, 11, 26] Using air sampling equipment both in the clinical setting, viable P. aeruginosa have been demonstrated close to patients with shared strain P. aeruginosa infection.[18, 19] The clinical significance of these findings was unclear and led us to study the size distribution of cough aerosols and we have previously demonstrated P. aeruginosa can be present in aerosols generated by coughing.[17] ...
... Similarly, the model can help determine the time required to achieve a specified reduction in airborne P. aeruginosa in a CF clinic setting by taking into account the known room ventilation rate. Figure 3in the paper shows that it would take approximately 50-min to achieve this removal, due to combined effect of ventilation and biological inactivation, in a clinic room ventilated at the guideline rate of two ACH.[17][18][19]Figure 3also shows the time taken to remove specified amounts of P. aeruginosa at the ventilation guidelines prescribed for other clinical settings.[17] In addition to assuming that ventilation and biological decay are the major mechanisms which remove airborne P. aeruginosa from room air, we made two other key assumptions that underpin equation 1 and its use that affect the accuracy of our predictions. ...
... First, participants who cannot follow instructions such as infants, patients with dementia and confusional state, and those in critical condition are not qualified because spirometry requires effort and cooperation. Second, it may cause infection through microorganism transfer via mouthpiece 3,4 . Third, it cannot detect compartmental movement of the chest wall. ...
Spirometry is a standard method for assessing lung function. However, its use is challenging in some patients, and it has limitations such as risk of infection and inability to assess regional chest wall motion. A three-dimensional motion capture system using the one-pitch phase analysis (MCO) method can facilitate high precision measurement of moving objects in real-time in a non-contacting manner. In this study, the MCO method was applied to examine thoraco-abdominal (TA) wall motion for assessing pulmonary function. We recruited 48 male participants, and all underwent spirometry and chest wall motion measurement with the MCO method. A significant positive correlation was observed between the vital capacity (Spearman’s ρ = 0.68, p < 0.0001), forced vital capacity (Spearman’s ρ = 0.62, p < 0.0001), and tidal volume (Spearman’s ρ = 0.61, p < 0.0001) of spirometry and the counterpart parameters of MCO method. Moreover, the MCO method could detect regional rib cage and abdomen compartment contributions and could assess TA asynchrony, indicating almost complete synchronous movement (phase angle for each compartment: − 5.05° to 3.86°). These findings suggest that this technique could examine chest wall motion, and may be effective in analyzing chest wall volume changes and pulmonary function.
... Possible routes of transmission include fomite and aerosol spread, particularly from aerosol generating activities such as coughing during physiotherapy and forced expiration testing during visits to the pulmonary function laboratory. Airborne transmission of Mycobacterium tuberculosis through aerosolised droplets is well recognised [23], and cough aerosolisation of M. abscessus has also been described [6,[24][25][26]. Indirect contact transmission may have occurred via environmental contamination and fomite spread on contaminated equipment transferred between patients or via the hands of patients or health care workers. ...
Background:
Mycobacterium abscessus is an emerging pathogen in cystic fibrosis (CF) lung disease. Hospital transmission of M. abscessus has been described. This paper details the investigation into possible cross-transmission of M. abscessus locally at our paediatric hospital CF centre, and the subsequent infection control response.
Methods:
Whole genome sequencing (WGS) of M. abscessus respiratory isolates with epidemiological linkage analysis using hospital electronic medical records.
Results:
6.7% (22/328) of CF patients had M. abscessus isolated from respiratory specimens. WGS revealed a cluster of three patients with genomically related isolates that differed by <7 single nucleotide polymorphisms (SNPs), suggesting a shared recent ancestor and probable cross-transmission. Epidemiological investigation revealed multiple potential crossovers between patients with genomically similar M. abscessus isolates.
Conclusions:
Cross-infection of NTM occurs in CF hospital patients. Hospital infection control practices should be upgraded to reflect this. Consensus is needed between centres.
... P. аeruginosa также присутствует на коже 10-20 % здоровых носителей, которые могут быть источником хронической инфекции у больных МВ, вызванной данным микроорганизмом [12,14,21]. Однако не исключается и возможность заражения больного в результате контактов с растениями и плодами, которые могут быть колонизированы синегнойной палочкой. ...
The main causative agents of lung infection in patients with cystic fibrosis (CF) are P. aeruginosa, S. aureus and H. influenzae. In the last decade, gram-negative nonfermentative microorganisms (NFMO) - Вurkholderia cepacia complex (Bcc), Stenotrophomonas maltophilia, Achromobacter xylosoxidans and non-tuberculous mycobacteria, fungi of the genus Aspergillus have acquired the clinical significance. It is found that the chronic lung infection in 2/3 of the cases caused by association of microorganisms. Among hospitalized patients, in contrast to outpatients, these associations are represented by two, three or more species of microorganisms. The associations of P. aeruginosa + S. aureus (18,2 %) and P. aeruginosa + Bcc (9,1 %) are the most common. Other representatives - A. xylosoxidans, S. maltophilia and A. baumanii - is often identified in the associations of microorganisms. The focuses of chronic lung infections are formed in patients with increasing age. The dominant pathogens are P. aeruginosa and S. aureus. The methicillinresistant staphylococci and P. aeruginosa strains with a mucoid phenotype are of particular importance for cystic fibrosis patients. Bcc isolates from cystic fibrosis patients in Russia often belong to genomovar III A-B. cenocepacia. The Bcc strains colonize the lower airways of patients with CF and are able for long-term persistence and transmission from patient to patient. The resistance to many antibiotics is the main feature of the P. aeruginosa, S. aureus and Bcc strains. The strains of microorganisms with atypical phenotype (small colony variants) are formed under the action of the antibiotic. Infections caused by Bcc and other NFMO are difficult to identify and we need to use a wide range of bacteriological, biochemical, molecular biological techniques and mass spectrometry.
... Pseudomonas aeruginosa and other Pseudomonas species usually colonise moist surfaces [5], and have been implicated in airborne transmission of cystic fibrosis [6]. Few studies have documented their presence in indoor air of healthcare facilities [7,8,9] The study was undertaken to 1) characterise Gram-negative bacteria in indoor air of different hospitals; 2) characterise Pseudomonas sp. by phenotypic and genotypic methods; 3) determine the homology of study environmental isolates of Pseudomonas sp. and correlate with sequences of established pathogenic strains. ...
Background and objectives:
Pseudomonas species are nosocomial pathogens that are capable of colonising moist surfaces. Little is known whether they get airborne. The study was undertaken to 1) characterise Gram-negative bacteria in indoor air of different hospitals; 2) characterise Pseudomonas sp. by phenotypic and genotypic methods; 3) determine homology of study environmental Pseudomonas isolates and correlate with established pathogenic strains' sequences.
Methods:
Samples were collected (duplicates) at the time of peak activity, by exposing media-containing plates (blood agar and MacConkey agar) for 30 minutes. Plates were incubated aerobically at 37°C for 24-48 h. Microorganisms were identified by standard microbiological procedures. Polymerase chain reaction targeting Pseudomonas specific 16S-rDNA was performed to obtain 618 bp amplicons. Representative strains were sequenced and compared with established sequences of pathogenic Pseudomonas strains from existing database for evolutionary details.
Results:
A total of six hospitals comprising 13 wards, 7 intensive care units (ICUs) and 8 operating rooms (ORs) were sampled over one-year period. A variety of Gram-negative bacilli were isolated, of which Pseudomonas sp. was predominant. Indoor air of 10 wards (77%), 5 ICUs (71%), 4 ORs (50%) harboured Pseudomonas. Similar strains of Pseudomonas stutzeri were isolated from indoor air of different hospitals. Phylogenetic analysis showed these environmental strains to be closely related to the pathogenic Pseudomonas stutzeri strain from the GenBank database.
Conclusions:
Isolation of airborne Pseudomonas stutzeri from different hospitals suggests a possible new reservoir in the hospital environment, indicating the need for appropriate engineering control measures to contain the spread of these nosocomial agents.
... This organism is likely to have been transmitted during summer camps which were encouraged at that time to help increase the confidence and independence of young people with cystic fibrosis. These camps were attended by people with CF from the UK and Ireland and may have been the source for index cases in CF centres in the British Isles [26][27][28]. A number of important studies demonstrated the clonality of this organism and its ability to spread from patient to patient. ...
Bacterial infection is the primary initiator and driver of inflammation and lung injury in the airways of people with cystic fibrosis. Infection begins early in life and over time becomes chronic in many patients. Pseudomonas aeruginosa is the dominant pathogen in chronic infection and is associated with an accelerated decline in lung function, more frequent exacerbations, and reduced survival compared to people with no Gram-negative infection. Antibiotic eradication therapy is effective in delaying chronic infection with P. aeruginosa and can be employed repeatedly to new infections. When chronic infection develops, long-term inhaled antibiotics and azithromycin therapies reduce exacerbations, improve QoL, and may impact survival. Pulmonary exacerbations driven by infection and inflammation are associated with decline in lung function and reduced survival. Optimal therapy for these requires multiple antibiotics and close assessment of response. A number of other bacteria such as Staphylococcus aureus, Stenotrophomonas maltophilia, Achromobacter spp. and nontuberculous mycobacteria are an increasing problem in CF infection and bring new challenges to therapy.
Bio-aerosols are airborne particles that are living (bacteria, viruses and fungi) or originate from living organisms. Their presence in air is the result of dispersal from a site of colonization or growth. The health effects of bio-aerosols including infectious diseases, acute toxic effects, allergies and cancer coupled with the threat of bioterrorism and SARS have led to increased awareness on the importance of bio-aerosols. The evaluation of bio-aerosols includes use of variety of methods for sampling depending on the concentration of microorganisms expected. There have been problems in developing standard sampling methods, in proving a causal relationship and in establishing threshold limit values for exposures due to the complexity of composition of bio-aerosols, variations in human response to their exposure and difficulties in recovering microorganisms. Currently bio-aerosol monitoring in hospitals is carried out for epidemiological investigation of nosocomial infectious diseases, research into airborne microorganism spread and control, monitoring biohazardous procedures and use as a quality control measure. In India there is little awareness regarding the quality of indoor air, mould contamination in indoor environments, potential source for transmission of nosocomial infections in health care facilities. There is an urgent need to undertake study of indoor air, to generate baseline data and explore the link to nosocomial infections. This article is a review on composition, sources, modes of transmission, health effects and sampling methods used for evaluation of bio-aerosols, and also suggests control measures to reduce the loads of bio-aerosols.
Bronchiectasis is a chronic lung disease (CLD) characterized by irreversible bronchial dilatation noted on computed tomography associated with chronic cough, ongoing viscid sputum production, and recurrent pulmonary infections. Patients with bronchiectasis can be classified into two groups: those with cystic fibrosis and those without cystic fibrosis. Individuals with either cystic fibrosis related bronchiectasis (CFRB) or noncystic fibrosis related bronchiectasis (NCFRB) experience continuous airway inflammation and suffer airway architectural changes that foster the acquisition of a unique polymicrobial community. The presence of microorganisms increases airway inflammation, triggers pulmonary exacerbations (PEx), reduces quality of life (QOL), and, in some cases, is an independent risk factor for increased mortality. As there is no cure for either condition, prevention and control of infection is paramount. Such an undertaking incorporates patient/family and healthcare team education, immunoprophylaxis, microorganism source control, antimicrobial chemoprophylaxis, organism eradication, daily pulmonary disease management, and, in some cases, thoracic surgery. This review is a summary of recommendations aimed to thwart patient acquisition of pathologic organisms, and those therapies known to mitigate the effects of chronic airway infection. A thorough discussion of airway clearance techniques and treatment of or screening for nontuberculous mycobacteria (NTM) is beyond the scope of this discussion.
Background:
Chronic infection with Pseudomonas aeruginosa (PA) in cystic fibrosis (CF) is a source of much morbidity and mortality. Eradication of early PA infection is possible, but can recur in many individuals. We sought to examine strategies to delay the time to PA recurrence in people with CF.
Objectives:
To establish whether secondary prevention strategies, using antibiotics or other therapies, increase the chances of people with CF remaining free from PA infection following successful eradication therapy.
Search methods:
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 21 August 2019.
Selection criteria:
Randomised controlled trials (and quasi-randomised trials where the risk of bias was low) comparing any treatment modality aimed at preventing recurrence of PA infection with placebo, standard therapy or any other treatment modality in people with CF who have undergone successful eradication of PA.
Data collection and analysis:
Two review authors independently assessed trials for inclusion and risk of bias. Quality of the evidence was assessed using GRADE. Conflicts were resolved by discussion and the opinion of a third review author was sought where necessary. Only a subset of participants in the included trial were eligible, therefore individual participant data were requested and obtained from the trial investigators.
Main results:
We included one trial (n = 306) in the review; however, only 253 participants had undergone successful eradication of PA, so fulfilling the inclusion criteria for our review. Information presented relates only to the included subset of participants. The trial recruited children aged one to 12 years (mean (standard deviation (SD)) age of 5.8 (3.5) years), 129 participants (51.0%) were female and the median follow-up was 494 days. We compared cycled therapy with tobramycin inhalation solution (TIS), in which participants underwent 28 days of TIS every three months, with culture-based therapy, in which participants were only prescribed medication when a quarterly sputum sample was positive for PA. Reasons for downgrading the quality of the evidence included applicability (only included children), incomplete outcome data and a small number of participants. The time to next isolation of PA was probably shorter with cycled TIS therapy than with culture-based therapy, hazard ratio (HR) 2.04 days (95% confidence interval (CI) 1.28 to 3.26) (moderate-quality evidence). This is in contrast to the main publication of the only included trial, which examined rate of PA positivity rather than time to PA infection and included participants not eligible for inclusion in this review. At the end of the trial, there was no difference between the cycled and culture-based groups in the change from baseline in forced expiratory volume in one second (FEV1) L, mean difference (MD) 0.0 L (95% CI -0.09 to 0.09) or in FEV1 % predicted, MD 0.70% (95% CI -4.33 to 5.73) (both very low-quality evidence). There was no difference in the change from baseline for FVC between the groups. There was also no difference in the frequency of pulmonary exacerbations between groups, MD -0.18 (95% CI -0.51 to 0.14) (moderate-quality evidence). Similarly, there was no difference between groups in the risk of participants developing novel resistant bacteria, RR 1.00 (95% CI 0.67 to 1.5) (moderate-quality evidence). There were more severe adverse events in the cycled group, but the type of treatment probably makes little or no difference to the results, RR 0.65 (95% CI 0.39 to 1.11) (moderate-quality evidence). There was no difference between groups in the change in weight or height from baseline or in rates of adherence to tobramycin or all trial medicines. The included trial did not assess changes in quality of life, the time to chronic infection with PA or the cost-effectiveness of treatment.
Authors' conclusions:
Cycled TIS therapy may be beneficial in prolonging the time to recurrence of PA after successful eradication, but further trials are required, specifically addressing this question and in both adults and children.
Introduction: Cystic fibrosis is a life-limiting genetic condition characterized by recurrent pulmonary infection. Acquisition of infection can occur from environmental reservoirs, person-to-person transmission and from the healthcare environment. Primary prevention of infections through infection prevention and control measures is an important strategy in cystic fibrosis care.
Areas covered: Here we present a systematic review of the evidence base around infection prevention and control in cystic fibrosis. We found 36 studies and 7 guidelines that met our inclusion criteria. Strategies covered include cohort segregation, individual segregation, hand hygiene, facemasks, combination strategies, equipment strategies and adherence. Quality of evidence overall was deemed low or very low. Most guideline recommendations have little or no evidence to support them.
Expert opinion: Although low quality, there is an abundance of evidence suggesting segregation is beneficial in reducing pathogen spread. Undertaking high quality studies may therefore be ethically challenging. Large-scale registry studies may provide a better strategy for answering questions on efficacy of infection control policy. With the rise of antibiotic resistance, effective eradication of cystic fibrosis pathogens is becoming more difficult so primary prevention through infection control will become increasingly important over the coming years.
Multistrain diseases, which are infected through individual contacts, pose severe public health threat nowadays. In this paper, we build competitive and mutative two‐strain edge‐based compartmental models using probability generation function (PGF) and pair approximation (PA). Both of them are ordinary differential equations. Their basic reproduction numbers and final size formulas are explicitly derived. We show that the formula gives a unique positive final epidemic size when the reproduction number is larger than unity. We further consider competitive and mutative multistrain diseases spreading models and compute their basic reproduction numbers. We perform numerical simulations that show some dynamical properties of the competitive and mutative two‐strain models.
In Australia and New Zealand, >50% of people with cystic fibrosis (CF) are adults and many of these people are pursuing vocational training and undertaking paid employment. More than 6% of adults with CF are working in health care. There is limited guidance in literature to support health care workers with CF (HCWcf) in training and in employment to support safe practice and to provide protection for themselves and their patients from the acquisition of health care associated infection. A multidisciplinary team of CF and Infectious Disease Clinicians, Infection Prevention and Control Practitioners, HCWcf, academic experts in medical ethics and representatives from universities, appraised the available evidence on the risk posed to and by HCWcf. Specific recommendations were made for HCWcf, CF health care teams, hospitals and universities to support the safe practice and appropriate support for HCWcf.
Cockroaches, the important indoor sanitary pests in urban worldwide. In China, there are six species of dominant indoor cockroaches which are increasingly hard to control due to their high adaptability, strong fecundity and extensive insecticide resistance. These cockroaches harbour abundant microorganisms varying from bacteria to viruses, fungi and protists, which have formed an interdependent symbiotic relationship with hosts in the process of long-term coevolution. A growing research has revealed that symbionts can modulate limited metabolic networks, thereby expanding ecological niches of host insects as a significant regulatory factor in insect growth and development. Therefore, in-depth study on the mechanisms of symbiont–insect interactions can shed light on a new perspective for pest prevention and control technology. Here, we give a general overview on classification and hazards of indoor cockroaches in China, as well as species, distribution and transmission mechanism of symbionts within cockroaches. Besides, we mainly discuss the interactions between insects and symbionts from the following aspects: nutritional physiology, reproductive regulation, pesticide resistance, defence, behaviour and so on. Based on the earlier symbiotic interactions, we propose some promising new insights into integrated pest management of cockroaches (i.e., utilizing symbionts to control cockroaches), such as application of Wolbachia to restrict population number, utilization of interactions between symbionts and entomopathogenic fungi including synergism or antagonism to accelerate host death, limiting host's vectorial capacity via paratransgenesis, push–pull strategy.
The airborne route is a potential pathway in the person-to-person transmission of bacterial strains among cystic fibrosis (CF) populations. In this cross-sectional study, we investigate the physical properties and survival of common non-Pseudomonas aeruginosa CF pathogens generated during coughing. We conclude that Gram-negative bacteria and Staphylococcus aureus are aerosolised during coughing, can travel up to 4 m and remain viable within droplet nuclei for up to 45 min. These results suggest that airborne person-to-person transmission is plausible for the CF pathogens we measured.
Résumé
Introduction
Le test de marche de six minutes (TM6) est fréquemment utilisé en pneumologie. Certains patients à risque d’infection croisée doivent porter un masque de soins pour se protéger et ce parfois pendant l’effort.
But de l’étude
Évaluer l’effet du port d’un masque de soins sur la distance parcourue lors du TM6 chez des sujets sains.
Matériel et méthode
Étude prospective portant sur 44 sujets sains. Après un TM6 de familiarisation, ils ont réalisé aléatoirement un TM6 avec et sans port d’un masque de soins. La distance et l’évolution de la dyspnée, de la fréquence cardiaque et de la saturation en oxygène ont été mesurées.
Résultats
La distance n’est pas influencée par le port du masque de soins (p = 0,99). L’augmentation de la dyspnée est significativement plus élevée lors du port du masque de soins (+5,6 vs +4,6 ; p < 0,001) et la différence est cliniquement significative. Par contre, il n’y a pas d’influence sur les autres paramètres.
Conclusion
Le port du masque de soins ne modifie pas la distance parcourue lors du TM6 mais augmente significativement et cliniquement la dyspnée.
Background
Frequently encountered multidrug-resistant bacterial isolates of P. aeruginosa and A. baumannii are common and prevalent in a hospital environment. The aim of this study was to determine the prevalence and pattern of antibiotic resistance, extended spectrum and metallo beta-lactamase producing P. aeruginosa and A. baumannii isolates from restricted settings of indoor air hospital environment.
Methods
A hospital-based cross-sectional study was conducted in Wolaita Sodo University Teaching and referral Hospital, Ethiopia from December 1/2015 to April 30/2015. The Air samples were collected from delivery room, intensive care unit and operation theatre of the hospital by active, Anderson six slate sampler technique during the first week of the months, twice a week during Monday’s and Friday’s. Standard microbiological procedures were followed to isolate P. aeruginosa and A. baumannii. Susceptibility testing was performed on isolates using the Kirby-Bauer disk diffusion technique. Extended spectrum beta lactamase production was detected by double disc synergy test and Imipenem-resistant isolates were screened for producing Metallo-beta lactamase.
Results
A total number of 216 indoor air samples were collected from the delivery room, intensive care unit, and operation room. Correspondingly, 43 A. baumannii isolates were identified (13 from delivery room, 21 from intensive care unit and 9 from operation room). Likewise 24 P. aeruginosa isolates were obtained (4 from delivery room, 13 from intensive care unit and 7 from operation room). Extended spectrum beta lactamase and metalo-beta lactamase production were observed in 24 (55.8%) and 13 (30.2%) isolates of A. baumannii respectively, whereas P. aeruginosa showed 15 (62.5%) extended spectrum beta lactamase and 9 (37.5%) metallo-beta lactamase production.
Conclusions
Extended spectrum beta lactamase and metallo-beta lactamase producing bacteria in hospital air is a new dimension for specific setting of the study area where antimicrobial resistance is increasing and surgical site infection is prevalent. So, identification of these microorganisms has a great role in reducing the burden of antibiotic resistance and could also provide a significant input for framing hospital infection control policies.
Rationale:
People with cystic fibrosis (CF) generate Pseudomonas aeruginosa in droplet nuclei during coughing. The use of surgical masks has been recommended in healthcare settings to minimise pathogen transmission between CF patients.
Objective:
To determine if face masks and cough etiquette reduce viable P. aeruginosa aerosolised during cough.
Methods:
Twenty-five adults with CF and chronic P. aeruginosa infection were recruited. Participants performed six talking and coughing maneuvers, with or without face masks (surgical and N95) and hand covering the mouth when coughing (cough etiquette) in an aerosol-sampling device. An Andersen Impactor sampled the aerosol at 2-meters from each participant. Quantitative sputum and aerosol bacterial cultures were performed and participants rated the mask comfort levels during the cough maneuvers.
Measurements and main results:
During uncovered coughing (reference maneuver), 19/25 (76%) participants produced aerosols containing P. aeruginosa, with a positive correlation found between sputum P. aeruginosa concentration (CFU/mL) and aerosol P. aeruginosa CFUs. There was a reduction in aerosol P. aeruginosa load during coughing with surgical mask, coughing with N95 mask and cough etiquette compared with uncovered coughing (p<0.001). A similar reduction in total CFUs was observed for both masks during coughing, yet participants rated surgical masks more comfortable (p=0.013). Cough etiquette provided approximately half the reduction of viable aerosols of the mask interventions during voluntary cough. Talking was a low viable aerosol producing activity.
Conclusions:
Face masks reduce cough generated P. aeruginosa aerosols, with the surgical mask providing enhanced comfort. Cough etiquette was less effective at reducing viable aerosols.
The molecular epidemiology of Pseudomonas aeruginosa cross-colonization isolates has received limited attention in the non-outbreak setting. Also the roles of P. aeruginosa resistance and virulence in cross-colonization need to be further studied. This study aims to launch a tracking investigation to determine the epidemiological relationship of P. aeruginosa clinical and environmental isolates, identify the cross-colonization routes, and characterize the resistance and virulence properties of clonal clusters and sporadic strains in the respiratory care wards of a tertiary care hospital. A total of 436 patients were screened for P. aeruginosa on admission and after admission, and samples taken from their immediate ward environment, including faucet, doorknob, bedrail, pillow, quilt and mattress. All P. aeruginosa isolates were analyzed with Pulsed-Field Gel Electrophoresis (PFGE). Fingerprint analysis determined similarity and relatedness between isolates. PFGE for 100 P. aeruginosa isolates were obtained from 74 inpatients and 26 environment mediums. Phylogenetic analysis revealed 20 distinct clusters, representing the diversity of isolates in the non-outbreak setting. According to identical genotypes, there was clear process of cross-colonization from the ward environment to inpatients, indicating faucet, bedrail and pillow as the main propagation mediums that had been contaminated by P. aeruginosa clonal isolates previously detected in patients. In the remaining clusters there was an indirect link to the patient-to-patient transmission in the absence of positive samples from the ward environment and the aerosol. As compared to sporadic strains of P. aeruginosa, clonal clusters are more capable of producing high-level biofilm, developing multi-drug resistance and inducing high-degree cytotoxicity. We insist that constant cross-colonization of P. aeruginosa clonal isolates will pose a long-term serious threat to nosocomial outbreaks. Determining contaminated mediums in the non-outbreak setting and understanding the resistance and virulence properties contribute to targeted control measures to protect inpatients at risk of P. aeruginosa infection.
Pseudomonas aeruginosa (Pa) is one of the major bacterial pathogens causing nosocomial infections. During the past few decades, multidrug-resistant (MDR) and extensively drug-resistant (XDR) lineages of Pa have emerged in hospital settings with increasing numbers. However, it remains unclear which determinants of Pa facilitated this spread. A total of 211 clinical XDR and 38 susceptible clinical Pa isolates (nonXDR), as well as 47 environmental isolates (EI), were collected at the Heidelberg University Hospital. We used RAPD PCR to identify genetic clusters. Carriage of carbapenamases (CPM) and virulence genes were analyzed by PCR, biofilm formation capacity was assessed, in vitro fitness was evaluated using competitive growth assays, and interaction with the host’s immune system was analyzed using serum killing and neutrophil killing assays. XDR isolates showed significantly elevated biofilm formation (p < 0.05) and higher competitive fitness compared to nonXDR and EI isolates. Thirty percent (62/205) of the XDR isolates carried a CPM. Similarities in distribution of virulence factors, as well as biofilm formation properties, between CPM+ Pa isolates and EI and between CPM- and nonXDR isolates were detected. Molecular typing revealed two distinct genetic clusters within the XDR population, which were characterized by even higher biofilm formation. In contrast, XDR isolates were more susceptible to the immune response than nonXDR isolates. Our study provides evidence that the ability to form biofilms is an outstanding determinant for persistence and endemic spread of Pa in the hospital setting.
Rationale
Epidemic Pseudomonas aeruginosa (PA) plays an important role in cystic fibrosis (CF) lung disease. A novel strain, the ‘Prairie Epidemic Strain’ (PES), has been identified in up to 30% of patients in Prairie-based Canadian CF centres.
Objective
To determine the incidence, prevalence and long-term clinical impact of PES infection.
Methods
A cohort of adults with CF was followed from 1980 to 2014 where bacteria isolated from clinical encounters were prospectively collected. Strain typing was performed using pulse-field gel electrophoresis and multilocus sequence typing. Patients were divided into one of four cohorts: no PA, transient PA, chronic PA with unique strains and chronic PES. Proportional Cox hazard and linear mixed models were used to assess for CF-associated respiratory death or transplantation, and rates of %FEV1 and body mass index (BMI) decline.
Results
274 patients (51.7% male) were analysed: 44––no PA, 29––transient PA, 137––unique PA, 64––PES. A total of 92 patients (33.6%) died or underwent lung transplantation (2423.0 patient-years). PES infection was associated with greater risk of respiratory death or lung transplant compared with the no PA group (aHR, 3.94 (95% CI 1.18 to 13.1); p=0.03) and unique PA group (aHR, 1.75 (95% CI 1.05 to 2.92) p=0.03). Rate of lung function decline (%FEV1 predicted) was greatest in the PES group (1.73%/year (95% CI 1.63% to 1.82%); p<0.001). BMI improved over time but at an attenuated rate in the PES group (p=0.001).
Conclusions
Infection with PES was associated with increased patient morbidity through three decades and manifested in an increased risk of respiratory death and/or lung transplantation.
This is the protocol for a review and there is no abstract. The objectives are as follows: To establish whether secondary prevention strategies, using antibiotics or other therapies, increase the chances of PWCF remaining free from PA infection following successful eradication therapy.
Particulate respirators designed to filtrate fine particulate matters usually do not possess antimicrobial functions. The current study aimed to functionalize particulate respirators with silver nanoparticles (nanosilver or AgNPs), which have excellent antimicrobial activities, utilizing a straightforward and effective method. We first enhanced the nanosilver-coating ability of nonwoven fabrics from a particulate respirator through surface modification by sodium oleate. The surfactant treatment significantly improved the fabrics' water wet preference where the static water contact angles reduced from 122° to 56°. Both macroscopic agar-plate tests and microscopic scanning electron microscope (SEM) characterization revealed that nanosilver functionalized fabrics could effectively inhibit the growth of two model bacterial strains (i.e., Staphylococcus aureus and Pseudomonas aeruginosa). The coating of silver nanoparticles would not affect the main function of particulate respirators (i.e., filtration of fine air-borne particles). Nanosilver coated particulate respirators with excellent antimicrobial activities can provide real-time protection to people in regions with severe air pollution against air-borne pathogens.
Pseudomonas aeruginosa is a remarkably versatile environmental bacterium with an extraordinary capacity to infect the cystic fibrosis (CF) lung. Infection with P. aeruginosa occurs early, and although eradication can be achieved following early detection, chronic infection occurs in over 60% of adults with CF. Chronic infection is associated with accelerated disease progression and increased mortality. Extensive research has revealed complex mechanisms by which P. aeruginosa adapts to and persists within the CF airway. Yet knowledge gaps remain, and prevention and treatment strategies are limited by the lack of sensitive detection methods and by a narrow armoury of antibiotics. Further developments in this field are urgently needed in order to improve morbidity and mortality in people with CF. Here, we summarize current knowledge of pathophysiological mechanisms underlying P. aeruginosa infection in CF. Established treatments are discussed, and an overview is offered of novel detection methods and therapeutic strategies in development.
In many countries numbers of adults with cystic fibrosis (CF) exceed that of children, with median survival predicted to surpass 50 years. Increasing longevity is, in part, due to intensive therapies including eradication of early infection and suppressive therapies and pulmonary exacerbations. Initial infections with common CF pathogens are thought to arise from the natural environment. We review the impact of climate and environment on infection in CF Specifically, several studies indicate that higher ambient temperatures, proximity to the equator and the summer season may be linked to the increased prevalence of P. aeruginosa in people with CF. The environment may also play an important role in the acquisition of Gram negative organisms other than P. aeruginosa. There is emerging data suggesting that climatic and environmental factors are likely to impact on the risk of infection with NTM and fungi in people which are found extensively throughout the natural environment.
In cystic fibrosis (CF), Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutations were associated with increased antibiotic resistance and worse clinical outcomes. Two-hundred-and-one P. aeruginosa isolates (163 represented a dominant Australian shared strain, AUST-02) from two Queensland CF centres over two distinct time-periods (2001-2002 and 2007-2009) underwent mexZ and lasR sequencing. Broth microdilution antibiotic susceptibility testing in a subset of isolates was also performed. We identified a novel AUST-02 subtype (M3L7) in adults attending a single Queensland CF centre. This M3L7 subtype was multi-drug resistant and had significantly higher antibiotic minimum inhibitory concentrations than other AUST-02 subtypes. Prospective molecular surveillance using polymerase chain reaction assays determined the prevalence of the 'M3L7' subtype at this centre during 2007-2009 (170 patients) and 2011 (173 patients). Three-year clinical outcomes of patients harbouring different strains and subtypes were compared. MexZ and LasR sequences from AUST-02 isolates were more likely in 2007-2009 than 2001-2002 to exhibit mutations (mexZ: odds ratio (OR) = 3.8; 95% confidence interval (CI): 1.1-13.5 and LasR: OR = 2.5; 95%CI: 1.3-5.0). Surveillance at the adult centre in 2007-2009 identified M3L7 in 28/509 (5.5%) P. aeruginosa isolates from 13/170 (7.6%) patients. A repeat survey in 2011 identified M3L7 in 21/519 (4.0%) P. aeruginosa isolates from 11/173 (6.4%) patients. The M3L7 subtype was associated with greater intravenous antibiotic and hospitalisation requirements, and a higher 3-year risk of death/lung transplantation, than other AUST-02 subtypes (adjusted hazard ratio [HR] = 9.4; 95%CI: 2.2-39.2) and non-AUST-02 strains (adjusted HR = 4.8; 95%CI: 1.4-16.2). This suggests ongoing microevolution of the shared CF strain, AUST-02, was associated with an emerging multi-drug resistant subtype and possibly poorer clinical outcomes.
Person-to-person transmission is a potential pathway of Pseudomonas aeruginosa acquisition in cystic fibrosis. Reports of cross-infection of shared cystic-fibrosis-specific P aeruginosa strains across large geographical distances are concerning. Therefore, we aimed to assess the extent to which patient movement between cystic fibrosis centres contributes to dissemination.
We did a cross-sectional study to assess movement of patients with cystic fibrosis who were infected with P aeruginosa between Sept 3, 2007, and June 16, 2010, at 18 Australian cystic fibrosis centres. We applied social network analysis to patient movement data from P aeruginosa-infected patients to assess the role of patient mobility in P aeruginosa genotype prevalence. We generated networks linking treatment centres based on the movement of patients attending adult and paediatric cystic fibrosis centres, and compared these with the movement of patients infected with all P aeruginosa strains, unique strains, and predominant Australian shared strains (AUST-01 and AUST-02). We summarised connectivity using degree centrality, in-degree centrality, out-degree centrality, and k-core estimates. Infection control and surveillance practices were also assessed by use of a questionnaire.
983 patients (mean age 25 years [SD 10]; 551 [56%] male) provided 2887 P aeruginosa isolates for ERIC-PCR genotyping, which yielded 531 distinct genotypes: 493 unique strains in 373 patients and 38 shared strains in 610 patients. AUST-01 infections were associated with higher in-degree centrality (p=0·004) and k-core (p=0·005) estimates and AUST-02 infections with higher degree centrality (p=0·002), out-degree centrality (p=0·002), and k-core (p=0·007) estimates for the previous health-care facilities; associations for the present cystic fibrosis centre were not significant. These findings were significant for adult patients (AUST-01 in-degree centrality p=0·004 and k-core p=0·005; AUST-02 degree centrality p=0·004, out-degree centrality p=0·003, and k-core p=0·007), but not for paediatric patients. By contrast, infections with unique strains were associated with a lower k-core estimate for the present cystic fibrosis centre overall (p<0·0001); this finding was significant in adults (p<0·0001), but not in paediatric patients.
Our results show that the connectivity of cystic fibrosis centres, as measured by the movement of patients, seems to be an important risk factor for the acquisition of shared P aeruginosa strain infections. These results show the importance of prioritising infection control interventions (eg, prospective molecular surveillance for shared P aeruginosa strains, strict universal infection control precautions, and hospital design and ventilation) to limit P aeruginosa cross-infection between patients with cystic fibrosis.
Australian National Health and Medical Research Council; Children's Health Foundation Queensland; Office of Health and Medical Research, Queensland Health; European Respiratory Society-European Union; Australian Cystic Fibrosis Research Trust; Prince Charles Hospital Foundation; and Rotary Australia.
Copyright © 2015 Elsevier Ltd. All rights reserved.
The acquisition of Pseudomonas aeruginosa in cystic fibrosis (CF) is associated with lower survival, decreased lung function, worse radiological scores, increased exacerbations and reduced nutritional status. Open water is a known reservoir and a potential source of exposure to P. aeruginosa.
Twenty eight adult CF patients who had no history of P. aeruginosa and had negative P. aeruginosa IgG antibody levels, were matched by age and sex with 28 CF patients with chronic P. aeruginosa colonization. Straight line and closest walking distance from patient's residence to the nearest "blue space", i.e. surface water as determined by Google Earth, were compared between the two groups, and odds ratios (OR) were estimated using conditional logistic regression.
Patients who were never infected with P. aeruginosa lived significantly further away from a natural water source than P. aeruginosa colonized patients, both when considering shortest walking distance (mean 487m vs 308m, p=0.014) and beeline (mean 324m vs 202m, p=0.021). Conditional logistic regression (correcting for FEV1%) revealed ORs for chronic P. aeruginosa colonization of 0.35 (95% CI 0.13-0.98; p=0.045) and 0.12 (95% CI 0.02-0.81; p=0.028) for each doubling in the beeline or walking distance, respectively, between residence and open water.
We discovered that adult CF patients without P. aeruginosa infection live significantly further from blue space than CF patients with chronic P. aeruginosa colonization. Within the limitations of a case-control study, this may indicate that natural open water represents a source of infection by P. aeruginosa in CF.
The study was approved by the local ethical committee of the UZ Leuven, Belgium (ML-5028).
Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
The spectrum of bacterial pathogens encountered in cystic fibrosis (CF) lung disease has expanded over the last decade. In addition to established pathogens, such as Pseudomonas aeruginosa, Burkholderia cepacia complex and Staphylococcus aureus, novel Gram-negative non-fermenter bacteria and non-tuberculous mycobacteria have gained in clinical significance. Air sampling performed in inpatient and outpatient clinics, and analysis of cough aerosols expelled by CF patients provides evidence for potential airborne transmission of CF pathogens. Two outbreaks of 'Mycobacterium abscessus subsp. massiliense' have been reported among CF patients, raising the question of airborne transmission of non-tuberculous mycobacteria. In response to newer epidemiological evidence, international infection control guidance documents have changed. Guideline documents agree on the importance of specifications for ventilation when planning new CF inpatient facilities. New CF units should consider providing negative-pressure inpatient and outpatient rooms to diminish the risk of airborne contamination of ward corridors and communal areas. Air exchange rates of inpatient rooms and pulmonary function testing rooms need to be considered and optimized whenever possible. International guidelines disagree as to whether patients should be requested to wear masks in the hospital environment.
Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
The aim of this study was to evaluate the concentration and size distribution of airborne culturable Staphylococcus aureus (S. aureus) (including MRSA) in Chinese public buildings. Air samples were collected, using six-stage Andersen sampler from five different public buildings in one large Chinese community. The mean indoor concentrations of the total and respirable airborne S. aureus were 72 and 50 CFU/m3 in the general hospital, 72 and 49 CFU/m3 in the kindergarten, 76 and 52 CFU/m3 in the hotel, 84 and 57 CFU/m3 in the movie theater, and 55 and 40 CFU/m3 in the university classroom. Respirable S. aureus amounted to approximately 57–73 % of the total S. aureus concentrations. Mean total and respirable concentrations of airborne MRSA were 32 and 20 CFU/m3 in the general hospital, 20 and 13 CFU/m3 in the kindergarten, 23 and 16 CFU/m3 in the hotel, 33 and 20 CFU/m3 in the movie theater, and 24 and 17 CFU/m3 in the university classroom. Respirable MRSA amounted to approximately 61–72 % of the total MRSA concentrations. The ratios of indoor and outdoor concentration for airborne S. aureus and MRSA were more than 1.0 in all the investigated public buildings. The size distribution results showed relatively high collection rates on stage 4 (2.1–3.3 μm) for both airborne culturable S. aureus and MRSA regardless of the type of public buildings.
For patients with cystic fibrosis (CF) Pseudomonas aeruginosa infection is a major contributor to progressive lung disease. While colonizing strains are thought to be primarily environmental, which environments are important in lung colonization is unclear.
We took 11,674 samples from a broad range of sites over 3-8 visits to homes with (7) and without (8) CF patients.
Twenty-eight percent of sampled drains yielded P. aeruginosa at least once, and a general mixed linear model estimated that 6.3% of samples from drains yield P. aeruginosa. This is more than eight times the estimated recovery from any other type of household environment.
These findings implicate drains as important potential sources of P. aeruginosa infection. They suggest that maximizing P. aeruginosa control efforts for drains would reduce exposure with minimal extra burden to CF patients and families.
Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:
1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF . These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.
2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF . These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.
Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission.
Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured.
Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73-0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room.
Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.
Hemorrhagic pneumonia is an acute and fatal disease of farmed mink caused by Pseudomonas aeruginosa. The pathogenesis of this disease has not yet been resolved. Mink are the only animals known to be susceptible to acute, contagious, and fatal lung infections caused by P. aeruginosa. The purpose of this study was to investigate the correlation between dose-response and season of infection and to clarify whether Danish mink are carriers of P. aeruginosa on their nasal mucosa during the season for hemorrhagic pneumonia. To elucidate the pathogenesis of the disease, an infectious dose-response trial was carried out on adult mink and mink kits, both in the season for hemorrhagic pneumonia (November) as well as out of season (July). It proved difficult to infect mink via the intra-nasal route. Only 4 out of 60 infected mink developed clinical disease and were euthanized, all of them in November, illustrating that predisposing factors in the mink itself and not infectious dose might be crucial for disease development. We were able to culture P. aeruginosa from the nasal cavity of the clinically healthy experimental mink 8 d after inoculation. This indicated that the mink can carry P. aeruginosa on their nasal mucosa without developing the disease. It was not possible, however, to culture P. aeruginosa from the nasal cavity of clinically healthy mink obtained from farms in November, which indicates that the organism is not a normal part of the nasal mucosal flora of mink.
Les infections respiratoires jouent un rôle délétère majeur dans l’évolution des mucoviscidoses. Des infections croisées et des épidémies ont été documentées chez ces patients, justifiant une prévention rigoureuse.
'Covering your cough' reduces droplet number, but its effect on airborne pathogen transmission is less clear. The World Health Organization specifically recommends cough etiquette to prevent the spread of Mycobacterium tuberculosis, but implementation is generally poor and evidence supporting its value is lacking.
We constructed a model to assess 'real life' transmission risk by counting viable pathogens from aerosols produced by coughing patients, thus allowing the assessment of outward protection measures in a standardised fashion. During the validation process, we focused on rod-shaped bacteria as surrogates for M. tuberculosis.
The Cough Cylinder enabled us to sample Pseudomonas aeruginosa, Escherichia coli and mycobacteria from aerosols produced by patients with cystic fibrosis, primary ciliary dyskinesia and tuberculosis. Pathogens in droplets and in airborne particles could be sampled. Delayed air sampling allowed specific measurement of persistent airborne particles.
This novel experimental system allows measurement of aerosol pathogen spread in a highly standardised fashion. It also offers the possibility to assess the impact of different interventions to limit aerosol transmission.
Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia there is only limited evidence of unrelated patients sharing indistinguishable P. aeruginosa strains. We therefore examined the point-prevalence, distribution, diversity and clinical impact of P. aeruginosa strains in Australian CF patients nationally.Nine-hundred and eighty-three patients attending 18 Australian CF centres provided 2,887 sputum P. aeruginosa isolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant.Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres respectively. AUST-01 was associated with significantly greater treatment requirements than unique P. aeruginosa strains.Multiple clusters of shared P. aeruginosa strains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings.
Epidemic Pseudomonas aeruginosa have been identified in cystic fibrosis (CF) patients worldwide. The Australian Epidemic Strain-2 (AES-2) infects up to 40% of patients in three eastern Australian CF clinics. To investigate whether AES-2 isolates from chronically infected CF adults differentially express well-conserved genes potentially associated with transmissibility, we compared the transcriptomes of planktonic and biofilm-grown AES-2, infrequent P. aeruginosa clones and the reference P. aeruginosa PAO1 using the Affymetrix PAO1 array. The most interesting findings emerged from comparisons of planktonic and biofilm AES-2. AES-2 biofilms upregulated Type III secretion system genes, but downregulated quorum-sensing (QS)-regulatory genes, except lasR, QS-regulated, oxidative-stress and iron-storage genes. QS-regulated and iron-storage genes were downregulated to a greater extent in AES-2 biofilms compared with infrequent clone and PAO1 biofilms, suggesting enhanced anaerobic respiration in AES-2. Chitinase and chitin-binding protein maintained high expression in AES-2 biofilms compared with infrequent clone and PAO1 biofilms. Planktonic AES-2 upregulated QS regulators and QS-regulated genes, iron acquisition and aerobic respiration genes, and had high expression of Group III Type IV pilA compared with low expression of Group I Type IV pilA in infrequent clones. Together, these properties may enhance long-term survival of AES-2 in CF lung and contribute to its transmissibility.
Background:
Colonized or infected patients pose a significant risk to noncolonized patients occupying the same room. The aim of this study was to investigate how far Enterococcus spp can spread from isolated and nonisolated patients.
Methods:
Conventional microbiological methods were used to recover enterococci from the air and from 62 high-contact sites located within the near-patient and wider ward environment. Samples were collected twice weekly for 17 weeks. The similarity between isolates was determined via pulsed-field gel electrophoresis.
Results:
Vancomycin-susceptible enterococci (VSE) were recovered from 352 of 2,046 environmental surfaces (17.2%) and from 27 of 66 air samples (40.9%). During study week 14, VSE was recovered from 75 of the 124 surfaces sampled, representing 21.3% of all VSE-positive sites. A gentamicin-resistant VS Enterococcus faecium clone was recovered in high numbers from the air (>100 cfu/m(3)) and from surfaces throughout a 4-bed bay. The same clone was recovered from an adjacent isolation room as well. A total of 55 surfaces were contaminated with vancomycin-resistant enterococci (VRE). The environment of 2 isolated patients accounted for 85% of contaminated sites. Neither patient was known to be VRE-positive.
Conclusions:
Unrecognized colonization and/or the aerosolization of enterococci together with inadequate cleaning can lead to heavy, widespread, and persistent environmental contamination. All pose a significant risk for acquisition of antibiotic-resistant enterococci.
There is currently little evidence regarding potential risks of bacterial contamination of non-invasive ventilation (NIV) devices used by cystic fibrosis (CF) patients.
The aim of this study was to determine the extent of bacterial contamination of NIV devices in our regional adult CF centre.
Seven NIV devices recently used by CF patients chronically infected with Pseudomonas aeruginosa or Burkholderia cepacia complex (BCC) were swabbed in seven areas, both external and internal. Two devices had undergone ethylene oxide (EtO) sterilization between patient use and swabbing, and five devices had not undergone EtO sterilization.
Swabs from five devices had insignificant growth of environmental organisms and two devices had significant growth of environmental organisms. No CF pathogens were isolated from any machine.
No evidence was found of pathogenic microbial contamination of NIV devices used by CF patients in this small study. We suggest that further studies examine for evidence of bacterial contamination of NIV devices and that this issue should be included in future CF infection control guidelines.
Transport of infectious particles through the air has the potential to contaminate the indoor environment creating reservoirs of infectious material on surfaces. There is evidence that typical nursing activities can release large quantities of bacteria including MRSA into the hospital air, which may lead to surface contamination thereby increasing opportunities for further spread. Air sampling studies were conducted over a period of 5 days on a four-bed bay in a respiratory ward. Results showed that sampled bioaerosols are more likely to be carried on large particles >5 µm in diameter, and that the relationship between bioaerosols and particle size varies when respiratory interventions are in use. Increased activity in the hospital bay was shown to correlate to increased concentrations of bioaerosols whereas sedentary visitors did not. In particular, the occurrence of patient washing that occurred behind closed curtains correlated to large values of bioaerosol release. Floor cleaning generated large number of particles, but with no significant increase in sampled bioaerosols. This provides valuable information for understanding when and where bioaerosols are released on a hospital ward which may inform future research into physical segregation of patients and the definition of bioaerosol sources in computer simulations.
Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality associated with cystic fibrosis. For many years, the consensus was that cystic fibrosis patients acquire P. aeruginosa from the environment, and hence harbour their own individual clones. However, in the past 15 yrs the emergence of transmissible strains, in some cases associated with greater morbidity and increased antimicrobial resistance, has changed the way that many clinics treat their patients. Here we provide a summary of reported transmissible strains in the UK, other parts of Europe, Australia and North America. In particular, we discuss the prevalence, epidemiology, unusual genotypic and phenotypic features, and virulence of the most intensively studied transmissible strain, the Liverpool epidemic strain. We also discuss the clinical impact of transmissible strains, in particular the diagnostic and infection control approaches adopted to counter their spread. Genomic analysis carried out so far has provided little evidence that transmissibility is due to shared genetic characteristics between different strains. Previous experiences with transmissible strains should help us to learn lessons for the future. In particular, there is a clear need for strain surveillance if emerging problem strains are to be detected before they are widely transmitted.
Pseudomonas aeruginosa is the major pathogen in chronic lung infections of individuals with cystic fibrosis (CF). Unrelated CF patients may acquire P. aeruginosa from the environment or by cross-infection in the CF setting. We tested the efficacy of measures to prevent nosocomial acquisition of P. aeruginosa at a Paediatric CF centre in a prospective 10-year study. P. aeruginosa-positive and P. aeruginosa-negative patients were seen in alternating weeks at the outpatient clinic. Faucets were equipped with filters to prevent bacterial contamination of tap water. Serial isolates were collected since the first documentation of a P. aeruginosa-positive culture and genotyped with a multimarker microarray. During the 10-year study, the annual prevalence of patients with at least one P. aeruginosa-positive culture was 39±6% in a population of 149±12 patients. P. aeruginosa was detected for the first time in 54 patients of whom 11 patients became chronically colonised with P. aeruginosa. Transient colonisations were recorded 97 times. A nosocomial acquisition of P. aeruginosa at the CF centre probably happened in one case. The worldwide dominant clones in the global P. aeruginosa population were also the most abundant clones in the panel of 324 early CF isolates. No rare clone had expanded by nosocomial transmission. It can be concluded that cross-infection with P. aeruginosa was prevented with simple hygienic measures at a CF centre that had experienced local outbreaks of nosocomial spread among unrelated patients in the past.
Prior to modern typing methods, cross-infection of P. aeruginosa between people with cystic fibrosis (CF) was felt to be rare. Recently a number of studies have demonstrated the presence of clonal strains of P. aeruginosa infecting people with CF. The aim of this study was to determine whether strains of P. aeruginosa demonstrated differences in resistance to desiccation and whether preincubation in subminimum inhibitory concentrations (MICs) of β-lactam affected desiccation resistance. The experimental data were modelled to a first-order decay model and a Weibull decay model using least squares nonlinear regression. The Weibull model was the preferred model for the desiccation survival. The presence of a mucoid phenotype promoted desiccation survival. Preincubation with antibiotics did not have a consistent effect on the strains of P. aeruginosa. Meropenem reduced desiccation resistance, whereas ceftazidime had much less effect on the strains studied.
It is bewildering, in the face of so much evidence for the potential for cross-infection between patients – cross-infection that may have devastating consequences – that we continue to debate the advantages (numerous and important) and disadvantages (few and largely irrelevant) of keeping patients separated. Amazingly, to my mind, there has been no resolution of the conflicting points of view since Professor Geddes and I first argued this issue in a cystic fibrosis (CF) conference in 2001. Some CF centres have a strict patient segregation policy, some centres have no policy at all, and many centres follow management protocols that fall at varied points between these two extremes. In this paper I will provide evidence which I believe supports a strict segregation policy as practised in the Leeds CF centres.
During 2005-2007, we experienced sporadic isolations of multidrug-resistant (MDRP) Pseudomonas aeruginosa from wards in a general hospital in Hiroshima. The objective of this study was to analyze epidemiology relationships and the mode of spread of the strains.
Clonality was assessed using pulsed-field gel electrophoresis (PFGE) and serotyping. MICs were determined using the microdilution broth method. Investigations of the affected patients' movements and environmental sampling from the affected wards were conducted.
An abrupt increase in MDRP isolations began at the end of 2005 and ended in February 2007. A total of 25 MDRP strains were sporadically isolated from nine wards. Fourteen strains were genotypically and serologically identical. Analysis of the patients' movements identified that six of the 14 MDRP-positive patients became positive for MDRP when they were in the intensive care unit (ICU), and two became positive after the patients moved from the ICU to another nursing unit. Four MDRP strains were isolated from patients who did not stay in the ICU and were in ward E6, which had the second highest number of isolations. In July 2006, environmental sampling of the hospital identified a toilet brush in ward E6 that was contaminated with MDRP that was genotypically and serologically identical to the clinical isolates.
Our study suggests that the sporadic increase in MDRP isolates during 2005-2007 in the general hospital in Hiroshima was due to an epidemic of an MDRP clone. Continuity and spread of infection was probably due to cross infection and contamination in the hospital with the MDRP strain.
The objective of this study was to test the hypothesis that enhanced ultraviolet germicidal irradiation (eUVGI) installed in our neonatal intensive care unit (NICU) heating ventilation and air conditioning system (HVAC) would decrease HVAC and NICU environment microbes, tracheal colonization and ventilator-associated pneumonia (VAP).
The study was designed as a prospective interventional pre- and post-single-center study. University-affiliated Regional Perinatal Center NICU. Intubated patients in the NICU were evaluated for colonization, and a high-risk sub-population of infants <30 weeks gestation ventilated for ≥ 14 days was studied for VAP. eUVGI was installed in the NICU's remote HVACs. The HVACs, NICU environment and intubated patients' tracheas were cultured pre- and post-eUVGI for 12 months. The high-risk patients were studied for VAP (positive bacterial tracheal culture, increased ventilator support, worsening chest radiograph and ≥ 7 days of antibiotics).
Pseudomonas, Klebsiella, Serratia, Acinetobacter, Staphylococcus aureus and Coagulase-negative Staphylococcus species were cultured from all sites. eUVGI significantly decreased HVAC organisms (baseline 500,000 CFU cm(-2); P=0.015) and NICU environmental microbes (P<0.0001). Tracheal microbial loads decreased 45% (P=0.004), and fewer patients became colonized. VAP in the high-risk cohort fell from 74% (n=31) to 39% (n=18), P=0.04. VAP episodes per patient decreased (Control: 1.2 to eUVGI: 0.4; P=0.004), and antibiotic usage was 62% less (P=0.013).
eUVGI decreased HVAC microbial colonization and was associated with reduced NICU environment and tracheal microbial colonization. Significant reductions in VAP and antibiotic use were also associated with eUVGI in this single-center study. Large randomized multicenter trials are needed.
Exocrine pancreatic insufficiency and lung infection with Pseudomonas aeruginosa are major features of cystic fibrosis (CF). This monogenic disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. 267 children and adolescents with CF who were regularly seen at the same centre were assessed for an association of the CFTR mutation genotype with exocrine pancreatic function and the age of onset of chronic colonisation with P aeruginosa. The major mutation delta F508 accounted for 74% of CF alleles; 33 further CFTR mutations had been detected on the CF chromosomes of the study population by June, 1992. With the exception of delta F508/R347P compound heterozygotes, patients of the same mutation genotype were either pancreas insufficient (PI) or pancreas sufficient (PS). The age-specific colonisation rates with P aeruginosa were significantly lower in PS than in PI patients. The missense and splice site mutations that are "mild" CF alleles with respect to exocrine pancreatic function were also "low risk" alleles for the acquisition of P aeruginosa. On the other hand, the proportion of P aeruginosa-positive patients increased most rapidly in the PI delta F508 compound heterozygotes who were carrying a termination mutation in the nucleotide binding fold-encoding exons. Pancreatic status and the risk of chronic airways' colonisation with P aeruginosa are predisposed by the CFTR mutation genotype and can be differentiated by the type and location of the mutations in the CFTR gene.
Seventy-three environmental and clinical isolates of Pseudomonas aeruginosa recovered from a single hospital over a 6-month period were compared for epidemiological type characteristics. Environmental isolates were obtained from sinks, taps and water, in rooms where patients were treated. The strains represented only six O-antigenic types and 8.2% of them were not typable. Serotype 011 was most frequent in the environment, whereas serotypes 06, 012 and 02,5 predominated among clinical isolates. More than 60% of all isolates belonged to four pyocin types (1, 10, 33 and 45), and approximately 80% were phage typable. Environmental isolates were more sensitive to antibiotics than clinical isolates. There was little correspondence between the types of strains of P. aeruginosa isolated from patients and those isolated from the environment. However, isolates of identical type were frequently recovered from different patients within the same clinic and were found to be related in time and location. We conclude that the environment was not an important source of P. aeruginosa infection and that transfer of organisms was mainly from patient-to-patient.
The potential risk of spirometers in the transmission of respiratory infections has not been yet established. We performed a prospective cross-sectional study to determine the rate of colonization of a water-sealed spirometer and a pneumotachograph, and the potential risk of cross-transmission of microorganisms to patients using each of these devices. Fifty four patients (aged 51 +/- 18 (mean +/- SD) yrs) were included in the study. All of them had undergone forced spirometry with bronchodilator response by means of the water-sealed spirometer (n = 36) or the pneumotachograph (n = 18). None had a clinically apparent respiratory infection at the time of the study. Routine hygiene measures for respiratory equipment were performed before the study protocol. Samples for microbiological cultures of different parts both of the water-sealed spirometer (proximal and distal tubing, bell and water-bell) and pneumotachograph (proximal and distal tubing) were taken daily before and after the usual series of lung function tests during a 5 day period. Pharyngeal swab cultures were obtained before spirometry and 7 days later in each subject. Thirty six out of a total of 40 (90%) culture samples from the water-sealed spirometer showed microbial growth compared to 4 out of 30 (13%) samples obtained from the pneumotachograph (p < 0.0001). Significant colonization of the water-sealed spirometer was apparent after the third day of the study. The microorganisms most frequently isolated were penicillium sp. (62%), Pseudomonas fluorescens (32%), and Burkholderia cepacea (48%). Distal tubing, water and water-bell were the parts of the water-sealed spirometer that showed higher colonization counts (> or = 10(4) colony-forming units (cfu).mL-1). No transmission sequence of potentially pathogenic microorganisms from equipment to patients or vice versa could be demonstrated. In summary, the water-sealed spirometer frequently became colonized by microorganisms. The potential hazard of such equipment as reservoirs of microorganisms suggests a need for the implementation of new hygiene measures for their maintenance.
To assess the effect on clinical outcome of managing paediatric and adult patients with cystic fibrosis at specialised cystic fibrosis centres.
Cross sectional study.
Two adult cystic fibrosis centres in the United Kingdom.
Patients from an adult cystic fibrosis centre in Manchester were subdivided into those who had received continuous care from paediatric and adult cystic fibrosis centres (group A), and those who had received paediatric care in a centre not specialising in cystic fibrosis followed by adult care in a cystic fibrosis centre (group B). Group C were referrals to the new adult cystic fibrosis centre in Cambridge who had received neither paediatric nor adult centre care for their cystic fibrosis.
Body mass index (weight (kg)/height (m2)), lung function (forced expiratory volume in one second (FEV1 percentage of predicted)), the Northern chest x ray film score, and age at colonisation with Pseudomonas aeruginosa.
A prominent stepwise increase in body mass index was associated with increasing amounts of care at a cystic fibrosis centre; 18.3, 20.2, and 21.3 for groups C, B, and A respectively (P<0.001). Improved nutritional status was correlated with a higher FEV1 and better (lower) chest x ray film scores; r=0. 52 and -0.45 respectively (P<0.001 for both).
These findings provide the first direct evidence that management of cystic fibrosis in paediatric and adult cystic fibrosis centres results in a better clinical outcome, and strongly supports the provision of these specialist services.
Chronic respiratory infection by Pseudomonas aeruginosa is a significant determinant in the prognosis of cystic fibrosis patients. Cross-infection between cystic fibrosis patients and the prevalence of P. aeruginosa among them were investigated by microbiological surveillance and RAPD typing of the isolates. A total of 748 samples was cultured, including specimens from the respiratory tract (sputum or throat swabs) and hands of patients and medical staff, resulting in the collection of 86 isolates of P. aeruginosa from 65 samples. Prevalence of P. aeruginosa was 39.3% in respiratory samples, 0.2% on patients' hands and none in the medical staff's hand samples. RAPD typing characterised 51 genotypes and clonal persistence was observed in the majority of patients. These results suggest that cross-infection is not common in the outpatient clinic studied and a common source of acquisition is unlikely.
As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Project, we had the unique opportunity to study the longitudinal relationship between Pseudomonas aeruginosa (Pa) acquisition and infection and developing lung disease in children with CF. The primary objective was to determine whether acquisition of Pa was associated with a measurable change in the progression of lung disease. Two outcome measures were used to study 56 patients who were diagnosed through newborn screening: 1) Wisconsin additive chest radiograph score (WCXR), based on the average of scores from a pulmonologist and a radiologist, and 2) the highest forced expired volume in 1 sec (FEV(1))/forced vital capacity (FVC) ratio. We used two measures of Pa acquisition: 1) time of first positive protocol-determined oropharyngeal (with cough) culture, and 2) the magnitude of antibody titer detected by ELISA assays, using as antigen a crude cell lysate, purified exotoxin A, or an elastase toxoid prepared from three Pa strains. Other predictor variables included age, pancreatic status, height-for age, and weight-for-age-percentiles. The best regression model for predicting changes in the WCXR included time to first positive culture and antibody titer for Pa elastase. Prior to Pa acquisition, WCXR worsened by 0.45 points/year (P > 0.25); after Pa acquisition, the rate of worsening increased significantly (P < 0.001) to 1.40 points/year. Each antibody titer level (log base 2) increased the score by 0.48 points (P < 0.001). The best regression model for predicting change in the FEV(1)/FVC included only time to first positive culture. Prior to Pa acquisition, the FEV(1)/FVC ratio declined by 1.29%/year; after Pa infection, the rate of decrease significantly accelerated to 1.81%/year (P = 0.001). Our data show that Pa acquisition is associated with declining pulmonary status in children with CF, and that this effect is probably gradual rather than precipitous. Because these patients were diagnosed and treated aggressively, our estimates of the effects of Pa acquisition may be conservative. We also conclude that the WCXR appears to be more sensitive than FEV(1)/FVC in detecting early changes in lung disease associated with CF.
In the Gillies and Govan method of pyocin typing for Pseudomonas aeruginosa a cross-streaking technique was used, and 105 main types and 25 subtypes were identified by the patterns of inhibition observed on 13 indicator strains. Disadvantages of the technique included the need to remove test strain growth before application of the indicator strains, the 48-h period needed to obtain a result, and the inability to reliably type mucoid P. aeruginosa. Recent studies have enabled us to overcome these disadvantages and significantly improve the speed and application of pyocin typing. Our revised technique utilizes the same 13 indicator strains which are already used internationally. Test strains were rapidly applied to the surface of agar plates with a multiple inoculator. After incubation for 6 h and exposure to chloroform, the indicator strains were applied in agar overlays without prior removal of the test strain growth. After 18 h of incubation, the pyocin type was recognized by inhibition of particular indicator strains. Additionally, the activity of particulate (R and F) and nonparticulate (S) pyocins could be distinguished on the basis of inhibition zone size, which thus allowed further discrimination. The revised technique allows typing within 24 h, increases the number of identifiable types, and can be used to type mucoid strains.
Genotyping and antibiotic susceptibility testing were used to analyze Pseudomonas aeruginosa and Burkholderia cepacia strains from sink drain from 14 pediatric patients with cystic fibrosis (CF) and from hospital personnel as part of a 4 week prospective study of strain transmission in a pediatric ward. A total of 87.5% of all washbasin drains were contaminated with P. aeruginosa [102 to 105 colony forming units (CFU)/ml sink fluid], whereas B. cepacia was found only once in a sink drain. From the eight CF patients already infected with P. aeruginosa upon entering the ward, we isolated six genotypes that were identical with strains found in sink drains of the ward. Four of the 16 members of the personnel had one positive P. aeruginosa hand culture. B. cepacia was never found in patients or on personnel hands. Hand washing in contaminated sinks (≥ 103 CFU/ml) led to positive P. aeruginosa or B. cepacia hand cultures. P. aeruginosa or B. cepacia embedded in sputum were transmissable by hand shaking for up to 180 min, whereas both pathogens suspended in physiological saline were transmissable to other hands only up to 30 min. Genotyping of P. aeruginosa revealed strain transmission from CF patients or the environment to other patients or the personnel, as well as one transmission from the environment to a CF patient. The ability of CF sputum to prolong survival of P. aeruginosa and B. cepacia may be important for strain transmission. The results suggest that improved hygienic measures are required to prevent routes of bacterial transmission via the hands and sink drains. Pediatr Pulmonol. 1996; 21:90–100. © 1996 Wiley-Liss, Inc.
In order to identify the possible reservoirs and routes of cross-infection with Pseudomonas aeruginosa, samples from patients, staff, and the environment of a cystic fibrosis centre and two control wards at an infectious disease clinic were collected during a two-week period in 1980. All the Ps. aeruginosa strains were phage and serotyped. Ps. aeruginosa was isolated from 90 (51%) of the cystic fibrosis patients and most belonged to the 0-3/9 complex, characteristic of strains from patients in the centre. Some of the patients were able to spread Ps. aeruginosa into the air and to their hands by coughing, and Ps. aeruginosa in dried sputum could survive for at least one week. Strains of the same epidemiological types as found in the cystic fibrosis patients were isolated from sinks, soap, baths, toys, tables, brushes, cloths, and air in the clinic. In contrast, Ps. aeruginosa of the same epidemiological types were only found in a few of the sinks in one of the control wards where a few cystic fibrosis patients were regularly treated in isolation cubicles. The precautions employed to prevent future cross-infection include segregation of Ps. aeruginosa-infected from non-infected patients in separate wards and arranging for visits on separate days in the out-patients clinic. The survival of cystic fibrosis patients treated in the centre is much longer than those treated outside the centre despite the problems of cross-infection.
The environment of two hospitals was examined in order to determine the level of contamination with Pseudomonas œruginosa. It was found that certain objects such as sink-traps, floor-cloths, dishcloths, and mops were frequently contaminated with Ps. œruginosa (85/154 samples yielded positive cultures). On the other hand, when similar areas were examined in domestic homes Ps. œruginosa was rarely isolated.
To evaluate the relationship between Pseudomonas aeruginosa colonization and the development of lung disease, we studied 895 patients who attended our cystic fibrosis clinic between 1975 and 1988. The prevalence of P. aeruginosa colonization was 82%. Patients who acquired P. aeruginosa in the first year of life had a similar 10-year survival rate (85%) to that in patients who were colonized between the ages of 1 and 7 years (87%), and to that in patients colonized after the age of 7 years (78%). One year before colonization, mean age, forced expiratory volume in 1 second (FEV1), forced vital capacity, and forced expiratory flow in the mid-expiratory phase were similar to those in a group of patients who remained free of P. aeruginosa. No significant change in pulmonary function variables could be demonstrated 1 year and 2 years after the colonization. The rate and duration of hospitalization did not increase in the years after P. aeruginosa colonization compared with the years before colonization. By the age of 7 years, the mean percentage of predicted FEV1 was lower by 10% in patients who were already colonized by P. aeruginosa compared with those who were not colonized (p less than 0.01). A similar reduction in FEV1 was observed at all ages from 7 to 35 years, but no precipitate rate of decline in FEV1 could be associated with P. aeruginosa colonization. We conclude that although P. aeruginosa colonization is associated with 10% lower lung function, it does not cause an immediate and rapid reduction, as has been previously reported. The clinical course and the pulmonary deterioration in cystic fibrosis after P. aeruginosa colonization is a gradual and variable process.
Pseudomonas aeruginosa colonizes the respiratory tract of most older patients with cystic fibrosis. The means by which these bacteria are acquired and the risk for patient-to-patient spread among subjects with cystic fibrosis are poorly understood. We studied the spread of Ps. aeruginosa within a hospital environment. Pseudomonas was rarely recovered from the inanimate environment surrounding patients with cystic fibrosis or from hand or rectal cultures of patients who were colonized in the oropharynx. There was transient cross-colonization with Ps. aeruginosa between patients with cystic fibrosis sharing a hospital room in three of seven pairs studied. In all cases the "new" isolate was recoverable only once and was not found during a 2-year follow-up. Three of four sibling pairs with cystic fibrosis shared the same Ps. aeruginosa serotype(s). The risk of sustained cross-colonization by Ps. aeruginosa between patients with cystic fibrosis appears to be minimal, except under conditions of prolonged close contact.
The epidemiology of Pseudomonas aeruginosa infection at a cystic fibrosis (CF) center was monitored over a 3-year period. A total of 835 isolates from 72 unrelated patients and 22 siblings with CF were analyzed by genome fingerprinting and serotyping, bacteriophage typing, and pyocin typing. For genome fingerprinting, bacterial chromosomes were digested with one of the restriction endonucleases SpeI, DraI, XbaI, SspI, and NheI, which cut only rarely, and subsequently separated by field inversion gel electrophoresis. The physical genome analysis allowed us to classify P. aeruginosa strains in terms of DNA relatedness. Related strains differed by fewer than six DraI bands in the fingerprint, whereas unrelated strains differed by more than 20 DraI bands. All unrelated CF patients were colonized with different strains. The absence of a nosocomial spread of organisms at the CF center was attributed to the strict hygiene measures observed at the hospital. CF siblings were harboring either identical or closely related strains; transmission within the family is thought to be the most likely cause.
Pseudomonas aeruginosa was isolated from sink waste-traps in 27 of 116 (23.3%) samples from a large general hospital and from 19 of 47 (40.4%) samples from a burns unit at another hospital. Smaller proportions of samples from sink outlets and surfaces of basins yielded Ps. aeruginosa. A waste-trap heater ('Econa') used twice daily for fifteen minutes reduced the isolations of Ps. oeruginosa from waste-traps to a very low level; isolations of other organisms were also reduced, though to a smaller extent. Despite the continuing high frequency of Ps. aeruginosa in sinks and some other moist hospital sites, Ps. aeruginosa infections were infrequent in the general hospital and had been greatly reduced by the successful use of various prophylactic measures in the burns unit.
Nine hundred sixteen cultures were obtained from homes of patients with cystic fibrosis, control homes, salad bars, and food markets, and analyzed for the presence of Pseudomonas cepacia and related bacteria. P cepacia was recovered from 5 (18%) of 27 homes, and from 20 (4%) of 509 cultures collected outside of homes. Relative to other pseudomonads, P cepacia is found infrequently in the environment. It is not clear how frequently these sources contribute to acquisition of this bacteria by persons with cystic fibrosis.
In order to identify the possible reservoirs and routes of cross-infection with Pseudomonas aeruginosa, samples were collected during a six-week period in autumn 1992 from patients, their visiting parents, staff and the inanimate environment of the Danish Cystic Fibrosis (CF) Centre and from a control ward with common paediatric diseases. All the P. aeruginosa strains were phage typed and serotyped. From 240 CF patients, 310 strains of P. aeruginosa were isolated, and of these 283 (91.3%) belonged to the polyagglutinable phenotype, most often with a short phage type (31/188 or 109). P. aeruginosa was isolated from only six (0.6%) of 1000 swabs taken from the environment. These six environmental strains and 20 P. aeruginosa strains from CF patients with identical serotype and phage type were examined with pulsed field gel electrophoresis. None of the patients harboured strains similar to the environmental strains, indicating the present isolation procedure and hygienic precautions were effective in our CF centre, and prevented contamination of the environment with P. aeruginosa.
Background:
Pseudomonas aeruginosa colonisation of the airways of patients with cystic fibrosis (CF) is associated with considerable respiratory morbidity. Although segregation of colonised patients from non-colonised patients to prevent cross-infection has been recommended, there is little evidence that such cross-infection is widespread. We observed that a high proportion of children attending our CF clinic were colonised with P aeruginosa that was resistant to ceftazidime and other beta-lactam antibiotics. We used two genomic fingerprinting techniques to see whether this may have arisen from epidemic spread of a single strain.
Methods:
The prevalence of P aeruginosa colonisation and the antibiotic susceptibility of the organisms was determined from review of laboratory reports in the case-notes of 120 children with CF. Isolates were cultured from the sputum of 65 children colonised with ceftazidime-resistant P aeruginosa. Polymorphisms in total bacterial DNA from 92 isolates were analysed with two molecular fingerprinting techniques--pulsed-field gel electrophoresis after restriction enzyme digestion and assessment of flagellin gene polymorphisms by amplification of the whole gene and restriction enzyme digestion.
Results:
92 (76.7%) of 120 children were colonised with P aeruginosa, and 65 of the 92 harboured isolates that were resistant to ceftazidime. Only three of the 92 children had never been treated with ceftazidime. The results of the two molecular-fingerprinting techniques were concordant and showed that 55 of 65 children harboured the same epidemic strain. This strain was resistant to ceftazidime, azlocillin, and imipenem, and sensitive to tobramycin and ciprofloxacin.
Interpretation:
This study provides the first molecular evidence of a long-term outbreak of P aeruginosa in a CF centre. We suggest that careful surveillance of the prevalence of antibiotic resistance in CF centres should be instituted with measures to prevent cross-infection. We believe that antipseudomonal monotherapy should be considered with caution.
Inhalation of aerosols contaminated with gram-negative bacteria generated from home-use nebulizers used by cystic fibrosis (CF) patients may be a primary route for bacterial colonization of the lung. Burkholderia cepacia was isolated from 3 of [corrected] 35 home-use nebulizers, and Stenotrophomonas maltophilia was isolated from 4 of 35 home-use nebulizers. Sputum cultures for two patients whose nebulizers were contaminated with B. cepacia did not yield the organism. However, DNA macrorestriction analysis by pulsed-field gel electrophoresis confirmed that one of two strains of B. cepacia recovered from the nebulizer of a third patient was also present in the sputum of that patient. Although Pseudomonas aeruginosa was isolated from 34 patients, none of the nebulizers were positive for the organism. Sixty-nine percent of nebulizers were contaminated, and up to 16 different environmental colistin-resistant, gram-negative species were identified. The heaviest contamination was found beneath the chamber atomizer. A questionnaire survey showed that the majority of patients (28 of 34) were receiving nebulized colistin and/or gentamicin. Patients who followed recommended instructions for good nebulizer hygienic practice and paid particular attention to drying had minimal or no contamination of their nebulizers.
Many reports have shown bacterial contamination of nebulizers used by patients with cystic fibrosis (CF) at home. At the Stockholm CF centre we recommend dismantling the equipment, washing, rinsing and drying it after each use, and disinfecting it once daily by boiling water or by 2% acetic acid followed by drying without rinsing. We studied whether patients comply with these recommendations and whether they are sufficient to prevent bacterial contamination. Nebulizers from 49 CF patients were investigated, 21 of whom are chronically colonized with Pseudomonas aeruginosa and one with Burkholderia cepacia. All patients were visited at home. Thirty-nine patients (79%) disinfected their equipment after the latest use in accordance with our recommendations. Thirty-eight pieces showed no, or only scanty, growth of micro-organisms belonging to the normal oropharyngeal flora. A moderate growth of alpha-streptococci was observed from a further five pieces. Four of these had not been cleaned after the latest inhalation occasion, and one was visibly dirty. Pseudomonads were observed from three pieces; two of these had been disinfected by boiling water and one by acetic acid, followed by rinsing in tap water. All three had been inadequately dried. Pseudomonads could not be cultured simultaneously from the sputum of these three patients. In conclusion, most patients comply with our cleaning and disinfection recommendations and these recommendations appear satisfactory in preventing bacterial contamination.
Twenty-seven patients with cystic fibrosis from our Danish Cystic Fibrosis Center went to a winter camp for 1 week in November of 1990. This study is based on 22 of these patients. Prior to attending camp, 17 out of 22 patients harbored Pseudomonas aeruginosa in their sputum, but 5 patients did not. After returning from camp, all 22 patients harbored P. aeruginosa in the sputum, including the 5 patients whose sputum was free of P. aeruginosa before they went. Epidemiological typing used pulsed-field gel electrophoresis of the P. aeruginosa isolates was performed. The typing results showed that the 5 cystic fibrosis patients who were free of P. aeruginosa in their sputum prior to the winter camp had acquired P. aeruginosa isolates identical to the P. aeruginosa strains isolated from the other 17 cystic fibrosis patients. This constitutes a cross-colonization rate of 100%, the highest rate ever detected among patients with cystic fibrosis. We conclude that separate holiday camps based on the infection status of the patients with cystic fibrosis are necessary to avoid cross-infection of patients not infected with P. aeruginosa.
A study on the molecular epidemiology of Pseudomonas aeruginosa in patients with cystic fibrosis (CF) from Germany (N = 18) and Israel (N = 12) is presented. The aim is to provide an answer to the question as to whether or not social contact outside the hospital environment involves a potential risk for person-to-person spread of this pathogen.
Sputa from German and Israeli patients were obtained while these were attending a holiday camp in Israel. The sputum samples were analysed with regard to Pseudomonas aeruginosa. Strains dissimilar in macroscopic appearance and/or antibiotic resistance patterns were genotyped using pulsed-field gel electrophoresis after digestion of genomic DNA with restriction endonuclease Spel. The genetic polymorphism of DNA fragment patterns of all strains (N = 146) was studied for their overall relatedness using a fingerprint software system.
Most of the German patients (77.7%) were colonised persistently by a unique clonal type during the four-week screening period. Isolates obtained from Israeli patients displayed a very close clonal relationship and a higher antibiotic resistance as a result of preceding epidemic spread of certain clones before the camp. Additionally, isolates showing identical PFGE patterns were demonstrated once in a single male Israeli patient and in one female German patient, suggesting previous cross-colonisation.
The occurrence of person-to-person spread through social contact in patients with CF is supported by our findings, but remains a rare event outside the hospital environment, provided appropriate hygienic measures are applied.
We initiated a prospective surveillance study to investigate possible Pseudomonas aeruginosa cross-infection in our cystic fibrosis centre. We characterised isolates by pyocin typing and pulsed-field gel electrophoresis. 22 (14%) of 154 patients with chronic P aeruginosa had isolates with similar and new pyocin and pulsed-field gel electrophoresis types. The shared isolates showed unusual phenotypic features: they were non-pigmented, non-motile, and resistant to a number of antipseudomonal antibiotics. Cross-infection by a multiresistant P aeruginosa strain has therefore occurred in patients attending our cystic fibrosis centre. We recommend microbiological surveillance in other cystic fibrosis centres.
Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) is preceded by a period of colonization and acute infection. Early aggressive antibiotic treatment of initial colonisation may prevent or at least delay chronic pulmonary infection. We initiated treatment with a combination of IV β‐lactam tobramycin, followed by nebulized colistin when PA was first isolated from patients with CF. Subsequent serial PA isolates obtained from these colonized CF patients were characterized by means of molecular methods to determine whether they were genetically related to the initial strain.
Initial colonization was eradicated in all 19 patients. All patients reacquired PA within 3–25 months during the 3 years of follow‐up. Fourteen patients acquired a new PA strain with a distinct genotypic profile, suggesting a new source of contamination. Five patients had two PA isolates with identical genotypes, suggesting either previous undetected respiratory tract colonization or a persistent environmental source of contamination. Pediatr Pulmonol. 2001; 32:288–292. © 2001 Wiley‐Liss, Inc.