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Bacteremic Pseudomonas pneumonia
Purpose of review:
As Streptococcus pneumoniae was considered the etiological agent of nearly all the cases of pneumonia at the beginning of the 20th century, and today is identified in fewer than 10-15% of cases, we analyze the possible causes of such a decline.
Recent findings:
Extensive use of early empiric antimicrobial therapy, discovery of previously unrecognized pathogens, availability to newer diagnostic methods for the recognition of the pneumonia pathogens (PCR, urinary antigens, monoclonal antibodies etc.) and of improved preventive measures, including vaccines, are some of possible explanations of the declining role of S. pneumoniae in the cause of pneumonia.
Summary:
The 14-valent and the 23-valent capsular polysaccharide pneumococcal vaccines were licensed in 1977 and 1983, respectively. The seven-valent protein-conjugated capsular polysaccharide vaccine, approved for routine use in children starting at 2 months of age, was highly effective in preventing invasive pneumococcal disease in children but also in adults because of the herd effect. In 2010, the 13-valent protein-conjugated capsular polysaccharide vaccine replaced seven-valent protein-conjugated capsular polysaccharide vaccine. With the use of conjugated vaccines, a decrease of the vaccine-type invasive pneumococcal disease for all age groups was observed. Both the direct effect of the vaccine and the so-called herd immunity are considered responsible for much of the decline.
Acinetobacter baumannii has been a dreadful problem for ICU physicians for a long time. Bacteremic pneumonia (BP) caused by this organism has a higher mortality compared to other organisms. Between 2012 and 2015, 86 BP and 89 non-bacteremic pneumonia (NBP) patients from five ICUs were enrolled into the study. The 7-day and 14-day mortality rates were higher in BP patients than in NBP patients (P < 0.001). Procalcitonin elevation, high APACHEII score and recent surgery, were independently associated with BP episodes. Acute respiratory distress syndrome, coma, high APACHEII score and procalcitonin elevation, were independently associated with mortality in the BP group. Extensively drug-resistant isolates were detected in 34.9% of BP and 25.8% of NBP isolates. PFGE identified 12 and 9 genotypes in the BP and NBP isolates, respectively, with 6 genotypes shared by both groups. ST195 was the most prevalent type (40%), followed by ST457 (18.9%). The pandemic clonal complex 92 was predominant, accounting for 94.3% of the strains. For all studied periods, mortality remained higher in the BP than the NBP group. Disease severity was the main risk factor for high mortality in the BP group, and other factors related to mortality were infection, and not treatment or microbiology-related.
A single dose of pegfilgrastim or the daily administration of colony-stimulating factors can be used to prevent febrile neutropenia. This may delay the detection of rapidly progressive infections among cancer patients undergoing chemotherapy. We report a case of Pseudomonas aeruginosa bacteremic pneumonia that occurred in a patient receiving pegfilgrastim.
In Osler’s time, bacterial pneumonia was a dreaded event, so important that he borrowed John Bunyan’s characterization of tuberculosis and anointed the pneumococcus, as the prime pathogen, “Captain of the men of death” 1.One hundred years later much has changed, but much remains the same. Pneumonia is now the sixth most common cause of death and the most common lethal infection in the United States. Hospital-acquired pneumonia is now the second most common nosocomial infection.2 It was documented as a complication in 0.6% of patients in a national surveillance study,3 and has been reported in as many as 20% of patients in critical care units.4,5 Furthermore, it is the leading cause of death among nosocomial infections.6 Leu and colleagues7 were able to associate one-third of the mortality in patients with nosocomial pneumonia to the infection itself. The increase in hospital stay, which averaged 7 days, was statistically significant. It has been estimated that nosocomial pneumonia produces costs in excess of $500 million each year in the United States, largely related to the increased length of hospital stay.
Bacterial infection of the lung has represented a serious health problem throughout medical history. Although briefly looked on with some complacency during the early antibiotic era, bacterial pneumonia has now resumed its deadly position in hospitalized patients.1,2 Factors that have contributed to this resurgence of disease include changes in human bacterial flora,3 the discovery of previously unrecognized organisms,4 and the widespread use of immunosuppressive therapy.5 Changes in the clinical spectrum of pneumonia have also resulted from alterations in the inherent virulence of certain microorganisms and from changes in human susceptibility to antimicrobial agents.
Pseudomonas aeruginosa is an organism of relatively low virulence that rarely affects those with intact host defenses. In the immunocompromised host, however, it is capable of using a wide array of potential virulence factors to cause a variety of serious infections. P. aeruginosa (formerly Bacillus pyocyaneus) was originally isolated in pure culture by a French pharmacist named Gessard in 1882.1 The organism is ubiquitous in nature, has minimal growth requirements, is nutritionally versatile, and thrives in moist environments.2
In Osier’s time, bacterial pneumonia was a dreaded event, so important that he borrowed John Bunyan’s characterization of tuberculosis and anointed the pneumococcus, as the prime pathogen, “Captain of the men of death.”1 One hundred years later much has changed, but much remains the same. Pneumonia is now the sixth most common cause of death and the most common lethal infection in the United States. Hospital-acquired pneumonia is now the second most common nosocomial infection.2 It was documented as a complication in 0.6% of patients in a national surveillance study,3 and has been reported in as many as 20% of patients in critical care units.4 Furthermore, it is the leading cause of death among nosocomial infections.5 Leu and colleagues6 were able to associate one third of the mortality in patients with nosocomial pneumonia to the infection itself. The increase in hospital stay, which averaged 7 days, was statistically significant. It has been estimated that nosocomial pneumonia produces costs in excess of $500 million each year in the United States, largely related to the increased length of hospital stay.
An einem Meerschweinchenmodell der experimentellenPseudomonas aeruginosa-Pneumonie wurden die Faktoren untersucht, die die Wirksamkeit einer passiven Immunisierung mit Psomaglobin®N*, einem i.v.Pseudomonas-Immunglobulin, beeinflussen. Tiere, die 2 Stunden nach Infektion mit einer einmaligen intravenösen Infusion von Psomaglobin®N in einer Dosis von 500 mg/kg behandelt wurden, wiesen eine Überlebensrate von 33% auf. Geringere Dosen waren weniger wirksam. Keines der mit Albumin behandelten Kontrolltiere überlebte. Die Therapie mit Psomaglobin®N war wirksam, wenn sie 2 Stunden oder 8 Stunden nach der Infektion einsetzte. Begann sie erst 24 Stunden nach der Infektion, so zeigte sie dagegen keine Wirkung mehr. Neutropenische Tiere (vorangegangene Cyclophosphamid-Behandlung) überlebten nach alleiniger Behandlung mit Psomaglobin®N nicht. Bei kombinierter Therapie mit Psomaglobin®N und Tobramycin stieg die Überlebensrate im Vergleich zu einer alleinigen Tobramycin-Behandlung jedoch signifikant auf 86% gegenüber 43% (pP. aeruginosa-Pneumonie sein könnte.
Hospital-acquired pneumonia is associated with high rates of morbidity and mortality, and dissemination to the bloodstream is a recognized risk factor for particularly poor outcomes. Yet the mechanism by which bacteria in the lungs gain access to the bloodstream remains poorly understood. In this study, we used a mouse model of Pseudomonas aeruginosa pneumonia to examine this mechanism. P. aeruginosa uses a type III secretion system to deliver effector proteins such as ExoS directly into the cytosol of eukaryotic cells. ExoS, a bi-functional GTPase activating protein (GAP) and ADP-ribosyltransferase (ADPRT), inhibits phagocytosis during pneumonia but has also been linked to a higher incidence of dissemination to the bloodstream. We used a novel imaging methodology to identify ExoS intoxicated cells during pneumonia and found that ExoS is injected into not only leukocytes but also epithelial cells. Phagocytic cells, primarily neutrophils, were targeted for injection with ExoS early during infection, but type I pneumocytes became increasingly injected at later time points. Interestingly, injection of these pneumocytes did not occur randomly but rather in discrete regions, which we designate "fields of cell injection" (FOCI). These FOCI increased in size as the infection progressed and contained dead type I pneumocytes. Both of these phenotypes were attenuated in infections caused by bacteria secreting ADPRT-deficient ExoS, indicating that FOCI growth and type I pneumocyte death were dependent on the ADPRT activity of ExoS. During the course of infection, increased FOCI size was associated with enhanced disruption of the pulmonary-vascular barrier and increased bacterial dissemination into the blood, both of which were also dependent on the ADPRT activity of ExoS. We conclude that the ADPRT activity of ExoS acts upon type I pneumocytes to disrupt the pulmonary-vascular barrier during P. aeruginosa pneumonia, leading to bacterial dissemination.
Fifteen noninfected patients received three consecutive doses of tobramycin (1.7 mg/kg intramuscularly). Serum and bronchial secretions were obtained during bronchoscopy. Microbiologic assay demonstrated that bronchial secretions containing tobramycin produced inappropriateT obramycin is a relatively new aminoglycoside antibiotic which has properties similar in many respects to gentamicin.”2 However, the major advantage of tobramycin over gentamicin is its greater in vitro activity against Pseudomonas aeruginosa.3’4 This important property may be particularly useful in the treatment of Pseudomonas pneumonias which have been reported to produce mortality rates of up to 100 percent even in the presence of appropriate
Objective:
To compare pulmonary high-resolution CT (HRCT) findings in patients with Pseudomonas aeruginosa pneumonia to HRCT findings in patients with Cytomegalovirus (CMV) pneumonia.
Methods:
We studied 124 patients (77 men, 47 women; age range, 20-89 years; mean age, 65.4 years) with P. aeruginosa pneumonia and 44 patients (22 men, 22 women; age range, 36-86 years; mean age, 63.2 years) with CMV pneumonia.
Results:
CT findings of consolidation (p < 0.005), bronchial wall thickening (p < 0.001), cavity (p < 0.05), and pleural effusion (p < 0.001) were significantly more frequent in patients with P. aeruginosa pneumonia than in those with CMV pneumonia. Centrilobular nodules, a crazy-paving appearance, and nodules were significantly more frequent in patients with CMV pneumonia than in those with P. aeruginosa pneumonia (all p < 0.001).
Conclusion:
Pulmonary HRCT findings, such as bronchial wall thickening, crazy-paving appearance, and nodules may be useful in distinguishing between P. aeruginosa pneumonia and CMV pneumonia.
Key points:
Distinguishing Pseudomonas aeruginosa pneumonia from Cytomegalovirus pneumonia is important. Characteristic features of underlying conditions are present in each pneumonia species. Bronchial wall thickening and cavities are more frequent in Pseudomonas aeruginosa pneumonia. Nodules and a crazy-paving appearance are more frequent in Cytomegalovirus pneumonia.
A human immunoglobulin G preparation, enriched in type-specific antibodies against Pseudomones aeruginosa lipopolysaccharide immunotypes 1, 2, 4, 6 (Fisher scheme), and suitable for intravenous infusion, has recently been developed. We evaluated the therapeutic efficacy of this preparation in a guinea pig model of P aeruginosa pneumonia. Intravenous infusion of 500 mg/kg of hyperimmune globulin into guinea pigs produced elevations in serum antibodies against P aeruginosa , which persisted for one week or longer. For study, animals were infected with type 1 or type 4 P aeruginosa challenge strains, then treated two hours after infection with a single intravenous infusion of 5% hyperimmune globulin (500 mg/kg), or 5% albumin. Cumulative survival rates for type 1 infection were 0/33 controls, and 12/36 globulin ( P P P aeruginosa immunoglobulin G preparation was more efficacious in treating pneumonia than was a conventional (nonhyperimmune) immunoglobulin G preparation. Finally, in experiments combining hyperimmune P aeruginosa globulin with tobramycin (1.7 mg/kg, six hours and 24 hours after infection), cumulative survivals from pneumonia were increased to 87%, as compared to survivals of 50% for tobramycin alone, 25% for globulin alone, and 0% in control groups. We conclude that passive immunization with a recently developed hyperimmune P aeruginosa immunoglobulin G preparation may be therapeutically useful in the management of life-threatening P aeruginosa pneumonia.
The current circumstances associated with Pseudomonas aeruginosa bacteremia are reviewed in 108 episodes to assess the impact of new antimicrobial drugs on this infection. Since 1961, Pseudomonas bacteremia has apparently become more frequent with proportional increases in middle-aged patients. The respiratory tract has become the major source of infection. Clinical features are not characteristic, but infected patients are almost uniformly severely ill before blood stream invasion occurs. The use of gentamicin, carbenicillin and colistin has not changed the outcome of Pseudomonas bacteremia. Although better than no anti-microbial treatment, these drugs cannot be shown to be superior to any other available antibiotics. A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias. In view of the poor results with antibiotics, investigation into immunologic prophylaxis and therapy is needed. At the present time, control of the patients' underlying disease contributes most towards assuring survival with Pseudomonas bacteremia.
Objective:
The aim of this study was to assess clinical and pulmonary thin-section CT findings in patients with acute Pseudomonas aeruginosa (PA) pulmonary infection.
Methods:
We retrospectively identified 44 patients with acute PA pneumonia who had undergone chest thin-section CT examinations between January 2004 and December 2010. We excluded nine patients with concurrent infections. The final study group comprised 35 patients (21 males, 14 females; age range 30-89 years, mean age 66.9 years) with PA pneumonia. The patients' clinical findings were assessed. Parenchymal abnormalities, enlarged lymph nodes and pleural effusion were evaluated on thin-section CT.
Results:
Underlying diseases included malignancy (n=13), a smoking habit (n=11) and cardiac disease (n=8). CT scans of all patients revealed abnormal findings, including ground-glass opacity (n=34), bronchial wall thickening (n=31), consolidation (n=23) and cavities (n=5). Pleural effusion was found in 15 patients.
Conclusion:
PA pulmonary infection was observed in patients with underlying diseases such as malignancy or a smoking habit. The CT findings in patients with PA consisted mainly of ground-glass attenuation and bronchial wall thickening.
Advances in knowledge:
The CT findings consisted mainly of ground-glass attenuation, bronchial wall thickening and cavities. These findings in patients with an underlying disease such as malignancy or a smoking habit may be suggestive of pneumonia caused by PA infection.
Pseudomonas aeruginosa is an uncommon cause of community-acquired pneumonia (CAP), but a common cause of hospital-acquired pneumonia. Controversies exist for diagnostic methods and antibiotic therapy. We review the epidemiology of CAP, including that in patients with HIV and also in hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP) and bronchoscope-associated pneumonia. We performed a literature review of clinical studies involving P aeruginosa pneumonia with an emphasis on treatment and prevention. Pneumonia due to P aeruginosa occurs in several distinct syndromes: (1) CAP, usually in patients with chronic lung disease; (2) hospital-acquired pneumonia, usually occurring in the ICU; and (3) bacteremic P aeruginosa pneumonia, usually in the neutropenic host. Radiologic manifestations are nonspecific. Colonization with P aeruginosa in COPD and in hospitalized patients is a well established phenomenon such that treatment based on respiratory tract cultures may lead to overtreatment. We present circumstantial evidence that the incidence of P aeruginosa has been overestimated for hospital-acquired pneumonia and reflex administration of empirical antipseudomonal antibiotic therapy may be unnecessary. A diagnostic approach with BAL and protected specimen brush using quantitative cultures for patients with VAP led to a decrease in broad-spectrum antibiotic use and improved outcome. Endotracheal aspirate cultures with quantitative counts are commonly used, but validation is lacking. An empirical approach using the Clinical Pulmonary Infection Score is a pragmatic approach that minimizes antibiotic resistance and leads to decreased mortality in patients in the ICU. The source of the P aeruginosa may be endogenous (from respiratory or GI tract colonization) or exogenous from tap water in hospital-acquired pneumonia. The latter source is amenable to preventive measures.
The effects of the combination of a murine monoclonal antibody (MAb) specific for the O side chain of Pseudomonas aeruginosa Fisher immunotype 1 lipopolysaccharide and sparfloxacin in a neutropenic mouse model of P. aeruginosa pneumonia were examined. Under the condition that neither MAb at a dose of 500 micrograms per mouse administered intravenously nor a suboptimal dose of oral sparfloxacin (5 mg/kg of body weight) protected mice from challenge with a fatal dose, the combination therapy with MAb and sparfloxacin caused a significant increase in the survival rate (P less than 0.001 compared with either treatment alone). The effect of the combination was closely correlated to bacterial killing in plasma and lung tissue of infected mice. In vitro, a significant MAb-dependent, complement-mediated killing of P. aeruginosa was documented in the presence of sparfloxacin at one-half the MIC, while the killing was not observed in the absence of sparfloxacin. These in vivo and in vitro data suggest the usefulness of combination therapy with a lipopolysaccharide-reactive immunoglobulin G MAb and sparfloxacin in neutropenic patients with P. aeruginosa pneumonia.
We identified and reviewed retrospectively all the cases of infection by Pseudomonas and related genera in patients with AIDS and AIDS-related complex (ARC) who were hospitalized at our Institution over a 36-month period. We recorded 48 episodes of infection in 34 of 355 patients with AIDS, and in two of 73 patients with ARC: 25 pneumonias (9 community-acquired and 16 of nosocomial origin). 20 urinary tract infections, two soft tissue infections and one sepsis. In 14 of 16 patients with nosocomial pneumonia but in only one of nine patients with community-acquired pneumonia did we find coexisting opportunistic lung diseases. The following micro-organisms were isolated: P. aeruginosa in 41 cases, P. fluorescens in three cases, Xanthomonas maltophilia (P. maltophilia) in two cases, P. putida in one case. Comamonas testosteronis (P. testosteronis) and Comamonas acidovorans (P. acidovorans) in one case. Amikacin and ceftazidime, alone or in combination, appear to be the optimal choice of therapy for severe Pseudomonas infections in HIV-infected patients, although in our study six of 47 isolates were resistant in vitro to amikacin, and nine of 31 isolates were resistant to ceftazidime.
We reviewed the records of all patients in the intensive care unit (ICU) who had Pseudomonas aeruginosa pneumonia over a 2.5-year period. Of patients with P aeruginosa pneumonia, 20 of 34 survived the initial episode of pneumonia. Ten of these 20 developed recurrence. In the nonrecurrent group, nine of ten survived hospitalization, compared to only four of ten in the recurrent group. Comparing the recurrent to the nonrecurrent group, factors associated with recurrence were the APACHE 2 score (12.3 +/- 2.7 vs 8.6 +/- 4.2 [p less than 0.03]), APS score (7.0 +/- 3.5 vs 2.7 +/- 2.1 [p less than 0.01]), and chronic pulmonary disease (8/10 vs 2/10 [p less than 0.05]). The recurrent P aeruginosa group was younger (63 +/- 10 vs 74 +/- 11 years old [p less than 0.03]) and spent more time receiving mechanical ventilation (95 +/- 64 vs 26 +/- 36 days [p less than 0.01]), in the ICU (101 +/- 61 vs 33 +/- 35 days [p less than 0.01]), and in the hospital (144 +/- 77 vs 84 +/- 32 days [p less than 0.03]). Although not statistically significant, in the recurrent group, eight of ten patients had tracheostomy and seven of ten had COPD, vs three of ten and two of ten, respectively, in the nonrecurrent group. Recurrent P aeruginosa pneumonia in the ICU is associated with increased morbidity and mortality and does not appear to be related to the adequacy of antibiotic treatment. Chronic lung disease appears to predispose patients to recurrent P aeruginosa pneumonia.
A guinea-pig model of experimental Pseudomonas aeruginosa pneumonia was used to determine what factors affect the efficacy of passive immune therapy with a hyperimmune P. aeruginosa globulin (PA-IGIV). Animals treated 2 h after infection with a single iv infusion of PA-IGIV, 500 mg kg-1, demonstrated 33% survival. Lower dosages were less effective and there were no survivors among albumin-treated controls. Treatment with PA-IGIV was effective if given 2 or 8 h after infection but not if delayed until 24 h after infection. Animals rendered neutropenic with cyclophosphamide did not survive if treated with PA-IGIV alone. However, when PA-IGIV was added to tobramycin treatment, a significant increase in survival occurred (86%) as compared with that observed with tobramycin alone (43%) (P less than 0.05). We conclude that PA-IGIV may offer a useful therapeutic option in management of P. aeruginosa pneumonia.
A guinea pig model of experimental Pseudomonas aeruginosa pneumonia was used to evaluate factors affecting the efficacy of passive immune therapy with Psomaglobin N, a hyperimmune P. aeruginosa globulin. Animals treated 2 h after infection with a single intravenous infusion of Psomaglobin N, 500 mg/kg, demonstrated 33% survival. Lower dosages were less effective and no survivors occurred among albumin-treated controls. Treatment with Psomaglobin N was effective if given 2 h or 8 h after infection but not if delayed until 24 h after infection. Animals rendered neutropenic with cyclophosphamide did not survive if treated with Psomaglobin N alone. However, when Psomaglobin N was added to tobramycin treatment, a significant increase in survival occurred (86%) as compared to that observed with tobramycin alone (43%) (p less than 0.05). We conclude that Psomaglobin N may offer a useful therapeutic option in management of P. aeruginosa pneumonia.
The prevalence of protein‐calorie malnutrition (PCM) and micronutrient deficiency (MND) at the time of admission and discharge from hospital was evaluated in 91 patients consecutively admitted to the Surgery Clinic of the University Hospital of Rome.
Anthropometric parameters and circulating levels of vitamins (A, E, C, B1, and B2) and visceral proteins [retinol‐binding protein (RBP, prealbumin (PA), and transferrin] were measured. Twenty‐one patients (23%) had moderate to severe PCM, and 70 patients (77%) had normal nutritional status (NNS) at admission. Two patients with PCM died in the hospital. At discharge, the prevalence of PCM was unchanged in the remaining 19 patents. Single or multiple MND was observed initially in 71% of patients with PCM and in 36% with apparently normal nutritional status. Despite vitamin supplementation, MND was present at the time of discharge in 73% of patients with PCM and 44% with NNS.
Nutritional status at the time of admission was assessed in hospitals in six different Italian cities. The criterion for admission to the study was the diagnosis of chronic (>1 yr duration) illness (excluding cancer and multiple organ disorders). Two hundred eighty‐four patients (145 males, 139 females), ages 25–88 yr, were selected. The findings indicated a high prevalence of MND (64%). Also, in disorders that usually do not have significant alterations of digestion or absorption, such as uncomplicated cardiorespiratory disease, the prevalence of MND was high (9–38%). The prevalence of MND was not related to body mass index (BMI). PCM was more common among patients with chronic gastrointestinal disease. There was a high level of obesity among cardiac patients (BMI>24–25), even though one‐third of them had MND. The prevalence of MND was not related to anthropometric indicators of PCM. (Journal of Parenteral and Enteral Nutrition 11:122S‐125S, 1987)
Pseudomonas aeruginosa has emerged as an important pathogen during the past two decades. It causes between 10% and 20% of infections in most hospitals.
Pseudomonas infection is especially prevalent among patients with burn wounds, cystic fibrosis, acute leukemia, organ transplants,
and intravenous-drug addiction. P. aeruginosa is a common nosocomial contaminant, and epidemics have been traced to many items in the hospital environment. Patients who
are hospitalized for extended periods are frequently colonized by this organism and are at increased risk of developing infection.
The most serious infections include malignant external otitis, endophthalmitis, endocarditis, meningitis, pneumonia, and septicemia.
The likelihood of recovery from pseudomonas infection is related to the severity of the patient's underlying disease process.
The introduction of the antipseudomonal aminoglycosides and penicillins has improved substantially the prognosis of these
infections. Ticarcillin and carbenicillin have been especially beneficial in neutropenic patients; however, prompt institution
of therapy is mandatory for optimal benefit. Many new drugs with antipseudomonal activity, including penicillins, cephalosporins,
and other β-lactams, have been introduced in recent years and offer the potential for new approaches to therapy for these
infections.
With increasing age, chronic underlying disease, and debility, the oropharyngeal flora are colonized with aerobic gram-negative bacilli. In this debilitated population, gram-negative bacillary pneumonias (GNBP) are increasingly common. GNBP account for two of every three pneumonia deaths today. As a group, the mortality of GNBP is about 50%. Although the original epidemiologic surveys were done 15 years ago, there is little evidence for an improving case fatality rate despite the appearance of aminoglycoside antibiotics, carbenicillin, and cephalosporins. In susceptible patients, GNBP pneumonias occur both in the community and as nosocomial infections. Recognition of the dangers of contaminated reservoir nebulizers or other similar devices used in inhalation therapy has led to epidemiologic measures within hospitals that have markedly decreased the incidence of this nosocomial GNBP. The role of Gram stain and culture of expectorated sputum and similar examinations of specimens obtained by transtracheal aspiration, fiberoptic bronchoscopy, and lung biopsy in the diagnosis of GNBP are discussed in this review (see Criteria for Diagnosis). In the presence of pulmonary emphysema, congestive heart failure, mixed gram-negative bacillary infections, or the use of immunosuppressive drugs, typical characteristics of individual GNBP may not be apparent. Typical features of Pseudomonas aeruginosa, Escherichia coli, Enterobacter, Proteus, Hemophilus, and anaerobic pulmonary infections are described. Early recognition and institution of appropriate antibacterial agents are emphasized, particularly in GNBP caused by Pseudomonas aeruginosa, Escherichia coli, or Friedländer's bacillus, where the mortality approaches 70%. The mortality of GNBP, including Enterobacter, Proteus, Hemophilus, and anaerobic GNBP, is about 20%. The latter figure is the same as the mortality of pneumococcal pneumonia in similar patients.
The following case report demonstrates the occasional necessity for staged thoracic surgical intervention in the management of a clinical condition commonly associated with high mortality: overwhelming pseudomonas pulmonary infection and septic shock. Intervention included the use of emergency wide-open drainage of gangrene of the lung and empyema, followed by sequential, interval lobectomy.
Mutants of Pseudomonas aeruginosa PAO1 that were deficient in the ability to produce proteases that degrade casein were detected among the survivors of chemical mutagenesis. One such mutant (PDO31) showed reduced production of elastolytic activity, beta-hemolytic activity, and pyocyanin. A 4.3-kb EcoRI fragment from a gene bank of PAO1 that complemented defects in PDO31 was found. Transposon mutagenesis and deletion derivatives of the clone were used in conjunction with complementation tests to determine the physical location of the gene of interest. Nucleotide sequence analysis revealed an open reading frame (rhlR) encoding a putative 27.6-kDa protein (RhlR) with homology to autoinducer-responsive regulators of quorum sensing systems such as LuxR of Vibrio fischeri and LasR of P. aeruginosa. Further sequence analysis downstream of rhlR revealed an independently transcribed gene (rhlI) that encodes a putative 22.2-kDa protein with homology to members of the family of autoinducer synthetases, such as LuxI of V. fischeri and LasI of P. aeruginosa. The rhlRI sequences were also recently reported by others (U.A. Ochsner and J. Reiser, Proc. Natl. Acad. Sci. USA 92: 6424-6428, 1995) as an autoinducer-mediated regulation mechanism for rhamnolipid biosurfactant synthesis in P. aeruginosa PG201. Mutants with defects in rhlR or rhlI were constructed in PAO1 by gene replacement, using clones modified by Tn501 insertion. Compared with the wild type, the rhlR and rhlI mutants both showed defects in the production of elastase, LasA protease, rhamnolipid, and pyocyanin. Transcription from the gene for elastase, as measured with a lasB-cat fusion, demonstrated that production of elastase was subject to cell density-dependent gene activation in PAO1. However, transcription of lasB-cat in the rhlI mutant, which had lost the presumptive autoinducer synthetase (predicted to activate RhlR), showed low basal activity and had lost all cell density-dependent transcription of lasB. Thus, RhlR-RhlI represent the second autoinducer-responsive regulatory mechanism found in P. aeruginosa that controls expression of multiple virulence factor exoproducts, including elastase.
A murine monoclonal antibody (MAb) specific for the Pseudomonas aeruginosa immunotype 1 (It-1) lipopolysaccharide (LPS) O-side chain was evaluated in terms of its in vitro bactericidal opsonophagocytic activity and in vivo bacterial killing in a mouse thigh infection model. An immunoglobulin (Ig) G2a MAb Ld3-2F2, specific for It-1 LPS, mediated in vitro complement-dependent opsonophagocytic killing at a concentration of 10 microg/ml. MAb-mediated, complement-dependent killing also occurred in the absence of neutrophils at serum concentrations in excess of 20%. A remarkable synergy was observed in opsonophagocytic assays between MAb Ld3-2F2 (0.5 microg/ml) and ceftazidime (1/4 MIC). The administration of MAb Ld3-2F2 at a level of 1 microg resulted in a significant decrease in the number of bacteria in the thigh muscles of normal mice, while 100 microg of the same MAb was required for one log of reduction in the number of bacteria at the same site in neutropenic mice. The combined therapy with MAb Ld3-2F2 and ceftazidime provided a significant reduction in the density of bacteria in the thigh muscle at 9 hr post-infection in normal and neutropenic mice as compared with those after treatment alone or with no treatment (P< 0.01). These favorable in vitro and in vivo interactions of an LPS-specific IgG MAb and ceftazidime strongly support their potential for use in therapy, combined with an LPS-reactive MAb and parenteral antipseudomonas beta-lactam antibiotics in the therapy of systemic Pseudomonas infections in normal and neutropenic hosts.
This article reviews the difficulties in diagnosing and appropriately treating nosocomial pneumonias. Many disorders present with pulmonary infiltrates, fever, and leukocytosis that mimic hospital-acquired pneumonias. Aerobic gram-negative bacilli that reach the lungs by way of aspiration or bacteremia cause Nosocomial pneumonias. Staphylococcus aureus and anaerobes are not important pathogens in nosocomial pneumonia. Culture of respiratory secretions, regardless of technique, reflects the microbiology of proximal and distal airways, which is not proof of the isolates' pathogenicity in lung tissue. Culture of nonpulmonary pathogens or multiple pathogens from respiratory secretions is proof of specimen contamination. Respiratory secretion cultures do not differentiate colonization from infection and should not be the basis of antibiotic selection. Since respiratory secretion cultures are usually misleading, empiric monotherapy should be based on the most likely infectious pathogens, particularly Pseudomonas aeruginosa. Antibiotics selected for empiric monotherapy, or combination therapy, should possess a high degree of anti-Pseudomonas aeruginosa activity, have little or no resistance to potential, a good safety profile, and should be relatively inexpensive.
The purpose of this study was to evaluate CT findings in nosocomial Pseudomonas aeruginosa Pneumonia (PAP) and to compare features of PAP in patients with isolated P. aeruginosa cultures and those with coexistent infections. A retrospective database search revealed 28 patients with nosocomial PAP (12 men, 16 women; mean age, 57 years) in which thoracic CT had been performed within a mean of 1.7 days from the time of respiratory culture. Two chest radiologists blinded to culture data performed a consensus reading noting distribution and pattern of consolidation, ground-glass opacity, nodules, peribronchial infiltration, necrosis, effusions, and pleural enhancement. Coexistent respiratory cultures were recorded. Consolidation was present in all patients, involving multiple lobes in 23 (82%) and demonstrating upper zonal involvement in 23 (82%). Nodular features were present in 14 (50%), including tree-in-bud patterns with centrilobular distributions in 9 (64%) and larger, randomly distributed nodules in 5 (36%). Five of five patients with consolidations limited to the lower lung zones had associated upper lung nodules. Ground-glass opacity was seen in nine (31%) and peribronchial infiltration in 16 (57%). Necrosis was present in eight (29%). Thirteen (46%) bilateral and five (18%) unilateral pleural effusions were present with enhancement occurring in two (1%). Coexistent positive respiratory cultures were identified in 13 patients. The distribution of consolidation, frequency and distribution of nodules, and frequency of necrosis did not differ significantly between patients with and without other positive cultures. With CT, PAP most commonly presents with multifocal airspace consolidation. Nodular features were identified in half, with one-third demonstrating tree-in-bud opacities. Unsuspected necrosis occurred in one-third of cases. CT findings in patients with and without other respiratory isolates did not differ in the distribution and frequency of consolidations, nodularity, or necrosis.
Gram-negative bacilli (GNB) are a common cause of severe hospital-acquired pneumonia. Due to changes in the health care environment and selective antimicrobial pressure, these bacteria also are becoming a more common cause of pneumonia in venues outside of the traditional hospital setting and are increasingly resistant to antimicrobial agents. Risk factors for acquisition of GNB allow the clinician to efficiently identify patients who are likely to have pneumonia due to these pathogens. Available diagnostic techniques have a limited capacity to accurately detect GNB pulmonary infection. Yet, a pathogen specific diagnosis and knowledge of local resistance patterns are quintessential elements in formulating an effective treatment plan. This article reviews the epidemiologic characteristics, pathogenesis, and current management issues of GNB pneumonia.
Pneumonia is a frequent cause of mortality and morbidity in the elderly. This article discusses pneumonia in the elderly based on causative organisms and sites where the pneumonia was acquired. Community-acquired pneumonia, nursing home-acquired pneumonia and nosocomial pneumonia in the elderly are reviewed from a diagnostic and therapeutic perspective. Optimal antimicrobial therapy is based on knowledge of the pulmonary pathogens associated with community-acquired, nursing home-acquired and nosocomial pneumonias. Antibiotic dosing should take into account the functional action of the liver and kidneys in individuals of advanced age.
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