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(A) Incidence rate of first GNR bacteremia event, by transplantation year, 2003 to 2012. (B) Incidence rate of all GNR bacteremia events, by transplantation year, 2003 to 2012.
Source publication
There are concerns that emerging resistance to fluoroquinolones (FQ) may be leading to increasing rates of gram-negative rod (GNR) bacteremia in hematopoietic cell transplant (HCT) recipients. We set out to describe time trends in the incidence rates (IR) of GNR bacteremia and FQ-resistant GNR bacteremia in HCT recipients during an era of levofloxa...
Citations
... While fluoroquinolone prophylaxis has been shown to be effective in reducing gram-negative infections in neutropenic patients, its benefits on mortality have not been consistently demonstrated [10,[15][16][17][18] Furthermore, fluoroquinolone prophylaxis has been linked to a higher risk of fluoroquinolone-resistant gram-negative bacteria and Staphylococcus species, as well as the development of Clostridium difficileassociated diarrhea [19][20][21] In contrast, another study found that fluoroquinolone prophylaxis reduced the incidence of bacteremia after autologous hematopoietic cell transplantation without increasing the occurrence of C. difficile infections [22]. Furthermore, fluoroquinolone-resistant bacteremia has been linked to a higher mortality rate than fluoroquinolone-sensitive bacteremia [23]. Comparative studies in the literature, which have examined groups using different medications or compared medication usage with non-usage, found that levofloxacin prophylaxis can decrease the frequency of central line-associated infections but may increase the occurrence of infections caused by resistant strains [24]. ...
Background
Despite preventive measures and varying antibiotic recommendations, bacterial infections continue to pose a significant threat to individuals undergoing hematopoietic stem cell transplantation (HSCT). Levofloxacin prophylaxis is commonly used, but the optimal timing for initiation is debated. This study aims to assess infection outcomes based on timing of levofloxacin prophylaxis (initiation at the first day of conditioning vs. after infusion of stem cells) in autologous and allogeneic HSCT patients.
Methods
We compared infectious episodes, responsible pathogens, and clinical outcomes based on the implementation of levofloxacin prophylaxis in patients receiving autologous or allogeneic HSCT procedures. This retrospective single-center study involved a review of the medical records of autologous and allogeneic HSCT patients treated at our adult stem cell transplantation unit between 2018 and 2020. The study included 23 patients who underwent autologous HSCT and 12 patients who underwent allogeneic HSCT. We compared the demographic data, febrile neutropenia, proven bacterial infections, and 30-day survival among the autologous and allogeneic transplant groups, including those who received oral levofloxacin 500 mg/day prophylaxis.
Results
Positive blood cultures (26.1% vs. 75%; p = 0.011), mean neutrophil engraftment (10.6±1.2 vs. 14.8±1.3; p<0.001), and mean platelet engraftment (11.2±1.1 vs. 15.4±3.2; p = 0.004) were all lower in autologous transplant patients versus their allogeneic counterparts. When each type of HSCT was evaluated within the same type, there were no observed differences in infection frequency, infection type, or 30-day mortality between the patient groups with different levofloxacin initiation times.
Conclusion
Healthcare professionals should choose the most appropriate timing for initiating levofloxacin prophylaxis based on individual patient factors and clinical circumstances while considering the cost-effectiveness implications. Further research with a larger sample size and prospective design is needed to support our findings.
... A systematic review 3 and meta-analysis 4 , which included studies up to a decade ago, showed that FQ prophylaxis decreased bacteremia in allogeneic HCT (allo-HCT) recipients. Subsequently, several recent studies from developed regions with a lower prevalence of FQ resistance have confirmed this [5][6][7] . However, there is a weak recommendation against routine FQ prophylaxis in pediatric HCT recipients 8,9 . ...
... Most studies from high-income countries with a low prevalence of FQ resistance have found a beneficial effect of FQ prophylaxis on reducing the incidence of GNB bacteremia in the adult allo-HCT setting [5][6][7] . There is always weak evidence of FQ prophylaxis in the pediatric allo-HCT settings 8 . ...
Introduction:
The role of fluoroquinolone (FQ) prophylaxis in preventing gram-negative bacilli (GNB) bacteremia, graft-versus-host disease (GVHD), and overall survival (OS) after allogeneic hematopoietic cell transplantation (allo-HCT) is debatable and may differ in settings with low and high prevalences of FQ resistance. In this study, we aimed to answer this question in regions with high FQ resistance.
Methods:
This single-center retrospective study included all consecutive allo-HCT recipients aged ≥12 years from 2012 to 2021. Allo-HCT recipients until 2016 were administered FQ prophylaxis (levofloxacin). After 2016, the institutional protocol was modified to no antibiotic prophylaxis. Data were retrieved from patient records for disease and transplant characteristics, the incidence of GNB bacteremia, duration of parenteral antibiotics, hospitalization duration, acute GVHD, and OS.
Results:
A total of 135 allo-HCT recipients (43 in the FQ-prophylaxis cohort and 92 in the no-antibiotic prophylaxis cohort) were analyzed in this study. The two cohorts were matched for age (median, 26 vs. 24.5 years; p = 0.8). The no-antibiotic prophylaxis cohort had a higher proportion of malignant diagnoses (80% vs. 58%, p = 0.01), haploidentical transplants (46% vs. 14%, p = 0.004), and posttransplant cyclophosphamide exposure (46% vs. 14%, p = 0.003) than did the FQ cohort. Despite this, the incidence of GNB bacteremia was not significantly different between the two cohorts (37% vs. 34%, p = 0.6). There were no differences in parenteral antibiotic use or hospitalization duration, as well as the incidence of acute GVHD (53% vs. 53%, p = 0.3). The 1-year OS was similar between the two cohorts (66% vs. 67%, p = 0.6).
Conclusion:
This study shows that FQ prophylaxis did not affect the incidence of GNB bacteremia, parenteral antibiotic use, hospitalization duration, acute GVHD, and OS post-allo-HCT.
... Resistance to fluoroquinolones have been reported in 50% of gram-negative isolates in patients receiving fluoroquinolone prophylaxis. In a study by Miles-Jay A et al, the rates of fluoroquinolone resistance has been found to be static over 10 years of prophylaxis [35]. ...
... Levofloxacin use is associated with acquisition of quinolone-resistant infections. A single-center study reported by Miles-Jay et al. demonstrated an increase in the rate of fluoroquinolone-resistant gram-negative infections among allogeneic HSCT recipients in the era of levofloxacin prophylaxis [44]. In 2017, Averbuch et al. reported 50% quinolone resistance and 19% carbapenem resistance in centers using fluoroquinolone prophylaxis across 25 countries in Europe, Australia, and Asia [45]. ...
... Though contrary to other studies among pediatric populations where the incidence of resistance was low among children and not significantly different between the levofloxacin prophylaxis and control groups, follow-up for infections was longer, perhaps highlighting the longterm consequences of this practice [35,45]. The emergence of resistance is concerning as infections with resistant pathogens are associated with higher mortality compared to those from more susceptible pathogens (21 vs 10%), likely related to delay in initiation of appropriate antibiotics [44]. ...
Purpose of review
Bacterial sepsis is a leading cause of morbidity and mortality among pediatric cancer patients receiving intensive chemotherapy. While there are treatment guidelines for empiric antimicrobial therapy for fever with neutropenia, the role of prophylactic antibacterial agents has been widely debated and is less well-defined.
Recent findings
Demonstrable benefits of fluoroquinolone prophylaxis (specifically levofloxacin) include prevention of bacteremia and potentially fevers during neutropenia, though with limited if any impact on mortality. However, the risks of using antibacterial prophylaxis include antimicrobial over-utilization, antimicrobial resistance, Clostridioides difficile colitis, and stool dysbiosis with associated risk of graft versus host disease and mortality.
Summary
This review article outlines the current literature and provides guidance for decisions about levofloxacin prophylaxis in the pediatric oncology population.
... We observed a low overall prevalence of GNRB and, in agreement with previous studies, a significant decline in the incidence of GNRB. 24,25 We had assumed that outpatient antibiotic treatment time would increase over time given the increasing proportion of F I G U R E 1 Flowchart of adult allogeneic hematopoietic cell transplant recipient inclusion Legend: Flowchart of hematopoietic cell transplant (HCT) recipient study population. Gram-negative rod bacteremia (GNRB) was identified using blood culture confirmation and we limited the analysis to first GNRB during patient follow-up (first 100 days posttransplant). ...
Introduction:
The increasing proportion of outpatient allogeneic hematopoietic cell transplants (HCTs) coupled with increased access of once-daily broad-spectrum antibiotics and evidence that outpatient antibiotic treatment may be safer and less costly than inpatient treatment, suggest that allogeneic HCT recipients with Gram-negative rod bacteremia (GNRBs) are increasingly being treated in ambulatory care settings.
Methods:
Using data from the first GNRB event that occurred within the first 100 days posttransplantation among allogeneic HCT recipients transplanted at a single center between 2007 and 2016, we estimated the temporal trends in GNRB incidence and treatment management of GNRBs and identified if patient or infection characteristics impacted observed trends.
Results:
A total of 11% (238/2165) of the observed allogeneic HCT recipients experienced ≥1 GNRB with available resistance data and contributed antibiotic treatment time. Patients, on average, received 55.1% of their antibiotic treatment in an outpatient setting and we observed a significant decline in the proportion of treatment time spent outpatient (crude: -3.3% [95% confidence interval: -5.0, -1.6%]). We observed similar declines in the proportion of treatment time spent outpatient among patients with similar GNRB and pretransplant complexity factors but not among patients with similar posttransplant complications (p value: .165).
Conclusion:
These results suggest that, despite increased availability of outpatient suitable treatment options, allogeneic HCT recipients with GNRBs received less treatment in outpatient settings. However, among patients with similar posttransplant complications, the lack of significant decline suggests that treatment location decisions remained consistent for patients with similar posttransplant complications. These findings suggest the need for additional interventions targeting outpatient antibiotic treatment among allogeneic HCT recipients with GNRBs.
... Levofloxacin is preferred over ciprofloxacin because of its better coverage against S. viridans. The use of vancomycin is associated with the appearance of vancomycin-intermediate S. aureus and vancomycin-resistant Enterococcus [13] and the use of fluoroquinolones is associated with the appearance of BGN infections resistant to them [14]. ...
... E coli isolation has increased significantly in recent years in oncology settings. 15 ESBL E coli infections have been associated with higher mortality in cancer patients, particularly in patients with hematologic malignancies. [16][17][18][19][20] The resistance to methicillin in S aureus was 25.4%, lower than that reported in other series in the United States (45.6%). ...
Introduction:
Central venous catheters (CVCs) are essential for treating cancer patients, but infection is a risk associated with their use, particularly by multidrug-resistant (MDR) bacteria. The aim of this study was to describe the microbiology of catheter-related bloodstream infections (CRBSIs) in cancer patients and to compare the prevalence of MDR ESKAPE microorganisms (Enterococcus faecium, Staphylococcus spp, Klebsiella spp, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp) plus Escherichia coli (E2SKAPE).
Methods:
Based on data from 2013 to 2015 from a prospective survey of CRBSIs by the intravenous therapy team, we describe the microbiology and compare the prevalence of MDR E2SKAPE strains between hospitalized patients and outpatients.
Results:
A total of 469 episodes of CRBSI were diagnosed: 261 (62%) were in women; 87 (18.6%) occurred in hospitalized patients, and 382 (81.4%) in ambulatory patients; 27.5% of patients had a hematologic malignancy and 72.5% a solid tumor. The median time between CVC insertion and CRBSI was 116 days (interquartile range [IQR], 48-207). The most common bacteria isolated were Staphylococcus epidermidis (18.1%), S aureus (10.9%), E coli (7.7%), and Klebsiella spp (8.6%). E2SKAPE accounted for 35.6%. Methicillin-resistant Staphylococcus aureus (MRSA) (odds ratio [OR], 16.4; 95% confidence interval [CI], 1.6-114; P = .01), extended-spectrum beta-lactamase (ESBL) Klebsiella spp (OR, 26; 95% CI, 2-286; P = .007), and ESBL E coli (OR, 26; 95% CI, 2-286; P = .007) were significantly more frequently isolated from hospitalized vs ambulatory patients.
Conclusions:
MRSA, ESBL E. coli and ESBL Klebsiella spp were significantly more frequently isolated from hospitalized patients with CRBSI.
... Las bacteriemias causadas por bacterias Gram negativas (BGN) resistentes a los antibióticos han sido asociadas a tasas crecientes de fallo en el tratamiento, mortalidad y costos hospitalarios (33)(34)(35)(36)(37)(38). ...
La leucemia aguda ha sido reconocida como una enfermedad compleja y rápidamente fatal desde su primera descripción hace 150 años. Librada a su historia natural, la leucemia mieloide aguda lleva a la muerte en pocos meses. Las infecciones son la principal causa de muerte, siendo la bacteriemia y la neumonía las más frecuentes.Los avances ocurridos en los últimos 50 años, como el advenimiento de quimioterapias efectivas, la mejor comprensión de la patogénesis de las complicaciones infecciosas en el paciente neutropénico, la disponibilidad de agentes anti infecciosos de amplio espectro y la mejoría en los cuidados de soporte contribuyeron a mejorar esta situación.En relación a otras enfermedades oncohematológicas, la leucemia mieloide aguda registra la mayor incidencia de eventos febriles, siendo el período de mayor riesgo el de la inducción a la remisión.La fiebre de origen desconocido, la multirresistencia bacteriana y las infecciones fúngicas invasivas constituyen un desafío para el equipo de trabajo.El uso de profilaxis antibacteriana y antifúngica no reemplaza a las medidas de prevención de carácter institucional.
... b Gram-negative Bacteria. [48,91,[104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121] $14 billion to over $3 trillion (2013 USD) in loss to global GDP by 2050 [15,55]. Whilst the studies which utilised multistate modelling techniques (including decision tree analysis) or stepwise calculations, estimated national costs for a specific resistance type to range from over $20,000 per MRSA bloodstream infection case to over $7 billion per year attributable to community acquired MRSA in the United States (Table 4) [56,57]. ...
Background
Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base.
Methods
MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD.
Results
Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from $21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively.
Conclusions
This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review.
Trial registration
This systematic review is registered with PROSPERO (PROSPERO CRD42016037510).
Electronic supplementary material
The online version of this article (10.1186/s13756-018-0336-y) contains supplementary material, which is available to authorized users.
... 10,11 Moreover, routine quinolone prophylaxis in such settings has been associated with increasing resistance to this antimicrobial group amongst Gramnegative bacteria, as well as increased rates of methicillin-resistant staphylococci and vancomycin-resistant enterococci. [12][13][14][15][16][17][18][19] Several centers have therefore abandoned routine antibacterial prophylaxis in the context of HSCT or have limited its use to high-risk patients (i.e., those with expected neutropenia for >7 days). 5,20,21 Centers that continue to employ routine antibacterial prophylaxis should monitor their bacterial resistance rates and modify their practices accordingly. ...
Bacterial infections remain a common complication of hematopoietic stem cell transplantation (HSCT), especially in the pre-engraftment phase. The risk of bacterial infections is mainly related to neutropenia, mucositis, and the presence of vascular lines. Most parts of the world have witnessed a shift in epidemiology towards Gram-negative bacteria; a large proportion of which are resistant to fluoroquinolones, extended-spectrum beta-lactams, carbapenems, and in some units even colistin. Meticulous infection control practices are essential for prevention of bacterial infections in HSCT. The role of routine prophylactic antibiotics is limited in settings with high rates of bacterial resistance. If used, prophylactic antibiotics should be limited to high-risk patients, and the agents are selected based on local resistance profiles. Neutropenic fever is a medical emergency in most HSCT recipients. Prompt clinical evaluation is paramount, along with the intravenous administration of appropriate empiric antimicrobials, typically an antipseudomonal beta-lactam agent. Glycopeptides should only be considered if the patient is hemodynamically unstable or Gram-positive infection is suspected. Additional Gram-negative agents, such as colistin or aminoglycosides, may be added if extensive Gram-negative resistance is expected. To mitigate increasing bacterial resistance, empiric antibiotic regimens should be rationalized or discontinued as soon as possible.
