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Combination therapy for treatment of Pseudomonas aeruginosa bloodstream infections.

ABSTRACT: OBJECTIVES:Management of bloodstream infections ("BSIs") caused by Pseudomonas aeruginosa remains controversial as data supporting the use of definite combination treatment for severe P. aeruginosa infections remain conflicting. We aimed to determine differences in mortality between patients treated with definite combination therapy and monotherapy in a large 11-year cohort. METHODS:All consecutive patients with P. aeruginosa BSI hospitalized at the University Hospital Basel, Switzerland, a tertiary academic care center, from January 2003 to December 2013 were included. Pertinent clinical data was assessed. Patients with and without definite combination therapy were compared and hazard ratios for death were calculated. RESULTS:During the study period, 187 patients with P. aeruginosa BSI were identified. Definite combination therapy was administered in 42.8% (80/187) of all patients, of which 76% (61/80) received a combination of a betalactam with an aminoglycoside and 24% (19/80) received a combination of a betalactam with a quinolone. The remaining 57.2% (107/187) were treated with betalactam monotherapy. Median treatment duration was 15 days (interquartile range 12-20 days). Mortality was lower in patients receiving definite combination therapy in univariable and multivariable cox regression analyses (HR 0.26, 95% CI 0.11-0.60, p = 0.002 and HR 0.30, 95% CI 0.13-0.71, p = 0.006, respectively), the latter adjusting for age, neutropenia at diagnosis, PITT bacteremia score, and inadequate empirical treatment. CONCLUSIONS:Combination therapy (i.e. betalactam-aminoglycoside or betalactam-quinolone combinations) may improve survival of P. aeruginosa BSI, independent of potential confounders such as age, neutropenia, PITT bacteremia score, and inadequate empirical treatment.

SUBMITTER: Tschudin-Sutter S

PROVIDER: S-EPMC6147480 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Combination therapy for treatment of Pseudomonas aeruginosa bloodstream infections.

Tschudin-Sutter Sarah S Fosse Nicole N Frei Reno R Widmer Andreas F AF

PloS one 20180920 9

<h4>Objectives</h4>Management of bloodstream infections ("BSIs") caused by Pseudomonas aeruginosa remains controversial as data supporting the use of definite combination treatment for severe P. aeruginosa infections remain conflicting. We aimed to determine differences in mortality between patients treated with definite combination therapy and monotherapy in a large 11-year cohort.<h4>Methods</h4>All consecutive patients with P. aeruginosa BSI hospitalized at the University Hospital Basel, Swit ...[more]

PMID: 30235247

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Project description:Pseudomonas aeruginosa frequently becomes resistant to aminoglycosides by the acquisition of aminoglycoside modifying enzyme (AME) genes and the occurrence of mutations in the mexZ, fusA1, parRS, and armZ genes. We examined resistance to aminoglycosides in a collection of 227 P. aeruginosa bloodstream isolates collected over 2 decades from a single United States academic medical institution. Resistance rates of tobramycin and amikacin were relatively stable over this time, while the resistance rates of gentamicin were somewhat more variable. For comparison, we examined resistance rates to piperacillin-tazobactam, cefepime, meropenem, ciprofloxacin, and colistin. Resistance rates to the first four antibiotics were also stable, although uniformly higher for ciprofloxacin. Colistin resistance rates were initially quite low, rose substantially, and then began to decrease at the end of the study. Clinically relevant AME genes were identified in 14% of isolates, and mutations predicted to cause resistance were relatively common in the mexZ and armZ genes. In a regression analysis, resistance to gentamicin was associated with the presence of at least one gentamicin-active AME gene and significant mutations in mexZ, parS, and fusA1. Resistance to tobramycin was associated with the presence of at least one tobramycin-active AME gene. An extensively drug-resistant strain, PS1871, was examined further and found to contain five AME genes, most of which were within clusters of antibiotic resistance genes embedded in transposable elements. These findings demonstrate the relative contributions of aminoglycoside resistance determinants to P. aeruginosa susceptibilities at a United States medical center. IMPORTANCE Pseudomonas aeruginosa is frequently resistant to multiple antibiotics, including aminoglycosides. The rates of resistance to aminoglycosides in bloodstream isolates collected over 2 decades at a United States hospital remained constant, suggesting that antibiotic stewardship programs may be effective in countering an increase in resistance. Mutations in the mexZ, fusA1, parR, pasS, and armZ genes were more common than acquisition of genes encoding aminoglycoside modifying enzymes. The whole-genome sequence of an extensively drug resistant isolate indicates that resistance mechanisms can accumulate in a single strain. Together, these results suggest that aminoglycoside resistance in P. aeruginosa remains problematic and confirm known resistance mechanisms that can be targeted for the development of novel therapeutics.

Project description:Bacterial co-infections increase the severity of respiratory viral infections and are frequent causes of mortality in COVID-19 infected subjects. During the COVID-19 period, especially at the beginning of the pandemic, an inappropriate use of broad-spectrum antibiotic treatments has been frequently described, mainly due to prolonged hospitalization, especially in intensive care unit departments, and the use of immune-suppressive treatments as steroids. This misuse has finally led to the occurrence of infections by multi-drug resistant (MDR) bacteria in hospitalized COVID-19 patients. Although different reports assessed the prevalence of Gram-negative infections in COVID-19 infected patients, scarce data are currently available on bloodstream infections caused by Pseudomonas aeruginosa in hospitalized COVID-19 patients. The aim of our systematic review is to describe data on this specific population and to discuss the possible implications that these co-infections could have in the management of COVID-19 pandemics in the future. We systematically analysed the current literature to find all the relevant articles that describe the occurrence of P. aeruginosa bloodstream infections in COVID-19 patients. We found 40 papers that described in detail P. aeruginosa HAIs-BSI in COVID-19 patients, including 756,067 patients overall. The occurrence of severe infections due to MDR bacteria had a significant impact in the management of hospitalized patients with COVID-19 infections, leading to a prolonged time of hospitalization and to a consequent increase in mortality. In the near future, the increased burden of MDR bacteria due to the COVID-19 pandemic might partially be reduced by maintaining the preventive measures of infection control implemented during the acute phase of the COVID-19 pandemic. Finally, we discuss how the COVID-19 pandemic changed the role of antimicrobial stewardship in healthcare settings, according to the isolation of MDR bacteria and how to restore on a large scale the optimization of antibiotic strategies in COVID-19 patients.

Project description:Pseudomonas aeruginosa is a Gram-negative rod and an etiological factor of opportunistic infections. The infections of this etiology appear mostly among hospitalized patients and are relatively hard to treat due to widespread antimicrobial resistance. Many virulence factors are involved in the pathogenesis of P. aeruginosa infection, the coexistence of which have a significant impact on the course of an infection with a particular localization. The aim of this study was to assess the antimicrobial susceptibility profiles and the frequency of genes encoding selected virulence factors in clinical P. aeruginosa strains isolated from bloodstream infections (BSIs). The following genes encoding virulence factors of enzymatic activity were assessed: lasB, plC H, plC N, nan1, nan2, aprA and phzM. The frequency of the genes encoding the type III secretion system effector proteins (exoU and exoS) and the genes encoding pilin structural subunits (pilA and pilB) were also investigated. The occurrence of virulence-factor genes was assessed using polymerase chain reactions, each in a separate reaction. Seventy-one P. aeruginosa strains, isolated from blood samples of patients with confirmed bacteremia hospitalized at the University Hospital No. 1 of Dr. Antoni Jurasz in Bydgoszcz, Poland, were included in the study. All the investigated strains were susceptible to colistin, while the majority of the strains presented resistance to ticarcillin/clavulanate (71.8%), piperacillin (60.6 %), imipenem (57.7%) and piperacillin/tazobactam (52.1%). The presence of the lasB and plC H genes was noted in all the tested strains, while the plC N, nan2, aprA, phzM and nan1 genes were identified in 68 (95.8%), 66 (93.0%), 63 (88.7%), 55 (77.5%) and 34 (47.9%) isolates, respectively. In 44 (62.0%) and 41 (57.7%) strains, the presence of the exoU and exoS genes was confirmed, while the pilA and pilB genes were noted only in 14 (19.7%) and 3 (4.2%) isolates, respectively. This may be due to the diverse roles of these proteins in the development and maintenance of BSIs. Statistically significant correlations were observed between particular gene pairs' coexistence (e.g., alkaline protease and neuraminidase 2). Altogether, twenty-seven distinctive genotypes were observed among the studied strains, indicating the vast variety of genetic compositions of P. aeruginosa strains causing BSIs.

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Combination therapy for treatment of Pseudomonas aeruginosa bloodstream infections.

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Combination therapy for treatment of Pseudomonas aeruginosa bloodstream infections.

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