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Pseudomonas aeruginosa bloodstream infection at a tertiary referral hospital for children

ABSTRACT: Background This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. Methods A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. Results The incidence risk of PABSI was 5.4 (95% CI: 4.34–6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. Conclusions PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.

SUBMITTER: Dame J

PROVIDER: S-EPMC7541237 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:Carbapenem resistance presents severe threat to the treatment of multidrug resistant Pseudomonas aeruginosa infections. The study was undertaken to investigate the role of efflux pumps in conferring meropenem resistance and effect of single dose exposure of meropenem on transcription level of mexA gene in clinical isolates of P. aeruginosa from a tertiary referral hospital of India. Further, in this investigation an effort was made to assess whether different components of MexAB-OprM operon expresses in the same manner and the extent of contributions of those components in meropenem resistance in its natural host (P. aeruginosa) and in a heterologous host (E. coli). Out of 83 meropenem nonsusceptible isolates, 22 isolates were found to possess efflux pump activity phenotypically. Modified hodge test and multiplex PCR confirmed the absence of carbapenemase genes in those isolates. All of them were of multidrug resistant phenotype and were resistant to all the carbepenem drug tested. MexAB-OprM efflux pump was found to be overexpressed in all the study isolates. It could be observed that single dose exposure meropenem could give rise to trivial increase in transcription of mexA gene. Different constructs of MexAB-OprM (mexR-mexA-mexB-OprM; mexA-mexB-OprM; mexA-mexB) could be expressed in both its natural (P. aeruginosa PAO1) and heterologous host (E. coli JM107) but transcription level of mexA gene varied in both the hosts before and after single dose exposure of meropenem. Different components of the operon failed to enhance meropenem resistance in E. coli JM107 and P. aeruginosa PAO1. This study could prove that MexAB-OprM efflux pump can significantly contribute to meropenem resistance in hospital isolates of P. aeruginosa where an acquired resistant mechanism is absent. Thus, equal importance should be given for diagnosis of intrinsic resistance mechanism so as to minimize treatment failure. As meropenem could not enhance mexA transcriptions significantly, there might be a possibility that the increase in expression of efflux pump genes does not mediated by single antibiotic but rather by a combination of antipseudomonal drugs which are used during treatments. Early detection of efflux genes will help in selection of proper therapeutic options.

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:IntroductionInjury accounts for more than 5.8 million deaths globally with an increasing burden in the developing world. In Kenya, trauma is one of the top 10 leading causes of death. However, no formal continuous injury surveillance systems are in place to inform injury prevention, pre-hospital care or emergency department management. The aim of this study was to implement a hospital-based trauma registry to characterize high acuity injuries presenting to a private tertiary, teaching and referral hospital in Kenya.MethodsFrom January to December 2015, data was prospectively collected at a private tertiary, teaching and referral hospital in Nairobi, Kenya. Patients presenting with a traumatic injury for the first time who were admitted to the hospital for at least 48 hours were included in the study. Basic information pertaining to demographics, details of the injury, pre-hospital care and transport, hospital-based management, length of stay and disposition were collected. An injury severity score (ISS) was calculated on each patient and stratified by the mechanism of injury. Descriptive statistics and multivariate logistic regression were used to analyze data and assess risk factors associated with injury severity.ResultsThere were 101 patients included in the study, the majority of whom were 30 to 39 years of age and male (63%). Seventy-one per cent of patients had a preexisting medical condition with hypertension (26%) and diabetes (13%) being the most common. The most common mechanism of injury was fall (46%) followed by road traffic incidents (RTI) (32%). Most injuries took place at home (43%). Most RTI were caused by cars (63%), with the driver being the most frequently injured (38%). The most common mode of arrival to the emergency department was by private car (72%). The median time between the accident and arrival at the emergency department was 1hr 10 minutes. The majority of the patients had injuries to one area (83%) with the extremities/bony pelvis (72%) being the most common. The median Injury Severity Score was 5 (range 1-34) with the majority (90%) classified as minor injuries (ISS<12). The highest severity of injury as determined by ISS was seen in gunshot wounds.ConclusionsInjured patients in Kenya showed concordance with prior studies looking at injury prevalence in the developing world when looking at demographics and place of injury. However, differences were found when looking at the mechanism of injury, with falls surpassing road traffic incidents. A delayed presentation to the hospital was also noted in this patient population. Given the rate of traumatic injuries in Kenya and their contribution to morbidity, mortality and overall healthcare costs, there is a need to implement formal trauma registries in all major hospitals in Kenya to generate more data that can be used to improve injury prevention, the overall trauma system and enhance training and preparedness.

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Pseudomonas aeruginosa bloodstream infection at a tertiary referral hospital for children

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