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Tracking colistin-treated patients to monitor the incidence and outcome of carbapenem-resistant Gram-negative infections.

ABSTRACT: Existing surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown.A retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or died during therapy (termed colistin cases). The primary outcomes were the number of colistin cases per 100,000 admissions per year and change in the hospital mortality rate over time compared with the rate of discharges to home. Secondary outcomes included median overall and intensive care unit lengths of stay.From 2006 to 2012, a total of 5011 unique patients were identified as colistin cases. The number per 100,000 admissions per year increased from 35.56 to 92.98 during the 7-year study (P < .001). The odds of in-hospital death among colistin cases (compared with discharge to home) decreased by a mean of 5.2%/y (P = .04), whereas discharge to an institution (P = .24) or hospice (P = .89) remained steady over time. The median overall and intensive care unit lengths of stay decreased by 7.5 and 6 days, respectively (P < .001). In a 4-hospital chart review, 81.6% of colistin cases were found to have culture-positive CRGNIs. Conversely, 53% of extensively drug-resistant bloodstream CRGNIs at 2 of these hospitals met colistin case criteria.Colistin cases represent a severely ill population with a high probability of having culture-confirmed CRGNIs. Colistin tracking is a novel strategy for monitoring the incidence and mortality of CRGNIs, particularly those caused by extensively drug-resistant bacteria. Although the incidence of colistin cases nearly tripled within 7 years, more of these patients are surviving hospitalization and going home.

SUBMITTER: Kadri SS

PROVIDER: S-EPMC4296128 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Tracking colistin-treated patients to monitor the incidence and outcome of carbapenem-resistant Gram-negative infections.

Kadri Sameer S SS Hohmann Samuel F SF Orav E John EJ Bonne Stephanie L SL Moffa Matthew A MA Timpone Joseph G JG Strich Jeffrey R JR Palmore Tara T Christopher Kenneth B KB Varughese Christy C Hooper David C DC Danner Robert L RL

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20140922 1

<h4>Background</h4>Existing surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown.<h4>Methods</h4>A retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or ...[more]

PMID: 25246597

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Project description:BACKGROUND:Rates of colonization and infection with carbapenem-resistant Gram-negative pathogens are on the rise, particularly in southeastern European countries, and this is increasingly true in Germany as well. The organisms in question include enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli and non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As the carbapenems have been the gold standard to date for the systemic treatment of serious infections with Gram-negative bacteria, carbapenem resistance presents new and difficult challenges in therapeutic decision-making, particularly because of the high frequency of coresistance. METHODS:This review is based on pertinent publications retrieved by a selective search in PubMed and on other applicable literature. RESULTS:Multiresistant Gram-negative (MRGN) pathogens are classified in Germany according to their resistance to four different classes of antibiotics; fluoroquinolones, piperacillin, third-generation cephalosporins, and carbapenems. Quadruple MRGN pathogens are resistant to all four groups, triple MRGN pathogens to three of them. There are a number of therapeutic alternatives to carbapenems that can be applied with the aid of sensitive microbiological and/or molecular genetic testing. The following antibiotics are often the only ones that can be used to treat quadruple MRGN pathogens: colistin, aminoglycosides, tigecycline, fosfomycin, ceftazidime/avibactam, and ceftolozan/tazobactam. Carbapenems, too, may still be an option in certain situations. There is also evidence that combinations of antibiotics against which the pathogen is resistant individually can some- times be a valid treatment option; these include combinations of colistin with one or two carbapenems. CONCLUSION:The treatment of severe infection with carbapenem-resistant pathogens should be individualized and carried out in an interdisciplinary framework, in consideration of antibiotic pharmacokinetics and pharmacodynamics in each case. The treat- ment options are based on evidence from in vitro studies, retrospective studies, and case series, which must be interpreted with caution. Randomized clinical trials are needed to test each of the various combined approaches.

Project description:The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification.This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings.The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.NCT01732250 and 2012-004819-31; Pre-results.

Project description:In recent years, extended ESBL and carbapenemase producing Gram negative bacteria have become widespread in hospitals, community settings and the environment. This has been triggered by the few therapeutic options left when infections with these multi-drug resistant organisms occur. The emergence of resistance to colistin, the last therapeutic option against carbapenem-resistant bacteria, worsened the situation. Recently, animals were regarded as potent antimicrobial reservoir and a possible source of infection to humans. Enteric Gram negative bacteria in animals can be easily transmitted to humans by direct contact or indirectly through the handling and consumption of undercooked/uncooked animal products. In the Mediterranean basin, little is known about the current overall epidemiology of multi-drug resistant bacteria in livestock, companion, and domestic animals. This review describes the current epidemiology of ESBL, carbapenemase producers and colistin resistant bacteria of animal origin in this region of the world. The CTX-M group 1 seems to prevail in animals in this area, followed by SHV-12 and CTX-M group 9. The dissemination of carbapenemase producers and colistin resistance remains low. Isolated multi-drug resistant bacteria were often co-resistant to non-beta-lactam antibiotics, frequently used in veterinary medicine as treatment, growth promoters, prophylaxis and in human medicine for therapeutic purposes. Antibiotics used in veterinary medicine in this area include mainly tetracycline, aminoglycosides, fluoroquinolones, and polymyxins. Indeed, it appears that the emergence of ESBL and carbapenemase producers in animals is not related to the use of beta-lactam antibiotics but is, rather, due to the co-selective pressure applied by the over usage of non-beta-lactams. The level of antibiotic consumption in animals should be, therefore, re-considered in the Mediterranean area especially in North Africa and western Asia where no accurate data are available about the level of antibiotic consumption in animals.

Project description:Purpose:Carbapenems are considered the most efficient antibiotic used in the treatment of nosocomial infections. Carbapenem-resistant Gram-negative rods are becoming a serious hazard in hospitals threatening public health. The aim of the current study was to investigate the prevalence of carbapenem-resistant Gram-negative pathogens incriminated in healthcare-associated infections, along with antimicrobial resistance profiles, carbapenemase and metallo-?-lactamase production, and their molecular characterization. Methods:A total of 186 clinical specimens were collected from 133 patients at various hospitals in Cairo, Egypt. The obtained specimens were subjected to bacteriological examination, antimicrobial susceptibility testing, detection of carbapenemase production using the modified Hodge test (MHT), the metallo-?-lactamase production using the EDTA combined disc test (CDT), and PCR-based detection of the bla KPC and bla GES resistance genes. The identification of the highly resistant retrieved isolates was then confirmed by 16S rRNA gene sequencing. Results:The most common isolated Gram-negative species was Klebsiella pneumoniae (40.9%), followed by Acinetobacter baumannii (18.8%), Pseudomonas aeruginosa (17.3%), Escherichia coli (15.4%), Enterobacter aerogenes (5.3%), and Proteus mirabilis (2.4%). The prevalence of carbapenem-resistant isolates was 36.1% (n=75). However, 86.5% of the recovered clinical isolates were susceptible to colistin. The MHT revealed that 33.6% (n=70) of the tested strains were positive for carbapenemase production, while the CDT showed that 33.17% (n=69) of the examined strains were metallo-?-lactamase producers. The PCR revealed that 98.6% (74/75) of the tested strains possessed the bla KPC gene; moreover, 97.3% (73/75) of the examined strains harbored the bla GES gene. Conclusion:This study displayed the emergence of carbapenem-resistant Gram-negative pathogens incriminated in healthcare-associated infections. The accurate identification of carbapenem-resistant bacterial pathogens is pivotal for the treatment of patients, in addition to propelling appropriate contamination control measures to restrain the fast spread of such pathogens. Colistin showed a potent in vitro antimicrobial activity against the carbapenem-resistant strains.

Dataset Information

Tracking colistin-treated patients to monitor the incidence and outcome of carbapenem-resistant Gram-negative infections.

Publications

Tracking colistin-treated patients to monitor the incidence and outcome of carbapenem-resistant Gram-negative infections.

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