The epidemiological impact and significance of carbapenem resistance in Pseudomonas aeruginosa bloodstream infections: a matched case-case-control analysis.

A case-case-control investigation (N = 255 patients) explored the epidemiology of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Recent exposure to carbapenems and a rapidly fatal condition should prompt practitioners to shorten delays in initiating appropriate therapy, which can adversely impact CRPA outcomes, as opposed to the isolated impact of the carbapenem resistance determinant.

Towards a Definition for Health Care-Associated Infection.

BACKGROUND: Health care-associated infection (HcAI) is a term frequently used to describe community-onset infections likely to be caused by multidrug-resistant organisms (MDROs). The most frequently used definition was developed at Duke University Medical Center in 2002 (Duke-2002). Although some professional societies have based management recommendations on Duke-2002 (or modifications thereof), neither Duke-2002 nor other variations have had their performance measured. METHODS: A case-control study was conducted at Assaf Harofeh Medical Center (AHMC) of consecutive adult bloodstream infections (BSIs). A multivariable model was used to develop a prediction score for HcAI, measured by the presence of MDRO infection on admission. The performances of this new score and previously developed definitions at predicting MDRO infection on admission were measured. RESULTS: Of the 504 BSI patients enrolled, 315 had a BSI on admission and 189 had a nosocomial BSI. Patients with MDRO-BSI on admission (n = 100) resembled patients with nosocomial infections (n = 189) in terms of epidemiological characteristics, illness acuity, and outcomes more than patients with non-MDRO-BSI on admission (n = 215). The performances of both the newly developed score and the Duke-2002 definition to predict MDRO infection on admission were suboptimal (area under the receiver operating characteric curve, 0.76 and 0.68, respectively). CONCLUSIONS: Although the term HcAI is frequently used, its definition does not perform well at predicting MDRO infection present on admission to the hospital. A validated score that calculates the risk of MDRO infection on admission is still needed to guide daily practice and improve patient outcomes.

[THE EPIDEMIOLOGY OF CLOSTRIDIUM DIFFICILE INFECTIONS AND ASPECTS PERTAINING TO TREATMENT WITH VANCOMYCIN AT ASSAF HAROFEH MEDICAL CENTER].

BACKGROUND: The epidemiology of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI. However, controlled comparative data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent vancomycin-resistant Enterococcus (VRE) isolation remains unknown. METHODS: A retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, from 2013 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs. metronidazole among patients with mild CDI, and the independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation, was analyzed by logistic regression. RESULTS: A total of 260 patients with CDI were enrolled. The majority were elderly (75%), and 56% had moderate to severe disease. Among 75 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a "vancomycin case". In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=74, p=0.004). CONCLUSIONS: Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis.

Therapeutic Management of Pseudomonas aeruginosa Bloodstream Infection Non-Susceptible to Carbapenems but Susceptible to "Old" Cephalosporins and/or to Penicillins.

It is unknown as to whether other beta-lactams can be used for bloodstream infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non-susceptible to one or more carbapenem. We conducted a retrospective cohort study at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014. Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but susceptible to ceftazidime or piperacillin (with or without tazobactam), were enrolled. We compared the outcomes of patients who received an appropriate beta-lactam antibiotic ("cases") to those who received an appropriate non-beta-lactam antibiotic ("controls"). Whole genome sequencing was performed for one of the isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and one colistin and an aminoglycoside). All clinical outcomes were similar between the groups. There were large variations in the phenotypic susceptibilities of the strains. A detailed molecular investigation of one isolate revealed a strain that belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene was intact. Non-carbapenem-ß-lactams may still be effective alternatives for short duration therapy (up to 14 days) for BSI caused by a carbapenem non-susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin-tazobactam) PA strain. This observation requires further confirmatory analyses. Future molecular investigations should be performed, in order to further analyze additional potential mechanisms for this prevalent phenotype.

Intra-abdominal Infections: The Role of Anaerobes, Enterococci, Fungi, and Multidrug-Resistant Organisms.

BACKGROUND: Intra-abdominal infections (IAI) constitute a common reason for hospitalization. However, there is lack of standardization in empiric management of (1) anaerobes, (2) enterococci, (3) fungi, and (4) multidrug-resistant organisms (MDRO). The recommendation is to institute empiric coverage for some of these organisms in "high-risk community-acquired" or in "healthcare-associated" infections (HCAI), but exact definitions are not provided. METHODS: Epidemiological study of IAI was conducted at Assaf Harofeh Medical Center (May-November 2013). Logistic and Cox regressions were used to analyze predictors and outcomes of IAI, respectively. The performances of established HCAI definitions to predict MDRO-IAI upon admission were calculated by receiver operating characteristic (ROC) curve analyses. RESULTS: After reviewing 8219 discharge notes, 253 consecutive patients were enrolled (43 [17%] children). There were 116 patients with appendicitis, 93 biliary infections, and 17 with diverticulitis. Cultures were obtained from 88 patients (35%), and 44 of them (50%) yielded a microbiologically confirmed IAI: 9% fungal, 11% enterococcal, 25% anaerobic, and 34% MDRO. Eighty percent of MDRO-IAIs were present upon admission, but the area under the ROC curve of predicting MDRO-IAI upon admission by the commonly used HCAI definitions were low (0.73 and 0.69). Independent predictors for MDRO-IAI were advanced age and active malignancy. CONCLUSIONS: Multidrug-resistant organism-IAIs are common, and empiric broad-spectrum coverage is important among elderly patients with active malignancy, even if the infection onset was outside the hospital setting, regardless of current HCAI definitions. Outcomes analyses suggest that empiric regimens should routinely contain antianaerobes (except for biliary IAI); however, empiric antienterococcal or antifungals regimens are seldom needed.

Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections.

Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems.

Diabetic foot infection in hospitalized adults.

BACKGROUND: Acute infections of the diabetic foot (DFI) are a common and complex condition. Patients are generally managed in the ambulatory setting and epidemiological data pertaining to hospitalized patients is lacking. The aim of this study was to analyze the epidemiology, microbiology and outcomes of hospitalized patients with DFI, who are managed at a referral center equipped with hyperbaric oxygen (HBO) therapy. METHODS: A retrospective cohort study of adult patients admitted to a tertiary referral center with DFI over a six-month period in 2013 was undertaken. Predictors of clinical outcomes and efficacy of treatment modalities were analyzed by Cox regression. RESULTS: Sixty-one patients with DFI were identified. Most patients were elderly (67 ± 13 years), with long-standing (17 ± 9 years), poorly controlled (HbA1c 9 ± 3%) diabetes. Most patients had polymicrobial infection (80%); specifically, anaerobic (39%) and multi or extensively-drug resistant organisms (61%). Administration of appropriate antimicrobials was delayed for >48 h in 83%. Advanced age was associated with worse outcomes. Sicker patients with severe peripheral vascular disease were managed with HBO. The use of HBO was associated with higher costs and increased functional deterioration, and did not prevent future limb amputation. CONCLUSIONS: Our study illustrates the descriptive epidemiology of hospitalized adults with DFI predominantly of polymicrobial etiology. MDROs and anaerobic organisms are common causative pathogens, and appropriate antibiotics were frequently delayed. HBO treatment may delay the need for limb amputation, but not obviate this eventual outcome.