Beta-lactam antibiotics administration among adult inpatients with a beta-lactam allergy label: incidence, predictors, and outcomes.

Background: A beta-lactam antibiotics (BLA) allergy label is common, resulting in disadvantageous outcomes due to the usage of second-line antimicrobial agents. Noncontrolled case-series analyses report low rates of hypersensitivity reactions, following intentional/non-intentional BLA challenges among labeled inpatients. The study aims were to explore predictors and outcomes associated with hypersensitivity reactions following BLA challenge among BLA-allergic labeled inpatients. Methods: Retrospective cohort study (2019-2020) of adult (≥18 years) inpatients (Shamir Medical Center, Israel), labeled as allergic to ≥1 BLA, who received ≥1 dose/s of BLA during their stay. Independent predictors to develop allergic reactions and the independent associations of allergic reactions with clinical outcomes were queried by logistic and Cox regressions. Results: Of 9,670 inpatients (14,088 hospitalizations), 3,570 (37%) were labeled as allergic to ≥1 BLA. Of those, 1,171 (33%) patients received ≥1 BLA. The majority were women (67%), and the mean age was 69.3 ± 19.4 years. Only 30 patients (2.6%) developed a reaction, all mild. Independent predictors to develop an allergic reaction were documented reactions in the past, atopic background, antihistamines administration prior to the BLA challenge, and high risk for cross-reactivity, based on the BLA side chains, between the labeled and the challenged agents. Reaction upon the BLA challenge was not independently associated with any worse outcome. Conclusions: Despite the commonality of allergy labeling, and the commonality of BLA administration to labeled inpatients, hypersensitivity reactions were mild and rare. Interventional stewardship strategies for active BLA de-labeling among low-risk patients should be promoted, to improve patients' and institutional health and fiscal outcomes.

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.

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.

Risk Factors and Outcomes for Carbapenem-Resistant Klebsiella pneumoniae Isolation, Stratified by Its Multilocus Sequence Typing: ST258 Versus Non-ST258.

A "high risk" clone of carbapenem-resistant Klebsiella pneumoniae (CRKP) identified by multilocus sequence typing (MLST) as sequence type (ST) 258 has disseminated worldwide. As the molecular epidemiology of the CRE pandemic continues to evolve, the clinical impact of non-ST258 strains is less well defined. We conducted an epidemiological investigation of CRKP based on strains MLST. Among 68 CRKP patients, 61 were ST258 and 7 belonged to non-ST258. Klebsiella pneumoniae ST258 strains were significantly associated with bla KPC production and with resistance to an increased number of antimicrobials. Clinical outcomes were not different. Based on this analysis, one cannot rely solely on the presence of bla KPC in order to diagnose CRKP.

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.

The Complex Epidemiology of Carbapenem-Resistant Enterobacter Infections: A Multicenter Descriptive Analysis.

BACKGROUND: The pandemic of carbapenem-resistant Enterobacteriaceae (CRE) was primarily due to clonal spread of bla KPC producing Klebsiella pneumoniae. Thus, thoroughly studied CRE cohorts have consisted mostly of K. pneumoniae. OBJECTIVE: To conduct an extensive epidemiologic analysis of carbapenem-resistant Enterobacter spp. (CREn) from 2 endemic and geographically distinct centers. METHODS: CREn were investigated at an Israeli center (Assaf Harofeh Medical Center, January 2007 to July 2012) and at a US center (Detroit Medical Center, September 2008 to September 2009). bla KPC genes were queried by polymerase chain reaction. Repetitive extragenic palindromic polymerase chain reaction and pulsed-field gel electrophoresis were used to determine genetic relatedness. RESULTS: In this analysis, 68 unique patients with CREn were enrolled. Sixteen isolates (24%) were from wounds, and 33 (48%) represented colonization only. All isolates exhibited a positive Modified Hodge Test, but only 93% (27 of 29) contained bla KPC. Forty-three isolates (63%) were from elderly adults, and 5 (7.4%) were from neonates. Twenty-seven patients died in hospital (40.3% of infected patients). Enterobacter strains consisted of 4 separate clones from Assaf Harofeh Medical Center and of 4 distinct clones from Detroit Medical Center. CONCLUSIONS: In this study conducted at 2 distinct CRE endemic regions, there were unique epidemiologic features to CREn: (i) polyclonality, (ii) neonates accounting for more than 7% of cohort, and (iii) high rate of colonization (almost one-half of all cases represented colonization). Since false-positive Modified Hodge Tests in Enterobacter spp. are common, close monitoring of carbapenem resistance mechanisms (particularly carbapenemase production) among Enterobacter spp. is important.

Simple bedside score to optimize the time and the decision to initiate appropriate therapy for carbapenem-resistant Enterobacteriaceae.

BACKGROUND: Epidemiological characteristics of patients with bloodstream infections (BSI) due to extended-spectrum ß-lactamase producing (ESBL) and carbapenem-resistant (CRE) strains are often similar. Mortality rates for CRE BSI are 70%, and mean time to initiation of appropriate therapy is ~5 days. A bedside score was developed to differentiate CRE-BSIs from ESBL-BSIs, in order to help decrease the time to initiation of appropriate therapy for CRE and mortality rates. FINDINGS: Score was developed based of data (2007-2010) abstracted from charts of adult patients from Assaf Harofeh Medical Center (AHMC, Zeriffin, Israel), and validated on a cohort of patients from Detroit Medical Center (DMC, MI, USA). A multivariate model for presence of CRE was generated. A clinical prediction score and ROC curve was derived. 451 patients with ESBL BSIs (285 from AHMC and 166 from DMC) and 74 patients with CRE BSIs (58 from AHMC and 16 from DMC) were included. The prediction score included chemotherapy in the past 3 months (19 points), presence of foreign invasive devices (10 points), no peripheral vascular disease (10 points), reduced consciousness or cognition at time of acute illness (9 points), time in hospital prior to BSI ≥ 3 days (7 points), and age younger than 65 years (6 points). A score of ≥32 to define "high CRE risk" had sensitivity of 59%, specificity of 76%, PPV of 34% and NPV of 90%. CONCLUSIONS: The score's 90% NPV implies it could reduce un-necessary (and toxic) empiric use of anti-CRE therapeutics, but this should be studied prospectively and on broader populations in order to test its potential role in reducing mortality.

The complex epidemiology of extended-spectrum ß-lactamase-producing Enterobacteriaceae.

Antimicrobial resistance is a growing worldwide iatrogenic complication of modern medical care. Extended-spectrum ß-lactamases have emerged as one of the most successful resistance mechanisms, limiting our therapeutic options to treat various human infections. The dissemination of these enzymes to the community probably signifies an irreversible step. This paper will review the evolution of human infections associated with extended-spectrum ß-lactamase-producing organisms in the past 20 years, and will present and discuss the current challenges, controversies, debates and knowledge gaps in this research field.

Carbapenems Versus Piperacillin-Tazobactam for Bloodstream Infections of Nonurinary Source Caused by Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae.

A recent, frequently quoted study has suggested that for bloodstream infections (BSIs) due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL) Escherichia coli, treatment with ß-lactam/ß-lactamase inhibitors (BLBLIs) might be equivalent to treatment with carbapenems. However, the majority of BSIs originate from the urinary tract. A multicenter, multinational efficacy analysis was conducted from 2010 to 2012 to compare outcomes of patients with non-urinary ESBL BSIs who received a carbapenem (69 patients) vs those treated with piperacillin-tazobactam (10 patients). In multivariate analysis, therapy with piperacillin-tazobactam was associated with increased 90-day mortality (adjusted odds ratio, 7.9, P=.03). For ESBL BSIs of a non-urinary origin, carbapenems should be considered a superior treatment to BLBLIs.