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New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for β-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. Twenty β-lactam antigens were produced using human serum albumin and histone H1 as carrier proteins. Antigens were tested by multiplex in vitro immunoassays and evaluated based on the detection of specific IgG and IgE in the serum samples. Both major and minor determinants were appropriate antigens for detecting specific anti-β-lactam IgG in immunised rabbit sera. In a cohort of 37 allergic patients, we observed that only the minor determinants (-llanyl antigens) were suitable for determining specific anti-β-lactam IgE antibodies with high sensitivity (< 0.01 IU/mL; 24 ng/L) and specificity (100%). These findings reveal that not only the haptenisation of β-lactam antibiotics renders improved molecular recognition events when the 4-member β-lactam ring remains unmodified, but also may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions. This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam.

Gram negative anaerobic organisms are important pathogens in a range of clinical infections, and susceptibility testing is not commonly performed in the microbiology laboratory. We performed anaerobic susceptibility testing on 70 clinically relevant Gram negative anaerobes isolated from routine cultures in a busy diagnostic laboratory which were identified by MALDI-TOF mass spectrometry (MALDI-TOF MS). The susceptibility testing was performed by two methods: Sensititre trays (ThermoFisher Scientific) against 15 different antibiotics, and Etests (bioMérieux) against five clinically relevant antibiotics (metronidazole, piperacillin-tazobactam, amoxicillin-clavulanate, meropenem and clindamycin). We found that all isolates were susceptible to metronidazole, and overall susceptibility to commonly used antibiotics such as piperacillin-tazobactam and amoxicillin-clavulanate was high (93-100% and 89-100%, respectively). Two isolates of Bacteroides fragilis were resistant to both broad spectrum β-lactams and carbapenems. Comparing the two methods, using Sensititre broth microdilution as gold standard, there was high categorical agreement (92-100%). Antibiograms provide useful information for clinicians when choosing antimicrobials for infections caused by anaerobic organisms. This study has shown that in our area, use of metronidazole as a broad spectrum anti-anaerobic agent remains appropriate. Anaerobic susceptibility testing is also important to perform in individual clinical isolates, especially from sterile sites or in pure culture. The emergence of broad spectrum β-lactam and carbapenem resistance in clinical isolates of Bacteroides fragilis is of concern and will require further monitoring. The Etest method was considered superior to Sensititre trays given that the higher inoculum used may allow demonstration of heteroresistance, anaerobiasis can be maintained during setup, lower failure rates, and the ability to select only the antibiotics required., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: There are no studies on cross-reactivity of betalactams among patients allergic to penicillin, or on the negative predictive value (NPV) of penicillin allergy evaluation from Arabian Gulf countries., Objective: We aimed to assess the role and NPV of drug provocation test (DPT) for betalactam hypersensitivity reactions in patients referred for allergy evaluation in Kuwait., Methods: Skin test (ST) was performed for all patients with a history of betalactam hypersensitivity, other than anaphylaxis. Patients with a negative ST were challenged with a DPT containing phenoxymethyl penicillin or the culprit drug. Patients with anaphylaxis or who tested positive to betalactams were then challenged with a DPT containing cefuroxime, meropenem or ceftriaxone. Patients who tested negative were contacted by phone to evaluate subsequent betalactam intake., Results: A total of 214 patients were tested for betalactam hypersensitivity. We had 91(42.5%) positive cases. Among positives, there were 78 (85.7%) patients with an initial reaction to penicillin and 13 (14.3%) who reacted to cephalosporin. DPT with alternative betalactam was performed in fifty who tested positive for betalactam hypersensitivity and 45 (90%) tolerated alternative antibiotics. Phone calls to 113 (59.8%) patients with negative betalactam testing showed that among 40(35.4%) patients who were successfully contacted; 17 (15%) took betalactams and 23 (20%) did not. Among the 17 patients who took betalactams, our calculated NPV for penicillin testing range from 88.2 to 100%, as the 2 patients who reported a reaction refused confirmatory retesting., Conclusion: Carbapenems and cephalosporines can be safely given to penicillin allergic patients by means of skin testing and if negative, proceeding with a graded challenge. Our calculated NPV for penicillin testing is similar to other studies.

Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County health-care facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections is increasing in the United States. However, few studies have addressed their epidemiology in children. To phenotypically identify CRE isolates cultured from patients 1-17 years of age, we used antimicrobial susceptibilities of Enterobacteriaceae reported to 300 laboratories participating in The Surveillance Network-USA database during January 1999-July 2012. Of 316,253 isolates analyzed, 266 (0.08%) were identified as CRE. CRE infection rate increases were highest for Enterobacter species, blood culture isolates, and isolates from intensive care units, increasing from 0.0% in 1999-2000 to 5.2%, 4.5%, and 3.2%, respectively, in 2011-2012. CRE occurrence in children is increasing but remains low and is less common than that for extended-spectrum β-lactamase-producing Enterobacteriaceae. The molecular characterization of CRE isolates from children and clinical epidemiology of infection are essential for development of effective prevention strategies.

Objective: To devise a local strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae (CRKP)., Design: Quasi-experimental, before-and-after, interrupted time-series study., Setting: A 1,000-bed tertiary-care university teaching hospital., Methods: Retrospectively, all relevant data were collected from the medical records of patients with CRKP infections from May 2006 through April 2007, the preintervention period. From May 1, 2007, through May 1, 2010, the postintervention period, the intervention was applied and prospectively followed. The 5 key elements of this strategy were an emergency department flagging system, the building of a cohort ward, the eradication of clusters, environmental and personnel hand cultures, and a carbapenem-restriction policy. The demographic and clinical parameters of patients colonized by and/or infected with CRKP were collected from medical records., Results: A total of 10,680 rectal cultures were performed for 8,376 patients; 433 (5.16%) and 370 (4.4%) were CRKP-colonized and CRKP-infected patients, respectively, and 789 (98%) of 803 patients were admitted to the CRKP cohort ward. The CRKP infection density was reduced from 5.26 to 0.18 per 10,000 patient-days (P ≤ .001), and no nosocomial CRKP infections were diagnosed. Twenty-three percent of environmental cultures were found to be positive. Meropenem use was reduced from 283 ± 70.92 to 118 ± 74.32 defined daily doses per 1,000 patient-days (P ≤ .001)., Conclusion: This intervention produced an enormous impact on patient location, surveillance cultures, and antibiotic policies and a massive investment in infection control resources.

Background: There have been few studies regarding the cross-reactivity and tolerability of penicillins, aztreonam, and carbapenems in large samples of subjects with cephalosporin allergy., Objective: We sought to evaluate the possibility of using penicillins, monobactams, and carbapenems in subjects with cephalosporin allergy who especially require them., Methods: We conducted a prospective study of 98 consecutive subjects who had 106 immediate reactions (mostly anaphylactic shock) to cephalosporins and had positive skin test results for these drugs. To assess the cross-reactivity with penicillins, monobactams, and carbapenems and the tolerability of such alternative β-lactams, all subjects underwent skin tests and serum-specific IgE assays with penicillin reagents, as well as skin tests with aztreonam, imipenem/cilastatin, and meropenem. Subjects with negative test results were challenged with meropenem, imipenem/cilastatin, aztreonam, and amoxicillin., Results: Positive allergologic test results to penicillins were displayed by 25 (25.5%) subjects, including 1 with positive results to all reagents tested and another with a positive result to aztreonam. Another subject had positive results to both ceftazidime and aztreonam. A reaction to cephalosporins with side-chain structures similar or identical to those of penicillins was a significant predictor of cross-reactivity because of an increased 3-fold risk of positive results on allergologic tests with penicillin determinants. Challenges with alternative β-lactams were tolerated, with the exception of 1 urticarial reaction to imipenem/cilastatin., Conclusions: About 25% of subjects with cephalosporin allergy had positive results to penicillins, 3.1% to aztreonam, 2% to imipenem/cilastatin, and 1% to meropenem. In those who especially require alternative β-lactams, pretreatment skin tests are advisable because negative results indicate tolerability of the β-lactam concerned., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objective: To evaluate the literature on the allergic cross-reactivity between penicillin, carbapenem, and monobactam antibiotics., Data Sources: A MEDLINE search (1950-June 2008) of the English literature was performed using the search terms beta-lactam, penicillin, monobactam, carbapenem, allergy, and cross-reactivity. References of review articles were also screened for inclusion., Study Selection and Data Extraction: All articles in English from the data source were identified. Studies whose primary goal was to evaluate drug hypersensitivity and the potential for cross-reactivity were evaluated., Data Synthesis: Many patients have reported penicillin allergies that have not been verified by skin testing; many healthcare providers avoid the use of other beta-lactam antibiotics, namely carbapenems, in these patients due to fear of the potential for immunoglobulin E-mediated allergic cross-reactivity. A wide range of cross-reactivity between penicillins and carbapenems has been reported in various studies; however, more recent prospective studies have shown the incidence of cross-reactivity between penicillin and carbapenem skin tests to be around 1%. Additionally, many prescribers freely use the monobactam aztreonam in penicillin-allergic patients, believing there is no cross-reactivity between the 2 drugs. Although data support the lack of cross-reactivity between aztreonam and penicillins, immunology and some clinical data support an interaction between ceftazidime and aztreonam due to the similarity of their side chains., Conclusions: Although variability in cross-reactivity rates between beta-lactam classes exists in the literature, the practice of avoiding carbapenems in penicillin-allergic patients should be reconsidered. With regard to monobactams, the administration of aztreonam in a patient with a ceftazidime allergy may carry an increased risk of type 1 hypersensitivity reactions and should be considered with caution. Additionally, the importance of obtaining a thorough patient history regarding the previous allergic event, proper documentation, and penicillin skin testing is reemphasized.

A carbapenem antibiotic, L-786,392, was designed so that the side chain that provides high-affinity binding to the penicillin-binding proteins responsible for bacterial resistance was also the structural basis for ameliorating immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring retained antibacterial activity while safely expelling the immunodominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci.