Highlights During the COVID-19 outbreak, antibiotic use has increased, especially respiratory antibiotics. Healthcare resources are diverted to containment and management of COVID-19 cases, but the efforts of antibiotic stewardship programmes (ASPs) must run in parallel to mitigate antibiotic misuse and antimicrobial resistance. ASPs must be operationally adaptable, and possess robust surveillance systems that detect subtle changes in prescribing and resistance trends. This is an opportunity to execute a syndromic approach to guide antibiotic prescribing. Continued engagement and education of prescribers to ensure appropriate prescription of antibiotics is important.

Treatment of extensively drug-resistant (XDR) Acinetobacter baumannii infections is challenging because of both the limited choice of antibiotic and the tendency of such infections to occur in critically ill hosts with limited physiologic reserves (17). Polymyxins demonstrate in vitro activity against A. baumannii, but resistance is also reported (8,17). In the absence of feasible alternatives, unconventional antibiotics, such as minocycline, rifampin, and tigecycline, have been used, both singly and in combination (19). In vitro combination susceptibility testing poses a significant challenge for clinical microbiology laboratories, with a lack of standardization and a variety of in vitro testing methods. This study evaluated the effects of various antibiotic combinations against a panel of XDR-Acinetobacter baumannii and compared in vitro synergy testing results obtained from time-kill, checkerboard, and Etest methods.(Some elements of this study were presented at the 20th European Congress of Clinical Microbiology and Infectious Diseases, 2010.) Clinical isolates of antibiotic-resistant A. baumannii were collected from four hospitals in Singapore over a 2-year period. Species identification was confirmed by a multiplex PCR assay (2). MICs to ampicillin-sulbactam, ciprofloxacin, gentamicin, imipenem, meropenem, aztreonam, piperacillin-tazobactam, polymyxin B, tigecycline, ceftazidime, amikacin, and cefepime were obtained by broth microdilution (Sensititre, Trek Diagnostics, United Kingdom), while MICs for rifampin were obtained by broth macrodilution (3). Categorical susceptibility was based on Clinical and Laboratory Standards Institute breakpoints (4). XDR A. baumannii isolates were defined as isolates that were resistant to all the tested antimicrobials except for tigecycline, rifampin, and polymyxin B (5, 6), while pandrug-resistant (PDR) A. baumannii was resistant to all tested antimicrobial agents (5, 6). Clonal relatedness of study isolates was determined by multiplex PCR strain typing (11), with cluster analysis of banding data performed using the unweighted pair group method with arithmetic mean.All strains were tested for the presence of in vitro synergy to polymyxin B-rifampin, polymyxin B-tigecycline, and tigecycline-rifampin combinations by three methods. These combinations were selected based on previously published data, which demonstrated a high likelihood of achieving in vitro synergy (10). Time-kill assays were performed following methods published by the Clinical and Laboratory Standards Institute (13), with colony enumeration performed at 0-and 24-h time points. The lower limit of detection was 400 CFU/ml. Antibiotic concentrations used for the time-kill assay were 2 mg/liter for each antibiotic, representing achievable serum concentrations for polymyxin B (9) and rifampin (7) and achievable tissue levels for tigecycline (18).Etest and checkerboard synergy testing were performed according to published methods (12,20). Fractional inhibitory concentrations (FIC) were calculated as follows: ...

BackgroundRising antibiotic resistance poses a challenge to the management of febrile neutropenia in patients with haematological malignancies receiving chemotherapy.AimWe studied an alternating first-line antibiotic strategy to determine its impact on all-cause mortality and bacteremia rates in patients with febrile neutropenia.MethodsAn alternating first-line antibiotic strategy was established in mid-2013. Data for 2012 (before strategy implementation) and 2014 (post-strategy implementation) were compared. Antibiotic Heterogeneity Index (AHI) for each of the two time-periods was also calculated.FindingsThere were 2012 admissions (26082 patient-days) in 2012 and 1843 admissions (24331 patient-days) in 2014. There was no significant difference in the baseline characteristics of patients in the two groups. The defined daily doses (DDD) of cefepime (CEF) fell while the DDD of piperacillin-tazobactam (PTZ) rose in 2014 compared with 2012. Vancomycin DDD fell in 2014. The AHI was 0.466 in 2012 and 0.582 in 2014. The difference in all-cause mortality was not statistically significant. There was no difference in rates of bacteremia with CEF-resistant, PTZ-resistant and carbapenem-resistant gram-negative organisms in the two groups. Rates of new cases of Methicillin-resistant Staphylococcus aureus (MRSA) were 2.38/1000 and 2.59/1000 patient-days in 2012 and 2014 respectively. Rates of new cases of Vancomycin-resistant Enterococcus (VRE) were 1.84/1000 and 1.81/1000 patient-days in 2012 and 2014 respectively. There was no Carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in 2012 and 1 in 2014.ConclusionAn alternating first-line antibiotic strategy resulted in an increase in antibiotic heterogeneity, without increasing mortality. There was also no significant increase in bacteremia rates.

BackgroundIn February 2012, the National Cardiovascular Homograft Bank (NCHB) became the first tissue bank outside of North America to receive accreditation from the American Association of Tissue Banks. From 2008 to 2009, NCHB had been decontaminating its cardiovascular homografts with penicillin and streptomycin. The antibiotic decontamination protocol was changed in January 2010 as amikacin and vancomycin were recommended, in order to cover bacteria isolated from post-recovery and post- antibiotic incubation tissue cultures.AimThe objective of this study is to determine the optimal incubation conditions for decontamination of homografts by evaluating the potencies of amikacin and vancomycin in different incubation conditions. Retrospective reviews of microbiological results were also performed for homografts recovered from 2008 to 2012, to compare the effectiveness of penicillin-streptomycin versus the amikacin-vancomycin regimens.MethodsBased on microbiological assays stated in United States Pharmacopeia 31, potency of amikacin was evaluated by turbidimetric assay using Staphylococcus aureus, while vancomycin was by diffusion assay using Bacillus subtilis sporulate. Experiments were performed to investigate the potencies of individual antibiotic 6-hours post incubation at 4°C and 37°C and 4°C for 24 hours, after the results suggested that amikacin was more potent at lower temperature.FindingsTissue incubation at 4°C for 24 hours is optimal for both antibiotics, especially for amikacin, as its potency falls drastically at 37°C.ConclusionThe decontamination regimen of amikacin-vancomycin at 4°C for 24 hours is effective. Nevertheless, it is imperative to monitor microbiological trends closely and evaluate the efficacy of current antibiotics regimen against emerging strains of micro-organisms.

Recent pharmacokinetic studies have suggested that nonrenal clearance predominates the elimination of polymyxin B. We present 2 patients with preexisting end stage renal failure, who were given nonattenuated doses of polymyxin B for the treatment of extreme-drug resistant organism. No evidence of adverse events occurred and microbiological clearance was documented.