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1.
Transpl Infect Dis ; 24(5): e13886, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35751866

ABSTRACT

BACKGROUND: Antibiotic stewardship programs (ASPs) are well established in the public hospitals in Singapore, but they are not mandatory for transplant programs. Given the positive impact of ASPs in non-organ transplant patients (improved use of broad-spectrum antibiotics, reduced length of stay, and lower healthcare costs), stewardship principles are likely to benefit transplant recipients. METHODS: We reviewed the progress made in ASPs in the Asia Pacific region as well as the progress of our ASP over the last decade since it was established. We also described how stewardship strategies have evolved for the purposes of our transplant program. RESULTS: Currently, pressing stewardship issues for our transplant program include high antibiotic consumption, as well as the burden, morbidity, and mortality associated with drug-resistant bacterial infections. Transplanting the model of stewardship onto a transplant program ignores the intricacies of transplant patients; the bespoke form of stewardship, "handshake stewardship", is more appropriate. CONCLUSION: To advance the cause of ASP in the transplant unit in Singapore, stakeholder buy-in is key; empowering transplant physicians to be stewardship-focused would be more sustainable in the long run. In addition, expanding our diagnostic armamentarium, optimizing existing therapeutics and multi-disciplinary team involvement (including stakeholders from microbiology, and infection prevention teams) are vital.


Subject(s)
Antimicrobial Stewardship , Bacterial Infections , Organ Transplantation , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/microbiology , Humans , Organ Transplantation/adverse effects , Singapore
2.
Int J Antimicrob Agents ; 56(5): 106145, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32860880

ABSTRACT

Healthcare resources are being diverted for the containment and control of coronavirus disease 2019 (COVID-19). During this outbreak, it is cautioned that antibiotic misuse may be increased, especially for respiratory tract infections. With stewardship interventions, the duration of antibiotic therapy and length of stay of hospitalized patients can be reduced significantly. Antibiotic stewardship programmes should continually engage and educate prescribers to mitigate antibiotic misuse during the COVID-19 pandemic.


Subject(s)
Antimicrobial Stewardship/methods , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Drug Misuse/prevention & control , Pneumonia, Viral/drug therapy , Betacoronavirus/drug effects , COVID-19 , Humans , Length of Stay , Pandemics , SARS-CoV-2
3.
Article in English | MEDLINE | ID: mdl-32571821

ABSTRACT

The increase of carbapenem-resistant Enterobacterales (CRE) and lack of therapeutic options due to the scarcity of new antibiotics has sparked interest toward the use of intravenous fosfomycin against systemic CRE infections. We aimed to investigate the in vitro pharmacodynamics of fosfomycin against carbapenem-resistant Enterobacter cloacae and Klebsiella aerogenes Time-kill studies and population analysis profiles were performed with eight clinical CRE isolates, which were exposed to fosfomycin concentrations ranging from 0.25 to 2,048 mg/liter. The 24-h mean killing effect was characterized by an inhibitory sigmoid maximum effect (Emax) model. Whole-genome sequencing was performed to elucidate known fosfomycin resistance mechanisms. Fosfomycin MICs ranged from 0.5 to 64 mg/liter. The isolates harbored a variety of carbapenemase genes including blaIMP, blaKPC, and blaNDM Five out of eight isolates harbored the fosA gene, while none harbored the recently discovered fosL-like gene. Heteroresistant subpopulations were detected in all isolates, with two out of eight isolates harboring heteroresistant subpopulations at up to 2,048 mg/liter. In time-kill studies, fosfomycin exhibited bactericidal activity at 2 to 4 h at several fosfomycin concentrations (one isolate at ≥16 mg/liter, two at ≥32 mg/liter, two at ≥64 mg/liter, two at ≥128 mg/liter, and one at ≥512 mg/liter). At 24 h, bactericidal activity was only observed in two isolates (MICs, 0.5 and 4 mg/liter) at 2,048 mg/liter. From the Emax model, no significant bacterial killing was observed beyond 500 mg/liter. Our findings suggest that the use of fosfomycin monotherapy may be limited against CRE due to heteroresistance and rapid bacterial regrowth. Further optimization of intravenous fosfomycin dosing regimens is required to increase efficacy against such infections.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Enterobacter aerogenes , Fosfomycin , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenems/pharmacology , Enterobacter cloacae/genetics , Fosfomycin/pharmacology , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , beta-Lactamases/genetics
4.
PLoS One ; 13(11): e0208039, 2018.
Article in English | MEDLINE | ID: mdl-30485357

ABSTRACT

BACKGROUND: Rising antibiotic resistance poses a challenge to the management of febrile neutropenia in patients with haematological malignancies receiving chemotherapy. AIM: We studied an alternating first-line antibiotic strategy to determine its impact on all-cause mortality and bacteremia rates in patients with febrile neutropenia. METHODS: An 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. FINDINGS: There 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. CONCLUSION: An alternating first-line antibiotic strategy resulted in an increase in antibiotic heterogeneity, without increasing mortality. There was also no significant increase in bacteremia rates.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Febrile Neutropenia/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/drug therapy , Bacteremia/mortality , Child , Drug Resistance, Bacterial , Febrile Neutropenia/mortality , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Humans , Male , Middle Aged , Practice Patterns, Physicians' , Treatment Outcome , Young Adult
5.
Case Rep Infect Dis ; 2014: 573279, 2014.
Article in English | MEDLINE | ID: mdl-24995135

ABSTRACT

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.

6.
PLoS One ; 7(12): e51605, 2012.
Article in English | MEDLINE | ID: mdl-23251592

ABSTRACT

BACKGROUND: In 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. AIM: The 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. METHODS: Based 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. FINDINGS: Tissue incubation at 4°C for 24 hours is optimal for both antibiotics, especially for amikacin, as its potency falls drastically at 37°C. CONCLUSION: The 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.


Subject(s)
Amikacin/pharmacology , Anti-Bacterial Agents/pharmacology , Blood Vessel Prosthesis/microbiology , Decontamination/methods , Penicillins/pharmacology , Streptomycin/pharmacology , Vancomycin/pharmacology , Bacteria/drug effects , Bacteria/isolation & purification , Humans , Microbial Sensitivity Tests , Singapore , Temperature , Time Factors , Transplantation, Homologous
7.
Antimicrob Agents Chemother ; 55(1): 436-8, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20956606

ABSTRACT

This study examined the in vitro effects of polymyxin B, tigecycline, and rifampin combinations on 16 isolates of extensively drug-resistant Acinetobacter baumannii, including four polymyxin-resistant strains. In vitro synergy was demonstrated in 19 (40%) of a possible 48 isolate-antibiotic combinations by time-kill methods, 8 (17%) by checkerboard methods, and only 1 (2%) by Etest methods. There was only slight agreement between Etest and checkerboard methods and no agreement between results obtained by other methods.


Subject(s)
Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Drug Synergism , Microbial Sensitivity Tests , Minocycline/analogs & derivatives , Minocycline/pharmacology , Polymyxin B/pharmacology , Rifampin/pharmacology , Tigecycline
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