Dataset Information

Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and ?-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus.

ABSTRACT: Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to ?-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two ?-lactams among 58 clinical MRSA bloodstream isolates. Of note, ?75% and ?36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic ?-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA.

SUBMITTER: Ersoy SC

PROVIDER: S-EPMC7179597 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus.

Ersoy Selvi C SC Otmishi Mariam M Milan Vanessa T VT Li Liang L Pak Youngju Y Mediavilla Jose J Chen Liang L Kreiswirth Barry B Chambers Henry F HF Proctor Richard A RA Xiong Yan Q YQ Fowler Vance G VG Bayer Arnold S AS

Antimicrobial agents and chemotherapy 20200421 5

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin ( ...[more]

PMID: 32041719

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Project description:The outcome of bacterial infection management relies on prompt diagnosis and effective treatment, but conventional antimicrobial susceptibility testing can be slow and labor-intensive. Therefore, this study aims to predict phenotypic antimicrobial susceptibility of selected beta-lactam antimicrobials in the bacteria of the family Enterobacteriaceae from different beta-lactamase resistance genotypes. Using human datasets extracted from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program conducted by Pfizer and retail meat datasets from the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS), we used a robust or weighted least square multivariable linear regression modeling framework to explore the relationship between antimicrobial susceptibility data of beta-lactam antimicrobials and different types of beta-lactamase resistance genes. In humans, in the presence of the blaCTX-M-1, blaCTX-M-2, blaCTX-M-8/25, and blaCTX-M-9 groups, MICs of cephalosporins significantly increased by values between 0.34-3.07 μg/mL, however, the MICs of carbapenem significantly decreased by values between 0.81-0.87 μg/mL. In the presence of carbapenemase genes (blaKPC, blaNDM, blaIMP, and blaVIM), the MICs of cephalosporin antimicrobials significantly increased by values between 1.06-5.77 μg/mL, while the MICs of carbapenem antimicrobials significantly increased by values between 5.39-67.38 μg/mL. In retail meat, MIC of ceftriaxone increased significantly in the presence of blaCMY-2, blaCTX-M-1, blaCTX-M-55, blaCTX-M-65, and blaSHV-2 by 55.16 μg/mL, 222.70 μg/mL, 250.81 μg/mL, 204.89 μg/mL, and 31.51 μg/mL respectively. MIC of cefoxitin increased significantly in the presence of blaCTX-M-65 and blaTEM-1 by 1.57 μg/mL and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of cefoxitin increased by an average of 8.66 μg/mL over 17 years. Compared to E. coli isolates, MIC of cefoxitin in Salmonella enterica isolates decreased significantly by 0.67 μg/mL. On the other hand, MIC of ceftiofur increased in the presence of blaCTX-M-1, blaCTX-M-65, blaSHV-2, and blaTEM-1 by 8.82 μg/mL, 9.11 μg/mL, 8.18 μg/mL, and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of ceftiofur increased by an average of 10.20 μg/mL over 14 years. The ability to predict antimicrobial susceptibility of beta-lactam antimicrobials directly from beta-lactamase resistance genes may help reduce the reliance on routine phenotypic testing with higher turnaround times in diagnostic, therapeutic, and surveillance of antimicrobial-resistant bacteria of the family Enterobacteriaceae.

Project description:Importance:Allergy to ?-lactam antibiotics is one of the most frequently reported drug reactions, but epidemiological data in Chinese populations are lacking. Ethnic- and region-specific sensitization patterns of skin testing for ?-lactam antibiotic allergy are also unknown. Objective:To identify the prevalence, 1-year incidence, and sensitization patterns of ?-lactam antibiotic allergy in patients in Hong Kong. Design, Setting, and Participants:This cross-sectional study obtained territorywide, anonymized electronic patient data from the Clinical Management Systems of the Hospital Authority, the sole publicly funded health care system in Hong Kong with facilities in 7 regions (Hong Kong East, Hong Kong West, Kowloon Central, Kowloon East, Kowloon West, New Territories East, and New Territories West). All referrals to Queen Mary Hospital for ?-lactam antibiotic allergy testing from January 1, 2018, to December 31, 2019, were also analyzed for sensitization patterns. Main Outcomes and Measures:Prevalence and cumulative incidence of ?-lactam antibiotic allergy reported in Hong Kong, and sensitization patterns according to ?-lactam antibiotic allergy skin testing. Results:Complete records of 7?184?271 unique patients were analyzed, with a men to women ratio of 1:1.2 and with a median age of 44 years. The prevalence of physician-reported ?-lactam antibiotic allergy was 2.0%, and the cumulative incidence was 107 per 100?000 population. Of the 34?402 new drug allergies reported in 2018, 8032 (23.3%) were ?-lactam antibiotic allergies. Three hundred fifty-five patients with reactions suggestive of ?-lactam antibiotic allergy underwent skin testing, and only 49 (13.8%; 95% CI, 10.64%-17.90%) of them had positive test results. Of these 49 patients, 14 (28.6%; 95% CI, 18.35%-44.49%) had selective reaction and 35 (71.4%; 95% CI, 59.84%-85.27%) had nonselective reaction. The sensitization rate to either benzylpenicilloyl polylysine or a minor determinant (benzylpenicilloate) was 47.0% (n?=?23; 95% CI, 34.85%-63.21%), with 10 patients monosensitized to benzylpenicilloyl polylysine only (20.4%; 95% CI, 11.74%-35.48%) and 5 to benzylpenicilloate only (10.2%; 95% CI, 4.45%-23.42%). Conclusions and Relevance:Results of this study suggest that patients in Hong Kong with ?-lactam antibiotic allergy had much higher rates of monosensitization to benzylpenicilloyl polylysine and benzylpenicilloate, making these reagents essential in ?-lactam antibiotic skin tests. Such a finding warrants future studies into whether this sensitization is specific to ethnicity or region.

Dataset Information

Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and ?-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus.

Publications

Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO<sub>3</sub>) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus.

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