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: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.

Project description:Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as ?-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with ?-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with ?-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections.

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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