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Microbiology Spectrum Jun 2022The oxacillin- and cefoxitin-susceptible -positive Staphylococcus aureus is a novel "stealth" methicillin-resistant S. aureus (MRSA) type. Here, we sequenced the whole...
The oxacillin- and cefoxitin-susceptible -positive Staphylococcus aureus is a novel "stealth" methicillin-resistant S. aureus (MRSA) type. Here, we sequenced the whole genome of two oxacillin- and cefoxitin-susceptible -positive MRSA isolates from breast abscesses in a lactating woman and a nasal swab of a healthy student in Guangzhou for investigating the mechanism underlying its occurrence. The reversion of these isolates was selected by exposure to sub-MICs of cefoxitin with or without mupirocin. The expression of both parental strains and their revertants was determined, and the whole genome of the revertants was sequenced. Comparative whole-genome analyses performed for both strains revealed that of the clinical strain was mutated by a single-bp insertion at the 262nd position in the tandem repeat region of the gene, and this mutation that led to the formation of a premature stop codon. The colonizing strain was mutated by a novel G-to-A base substitution in the second promoter region (-35 bp) of . The expression level of strain 697 revertant was 37 times higher than that of the parental strain. Although the expression level was even higher for parental strain 199 compared with that for its revertant, its cDNA sequence contained a single-bp insertion. Collectively, both the missense and single substitution mutations of the second promoter of could render MRSA isolates as "stealth" MRSA, thereby emphasizing the importance of combining phenotype tests with or penicillin-binding protein 2a detection for the identification of MRSA. The oxacillin- and cefoxitin-susceptible -positive Staphylococcus aureus is a novel type of "stealth" methicillin-resistant S. aureus (MRSA), which is difficult to be detected using conventional methods. To investigate the genomic basis of their occurrence, we sequenced the whole genome of two previously recovered oxacillin- and cefoxitin-susceptible -positive MRSA isolates from breast abscesses in a lactating woman and a nasal swab of a healthy student in Guangzhou. Complete SCC structure was absent except for in clinical isolate 199. Additionally, a novel single-base pair insertion was observed in the clinical strain, which resulted in premature termination and a frameshift mutation. The colonizing isolate 697 had a Scc--type IVa, and the second promoter region (-35 bp) of was mutated by a novel G-to-A base substitution. The reversion of oxacillin- and cefoxitin-susceptible -positive S. aureus to resistant MRSA isolates was selected by exposure to subminimum inhibitory cefoxitin with or without mupirocin.
Topics: Abscess; Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Female; Genomics; Humans; Lactation; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mupirocin; Oxacillin; Penicillin-Binding Proteins; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35608351
DOI: 10.1128/spectrum.00291-22 -
Journal of Clinical Microbiology Dec 2019Methicillin (β-lactam) resistance in is mediated by the gene, with resistance reported to be as high as 90%. The goal of this study was to evaluate oxacillin and...
Evaluation of Oxacillin and Cefoxitin Disk Diffusion and Microbroth Dilution Methods for Detecting -Mediated β-Lactam Resistance in Contemporary Staphylococcus epidermidis Isolates.
Methicillin (β-lactam) resistance in is mediated by the gene, with resistance reported to be as high as 90%. The goal of this study was to evaluate oxacillin and cefoxitin disk diffusion (DD) and broth microdilution (BMD) methods for the detection of -mediated β-lactam resistance in 100 human isolates of (48 -positive isolates and 52 negative isolates). Oxacillin DD tests using the Clinical and Laboratory Standards Institute (CLSI) M100-S28 breakpoints for / accurately differentiated -positive and -negative isolates, with categorical agreement (CA) of 100% and no very major errors (VMEs) or major errors (MEs) identified. Likewise, oxacillin BMD and cefoxitin DD tests using the coagulase-negative species (CoNS) breakpoints were highly reliable for detecting -mediated β-lactam resistance in isolates. For cefoxitin DD and BMD results interpreted using / breakpoints, the CA was 97.6% and 96.2%, respectively. There were 4.9% VMEs for cefoxitin DD with 0% MEs, and 3.6% VMEs and 3.9% MEs for cefoxitin BMD. Oxacillin BMD using / breakpoints yielded the highest VMEs at 17.4% and 90% CA. Our findings demonstrate that oxacillin DD tests using the CLSI M100-S28 breakpoints for / and oxacillin BMD and cefoxitin DD tests using the CoNS breakpoints reliably identified -mediated β-lactam resistance in Using PCR as the gold standard, the PBP2a SA culture colony test (Abbott Diagnostics) exhibited 100% sensitivity and specificity whereas 2 false negatives were identified using the PBP2' latex agglutination test kit (Thermo Fisher Scientific) with sensitivity and specificity of 95.8% and 100%, respectively.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Humans; Microbial Sensitivity Tests; Oxacillin; Polymerase Chain Reaction; Sensitivity and Specificity; Staphylococcal Infections; Staphylococcus epidermidis; beta-Lactam Resistance
PubMed: 31462553
DOI: 10.1128/JCM.00961-19 -
Medicine Jan 2023Drug-induced aseptic meningitis (DIAM) is an uncommon meningitis and trimethoprim with or without sulfamethoxazole is the most involved antibiotic. Although DIAM is...
RATIONALE
Drug-induced aseptic meningitis (DIAM) is an uncommon meningitis and trimethoprim with or without sulfamethoxazole is the most involved antibiotic. Although DIAM is easily treated with the discontinuation of the causative drug, the diagnosis is a big challenge for physicians, as it remains a diagnosis of exclusion. Here, we present a case report of trimethoprim-sulfamethoxazole induced aseptic meningitis in a woman with acute osteomyelitis.
PATIENT CONCERNS
A 52-year-old woman was admitted to the hospital for septic shock and acute osteomyelitis of the right homerus. She was started on antibiotic therapy with oxacillin and daptomycin, then oxacillin was replaced with cotrimoxazole, due to its excellent tissue penetration, including bone tissue. During cotrimoxazole therapy, the patient developed a fluent aphasia with ideomotor apraxia and muscle hypertonus.
DIAGNOSIS AND INTERVENTIONS
Having excluded infectious, epileptic and vascular causes of the acute neurologic syndrome of our patient, given the improvement and full recovery after discontinuation of cotrimoxazole, we hypothesized a DIAM.
OUTCOMES
After discontinuation of cotrimoxazole, in 48 hours the patient had a full recovery.
LESSONS
Although DIAM can be easily managed with the withdrawal of the causative drug, it can be difficult to recognize if it is not included in the differential diagnosis. An antimicrobial stewardship program with a strict monitoring of patients by infectious disease specialists is essential, not only to optimize the appropriate use of antimicrobials, but also to improve patient outcomes and reduce the likelihood of adverse events.
Topics: Female; Humans; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Meningitis, Aseptic; Anti-Infective Agents; Anti-Bacterial Agents; Oxacillin
PubMed: 36607874
DOI: 10.1097/MD.0000000000032475 -
The Journal of Antimicrobial... Apr 2021To evaluate the proficiency of microbiology laboratories in Spain in antimicrobial susceptibility testing (AST) of Staphylococcus spp.
OBJECTIVES
To evaluate the proficiency of microbiology laboratories in Spain in antimicrobial susceptibility testing (AST) of Staphylococcus spp.
MATERIALS AND METHODS
Eight Staphylococcus spp. with different resistance mechanisms were selected: six Staphylococcus aureus (CC-01/mecA, CC-02/mecC, CC-03/BORSA, CC-04/MLSBi, CC-06/blaZ and CC-07/linezolid resistant, cfr); one Staphylococcus epidermidis (CC-05/linezolid resistant, 23S rRNA mutation); and one Staphylococcus capitis (CC-08/daptomycin non-susceptible). Fifty-one laboratories were asked to report: (i) AST system used; (ii) antimicrobial MICs; (iii) breakpoints used (CLSI or EUCAST); and (iv) clinical category. Minor, major and very major errors (mEs, MEs and VMEs, respectively) were determined.
RESULTS
The greatest MIC discrepancies found were: (i) by AST method: 19.4% (gradient diffusion); (ii) by antimicrobial agent: daptomycin (21.3%) and oxacillin (20.6%); and (iii) by isolate: CC-07/cfr (48.0%). The greatest error rates were: (i) by AST method: gradient diffusion (4.3% and 5.1% VMEs, using EUCAST and CLSI, respectively); (ii) by breakpoint: 3.8% EUCAST and 2.3% CLSI; (iii) by error type: mEs (0.8% EUCAST and 1.0% CLSI), MEs (1.8% EUCAST and 0.7% CLSI) and VMEs (1.2% EUCAST and 0.6% CLSI); (iii) by antimicrobial agent: VMEs (4.7% linezolid and 4.3% oxacillin using EUCAST); MEs (14.3% fosfomycin, 9.1% tobramycin and 5.7% gentamicin using EUCAST); and mEs (22.6% amikacin using EUCAST).
CONCLUSIONS
Clinical microbiology laboratories should improve their ability to determine the susceptibility of Staphylococcus spp. to some antimicrobial agents to avoid reporting false-susceptible or false-resistant results. The greatest discrepancies and errors were associated with gradient diffusion, EUCAST breakpoints and some antimicrobials (mEs for aminoglycosides; MEs for fosfomycin, aminoglycosides and oxacillin; and VMEs for linezolid and oxacillin).
Topics: Anti-Bacterial Agents; Microbial Sensitivity Tests; Oxacillin; Phenotype; Spain; Staphylococcus
PubMed: 33555012
DOI: 10.1093/jac/dkab017 -
Journal of Biomechanics Jul 2018Delivering charged antibiotics to the intervertebral disc is challenging because of the avascular, negatively charged extracellular matrix (ECM) of the tissue. The...
Delivering charged antibiotics to the intervertebral disc is challenging because of the avascular, negatively charged extracellular matrix (ECM) of the tissue. The purpose of this study was to measure the apparent diffusion coefficient of two clinically relevant, charged antibiotics, vancomycin (positively charged) and oxacillin (negatively charged) in IVD. A one-dimensional steady state diffusion experiment was employed to measure the apparent diffusion coefficient of the two antibiotics in bovine coccygeal annulus fibrosus (AF) tissue. The averaged apparent diffusion coefficient for vancomycin under 20% compressive strain was 7.94 ± 2.00 × 10 m/s (n = 10), while that of oxacillin was 2.26 ± 0.68 × 10 m/s (n = 10). A student's t-test showed that the diffusivity of vancomycin was significantly lower than that of oxacillin. This finding may be attributed to two factors: solute size and possible binding effects. Vancomycin is approximately 3 times larger in molecular weight than oxacillin, meaning that steric hindrance likely plays a role in the slower transport. Reversible binding between positive vancomycin and the negative ECM could also slow down the rate of diffusion. Therefore, more investigation is necessary to determine the specific relationship between net charge on antibiotic and diffusion coefficients in IVD. This study provides essential quantitative information regarding the transport rates of antibiotics in the IVD, which is critical in using computational modeling to design effective strategies to treat disc infection.
Topics: Animals; Annulus Fibrosus; Anti-Bacterial Agents; Cattle; Computer Simulation; Diffusion; Extracellular Matrix; Oxacillin; Vancomycin
PubMed: 29941209
DOI: 10.1016/j.jbiomech.2018.06.008 -
California Medicine Sep 1962The newer penicillins give high promise of overcoming some of the few disadvantages of penicillin-G. THEY FALL INTO THREE GROUPS: The alpha-phenoxy-penicillins; the...
The newer penicillins give high promise of overcoming some of the few disadvantages of penicillin-G. THEY FALL INTO THREE GROUPS: The alpha-phenoxy-penicillins; the penicillinase resistant penicillins; and the penicillins with enhanced activity against gram-negative bacteria. The newer alpha-phenoxy-penicillins offer little over alpha-phenoxy methyl penicillin (penicillin-V). As the length of the side chain is increased, absorption and attainable serum concentration is also increased, but these are questionable benefits and probably not significant for therapeusis. The penicillinase-resistant penicillins have once more brought almost all severe staphylococcal infections within therapeutic range. One of them, methicillin, must be administered parenterally. It is the agent of choice for the treatment of severe, penicillin-G resistant staphylococcal infections, and this is its only clinical indication. Another, oxacillin, which may be administered orally, is partially resistant to gastric acid degradation, but must be given on an empty stomach. It is most useful as prolonged therapy following methicillin, in the treatment of mixed hemolytic streptococcal-penicillin-G resistant staphylococcal infections, and as primary therapy for moderately severe penicillin-G resistant staphylococcal infections. The third group is still mostly in the experimental stage, but some strains of Proteus, E. coli, Salmonella and Shigella are highly vulnerable to their action. Toxic and allergic reactions to the newer penicillins, and crossed allergic reactions with penicillin-G, present unsolved problems.
Topics: Escherichia coli; Methicillin; Oxacillin; Penicillin G; Penicillins; Staphylococcal Infections; Staphylococcus; Streptococcal Infections
PubMed: 13913108
DOI: No ID Found -
Bulletin of the New York Academy of... Jul 1964
Topics: Diagnosis; Endocarditis; Endocarditis, Bacterial; Endocarditis, Subacute Bacterial; Heart Failure; Humans; Intracranial Embolism; Intracranial Embolism and Thrombosis; Methicillin; Mortality; Oxacillin; Penicillins; Ristocetin; Streptomycin; Vancomycin
PubMed: 14150924
DOI: No ID Found -
BioMed Research International 2015The genotypes and oxacillin resistance of 420 S. aureus isolates from pigs (n = 203) and pork (n = 217) were analyzed. Among 18 spa types detected in S. aureus from pig...
The genotypes and oxacillin resistance of 420 S. aureus isolates from pigs (n = 203) and pork (n = 217) were analyzed. Among 18 spa types detected in S. aureus from pig t011, t021, t034, t091, t318, t337, and t1334 were the most frequent. Among 30 spa types found in S. aureus isolates from pork t084, t091, t499, t4309, t12954, and t13074 were dominant. The animal S. aureus isolates were clustered into MLST clonal complexes CC7, CC9, CC15, CC30, and CC398 and meat-derived isolates to CC1, CC7, and CC15. Thirty-six MRSA were isolated exclusively from pigs. All MRSA were classified to spa t011 SCCmecV. BORSA phenotype was found in 14% S. aureus isolates from pigs and 10% isolates from pork meat. spa t034 dominated among BORSA from pigs and t091 among meat-derived BORSA. This is the first report on spa types and oxacillin resistance of S. aureus strains from pigs and pork meat in Poland. Besides S. aureus CC9, CC30, and CC398 known to be distributed in pigs, the occurrence of genotype belonging to CC7 in this species has been reported for the first time. To our knowledge it is also the first report concerning CC398 BORSA isolates from pigs and pork meat.
Topics: Animals; Genetics, Population; Genotype; Meat; Methicillin-Resistant Staphylococcus aureus; Oxacillin; Poland; Staphylococcal Infections; Sus scrofa; Swine
PubMed: 26064878
DOI: 10.1155/2015/141475 -
Journal of Clinical Microbiology Mar 2016Staphylococcus pseudintermedius is a coagulase-positive species that colonizes the nares and anal mucosa of healthy dogs and cats. Human infections with S....
Evaluation of Oxacillin and Cefoxitin Disk and MIC Breakpoints for Prediction of Methicillin Resistance in Human and Veterinary Isolates of Staphylococcus intermedius Group.
Staphylococcus pseudintermedius is a coagulase-positive species that colonizes the nares and anal mucosa of healthy dogs and cats. Human infections with S. pseudintermedius range in severity from bite wounds and rhinosinusitis to endocarditis; historically, these infections were thought to be uncommon, but new laboratory methods suggest that their true incidence is underreported. Oxacillin and cefoxitin disk and MIC tests were evaluated for the detection of mecA- or mecC-mediated methicillin resistance in 115 human and animal isolates of the Staphylococcus intermedius group (SIG), including 111 Staphylococcus pseudintermediusand 4 Staphylococcus delphini isolates, 37 of which were mecA positive. The disk and MIC breakpoints evaluated included the Clinical and Laboratory Standards Institute (CLSI) M100-S25 Staphylococcus aureus/Staphylococcus lugdunensis oxacillin MIC breakpoints and cefoxitin disk and MIC breakpoints, the CLSI M100-S25 coagulase-negative Staphylococcus (CoNS) oxacillin MIC breakpoint and cefoxitin disk breakpoint, the CLSI VET01-S2 S. pseudintermedius oxacillin MIC and disk breakpoints, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) S. pseudintermedius cefoxitin disk breakpoint. The oxacillin results interpreted by the VET01-S2 (disk and MIC) and M100-S25 CoNS (MIC) breakpoints agreed with the results of mecA/mecC PCR for all isolates, with the exception of one false-resistant result (1.3% of mecA/mecC PCR-negative isolates). In contrast, cefoxitin tests performed poorly, ranging from 3 to 89% false susceptibility (very major errors) and 0 to 48% false resistance (major errors). BD Phoenix, bioMérieux Vitek 2, and Beckman Coulter MicroScan commercial automated susceptibility test panel oxacillin MIC results were also evaluated and demonstrated >95% categorical agreement with mecA/mecC PCR results if interpreted by using the M100-S25 CoNS breakpoint. The Alere penicillin-binding protein 2a test accurately detected all mecA-positive isolates, although for four isolates, cefoxitin induction was required prior to testing. These data demonstrate that the cefoxitin surrogate test does not reliably detect the presence of mecA in S. pseudintermedius isolates and that laboratories should perform oxacillin disk or MIC tests of these isolates when they are encountered.
Topics: Animals; Cefoxitin; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Oxacillin; Staphylococcal Infections; Staphylococcus intermedius
PubMed: 26607988
DOI: 10.1128/JCM.02864-15 -
Journal of Clinical Microbiology Apr 2023Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin...
Retrospective Evaluation of the Association of Oxacillin MIC on Acute Treatment Outcomes with Cefazolin and Antistaphylococcal Penicillins in Methicillin-Susceptible Staphylococcus aureus Bacteremia.
Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 μg/mL compared to strains with MIC of oxacillin < 1 μg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 μg/mL and 176 isolates with an MIC < 1 μg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL (16.4% versus 15.9%, = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, = 0.86) or cefazolin (10.3% versus 11.9%, = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 μg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.
Topics: Oxacillin; Cefazolin; Methicillin-Resistant Staphylococcus aureus; Bacteremia; Staphylococcal Infections; Anti-Bacterial Agents; Humans; Male; Female; Middle Aged; Aged; Treatment Outcome; Retrospective Studies
PubMed: 36988505
DOI: 10.1128/jcm.00039-23