-
Journal of Clinical Microbiology Feb 2018is a beta-hemolytic, coagulase-variable colonizer of small animals that can cause opportunistic infections in humans. In veterinary isolates, the rate of -mediated... (Comparative Study)
Comparative Study
Evaluation of Oxacillin and Cefoxitin Disk Diffusion and MIC Breakpoints Established by the Clinical and Laboratory Standards Institute for Detection of -Mediated Oxacillin Resistance in Staphylococcus schleiferi.
is a beta-hemolytic, coagulase-variable colonizer of small animals that can cause opportunistic infections in humans. In veterinary isolates, the rate of -mediated oxacillin resistance is significant, with reported resistance rates of >39%. The goal of this study was to evaluate oxacillin and cefoxitin disk diffusion (DD) and MIC breakpoints for detection of -mediated oxacillin resistance in 52 human and 38 veterinary isolates of Isolates were tested on multiple brands of commercial media and according to Clinical and Laboratory Standards Institute (CLSI) methods. Zone diameters and MIC values were interpreted using CLSI breakpoints (CLSI, , 2017) for /, coagulase-negative staphylococci (CoNS), and Results were compared to those of PCR. Twenty-nine of 90 (32%) isolates were positive. Oxacillin inhibition zone sizes and MICs interpreted by breakpoints reliably differentiated -positive and -negative isolates, with a categorical agreement (CA) of 100% and no very major errors (VMEs) or major errors (MEs) for all media. For cefoxitin DD results interpreted using / and CoNS breakpoints, CA values were 85% and 75%, respectively, and there were 72% and 64% VMEs, respectively, and 0 MEs. For cefoxitin MICs interpreted using breakpoints, CA was 81%, and there were 60% VMEs and no MEs. Our data demonstrate that oxacillin DD or MIC testing methods using the current breakpoints reliably identify -mediated oxacillin resistance in , while cefoxitin DD and MIC testing methods perform poorly.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Oxacillin; Penicillin-Binding Proteins; Polymerase Chain Reaction; Staphylococcal Infections; Staphylococcus
PubMed: 29187565
DOI: 10.1128/JCM.01653-17 -
Journal of Microbiology, Immunology,... Apr 2022Staphylococcus lugdunensis is a Gram-positive coagulase-negative bacterium and is recognized as a critical pathogenic species recently. Here, we aimed to evaluate the...
BACKGROUND/PURPOSE
Staphylococcus lugdunensis is a Gram-positive coagulase-negative bacterium and is recognized as a critical pathogenic species recently. Here, we aimed to evaluate the cefoxitin disk diffusion (CDD), oxacillin agar dilution (OAD), and mecA PCR for detecting oxacillin-resistant S. lugdunensis (ORSL) isolates.
METHODS
Multilocus sequence typing (MLST) analysis was performed to determine the clonality of 117 S. lugdunensis isolates isolated between May 2009 and Jul 2014. CDD, OAD, and mecA PCR were used to identify oxacillin-resistant S. lugdunensis (ORSL).
RESULTS
MLST results showed that the most common sequence type (ST) of our S. lugdunensis isolates was ST6 (35.9%) followed by ST3 (28.2%), ST27 (17.9%), and ST4 (6.8%). CDD and OAD showed that 39 and 43 isolates were ORSL, respectively. 4 ST3 CDD-susceptible S. lugdunensis (OSSL) isolates had MIC values ≥ 4 for oxacillin. mecA PCR results showed that 43 OAD-resistant S. lugdunensis and 3 OAD-susceptible ST27 S. lugdunensis had the mecA gene. Therefore, OAD was used as the gold standard to evaluate the performance of CDD and mecA PCR for identifying ORSL. The overall sensitivity, specificity, and accuracy of CCD for ORSL detection was 90.7%, 100%, and 96.8%, respectively. The sensitivity, specificity, and accuracy of mecA PCR for identifying ORSL was 100%, 95.9%, and 97.44%, respectively.
CONCLUSION
Our results indicate that OAD shows higher accuracy for ORSL detection compared with CDD and mecA PCR.
Topics: Agar; Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Oxacillin; Staphylococcal Infections; Staphylococcus lugdunensis
PubMed: 33836942
DOI: 10.1016/j.jmii.2021.02.009 -
The American Journal of Case Reports Mar 2019BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic life-threatening reaction comprised of fevers, rash, and leukocytosis with...
BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic life-threatening reaction comprised of fevers, rash, and leukocytosis with eosinophilia. Though characteristically associated with leukocytosis, there are rare case reports of DRESS-induced agranulocytosis. DRESS is most frequently caused by antiepileptic medications; however, it has very rarely been reported in relation to oxacillin. We describe a case of oxacillin-induced DRESS associated with agranulocytosis. CASE REPORT A 52-year-old male was admitted for an epidural abscess secondary to oxacillin-sensitive Staphylococcus aureus, for which an extended course of oxacillin and rifampin was initiated. On day 22 of therapy, the patient developed a fever of 38.7°C (101.6°F) with rigors. His complete blood cell count revealed new leukopenia (1.8×10³/uL) with 16% eosinophils and 3% atypical lymphocytes. Antibiotics were transitioned from oxacillin and rifampin to vancomycin, cefepime, and rifampin for presumed sepsis of unclear etiology. On day 23, he was noted to have a pruritic erythematous blanching papular rash on his chest, trunk, neck, and left upper extremity. Infectious workup was unrevealing, and his fever curve up-trended to 39.3°C (102.7°F) with no clinical improvement on broad-spectrum antimicrobials, suggestive of a non-infectious etiology of his rash and fevers. His rash evolved into confluent red patches, and eosinophilia rose to 21%, which was concerning for a drug reaction. His RegiSCAR score was calculated to be 6, consistent with definite DRESS. Leukopenia resolved (6.3×10³/uL) 4 days after discontinuing oxacillin. His epidural abscess was ultimately treated with daptomycin, and DRESS was managed supportively with antihistamines and triamcinolone cream. CONCLUSIONS We highlight this case because of the rarity of DRESS with agranulocytosis related to oxacillin. Beta-lactam antibiotics are widely used, and while DRESS is an uncommon condition, clinicians should consider this diagnosis when managing patients with fevers, leukopenia, and rash.
Topics: Anti-Bacterial Agents; Drug Hypersensitivity Syndrome; Humans; Male; Middle Aged; Oxacillin; Staphylococcal Infections
PubMed: 30877266
DOI: 10.12659/AJCR.913748 -
Microbiology Spectrum Apr 2022Staphylococcus aureus poses a significant threat to human health due to its virulence and multidrug resistance. In addition, recalcitrant biofilm formation of S. aureus...
Staphylococcus aureus poses a significant threat to human health due to its virulence and multidrug resistance. In addition, recalcitrant biofilm formation of S. aureus often results in chronic infection and the treatment tolerance toward the traditional antibiotics. Thus, the development of novel antimicrobial agents capable to inhibit or eradicate S. aureus biofilm formation does matter. Here, we demonstrated that clemastine showed slight bacteriostatic activity and enhanced the antibacterial activity of oxacillin against S. aureus. Moreover, the dramatic inhibition of biofilm formation was found in clinical S. aureus strains by clemastine. Clemastine inhibited the release of eDNA during the biofilm formation and decreased the S. aureus hemolytic activity. Moreover, the S. aureus SA113 treated with clemastine displayed the decreased transcriptional level of the biofilm formation relevant genes (, , and ), virulence genes (, , , and ), and the regulatory genes . The proteomics analysis of SA113 treated with clemastine demonstrated the significant changes in levels of biofilm-related proteins (stress response regulators ClpB and GroS, ATP-binding proteins, and urease metabolism), virulence-related proteins (SspA, superantigen, and VWbp), and methicillin resistance-related proteins (glutamine metabolism). The genetic mutations on (cyclic di-AMP phosphodiesterase) were found in the clemastine-induced tolerant derivative isolate by whole-genome sequencing. Furthermore, the interaction between clemastine and GdpP protein was demonstrated by the molecular docking, overexpression experiment, and thermal stability assay. Conclusively, clemastine might exert its inhibitory effects against the biofilm formation and hemolysis in S. aureus through targeting GdpP protein. The biofilm formation, which protects bacteria from stresses, including antibiotics and host immune responses, can be commonly found in clinical S. aureus isolates worldwide. Treatment failure of traditional antibiotics in biofilm-associated S. aureus infections remains a serious challenge. The novel anti-biofilm drug is urgently needed to address the looming crisis. In this study, clemastine, which is a histamine receptor H1 (HRH1) antagonist, was found to have a novel role of the significant inhibition against the biofilm formation and hemolytic activity of S. aureus and enhanced antibacterial activity against S. aureus when used in combination with oxacillin by targeting the GdpP protein. The discovery of this study identified novel use and mechanism of action of clemastine as a potential anti-biofilm drug for clinical application for S. aureus infectious.
Topics: Anti-Bacterial Agents; Biofilms; Clemastine; Hemolysis; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Docking Simulation; Oxacillin; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35234502
DOI: 10.1128/spectrum.00541-21 -
BMC Microbiology Jul 2016The emergence and spread of multidrug resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA) has serious health consequences in the presence of sub-MIC...
BACKGROUND
The emergence and spread of multidrug resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA) has serious health consequences in the presence of sub-MIC antibiotics. Therefore, this study was designed to evaluate β-lactamase activity, efflux activity, biofilm formation, and gene expression pattern in Staphylococcus aureus KACC 10778, S. aureus ATCC 15564, and S. aureus CCARM 3080 exposed to sublethal concentrations of levofloxacin and oxacillin.
RESULTS
The decreased MICs were observed in S. aureus KACC and S. aureus ATCC when exposed to levofloxacin and oxacillin, while and S. aureus CCARM remained resistance to streptomycin (512 μg/mL) in the presence of levofloxacin and imipenem (>512 μg/mL) in the presence of oxacillin. The considerable increase in extracellular and membrane-bound β-lactamase activities was observed in S. aureus ATCC exposed to oxacillin (>26 μmol/min/mL). The antibiotic susceptibility of all strains exposed to EPIs (CCCP and PAβN) varied depending on the classes of antibiotics. The relative expression levels of adhesion-related genes (clfA, clfB, fnbA, fnnB, and icaD), efflux-related genes (norB, norC, and qacA/B), and enterotoxin gene (sec) were increased more than 5-fold in S. aureus CCARM. The eno and qacA/B genes were highly overexpressed by more than 12- and 9-folds, respectively, in S. aureus CCARM exposed to levofloxacin. The antibiotic susceptibility, lactamase activity, biofilm-forming ability, efflux activity, and gene expression pattern varied with the intrinsic antibiotic resistance of S. aureus KACC, S. aureus ATCC, and S. aureus CCARM exposed to levofloxacin and oxacillin.
CONCLUSIONS
This study would provide useful information for better understating of combination therapy related to antibiotic resistance mechanisms and open the door for designing effective antibiotic treatment protocols to prevent excessive use of antibiotics in clinical practice.
Topics: Adhesins, Bacterial; Bacterial Adhesion; Bacterial Proteins; Biofilms; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Coagulase; Dipeptides; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genotype; Imipenem; Levofloxacin; Membrane Transport Proteins; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxacillin; Phenotype; Polymerase Chain Reaction; Staphylococcus aureus; Streptomycin; beta-Lactamases
PubMed: 27473500
DOI: 10.1186/s12866-016-0791-7 -
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 -
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 -
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 -
Journal of Global Antimicrobial... Mar 2020This study evaluated disc diffusion tests and agar screening for detecting mecA-mediated oxacillin resistance in Staphylococcus lugdunensis (S. lugdunensis). (Comparative Study)
Comparative Study
Evaluation of disc diffusion tests and agar screening for predicting mecA-mediated oxacillin resistance in Staphylococcus lugdunensis revealed a cefoxitin-susceptible, mecA-positive S. lugdunensis clonal complex 27 clone.
OBJECTIVES
This study evaluated disc diffusion tests and agar screening for detecting mecA-mediated oxacillin resistance in Staphylococcus lugdunensis (S. lugdunensis).
METHODS
Staphylococcus lugdunensis isolates (n = 179) from diverse sources in Hong Kong during 1998-2018 were investigated by disc diffusion tests (cefoxitin and oxacillin) and inoculation onto oxacillin (1 μg/mL and 2 μg/mL) and chromID methicillin-resistant Staphylococcus aureus (MRSA) agars. The results were compared with mecA PCR as the reference. Isolates with discordant results were further tested by MIC and penicillin-binding protein 2a (PBP2a) assays.
RESULTS
Cefoxitin and oxacillin zone diameters were not distributed in ways that allowed reliable division of the mecA-positive (n = 52) and mecA-negative (n = 127) isolates. On applying the 2019 Clinical Laboratory Standards Institute (CLSI) M100 breakpoints for cefoxitin disc results, there was 88% categorical agreement (CA) and 40% very major error (VME). Screening using 2 μg/mL oxacillin agar reliably differentiated mecA-positive and mecA-negative isolates (100% CA) without any major error (ME) or VME results. The performance of screening using 1 μg/mL oxacillin agar or ChromID MRSA agar was variable (74-89% CA, 0-38% ME and 0-37% VME). The mecA-positive isolates (n = 21) that could not be detected by the cefoxitin disc test were further characterised. The cefoxitin MIC for all 21 isolates was ≤4 μg/mL. Twenty isolates had an oxacillin MIC of 1-2 μg/mL and one had an oxacillin MIC of 4 μg/mL. All had positive PBP2a results and were typed as clonal cluster 27/SCCmec V.
CONCLUSIONS
These findings highlight the need to evaluate phenotypic methods using mecA-positive S. lugdunensis with different oxacillin resistance phenotypes.
Topics: Agar; Bacterial Load; Bacterial Proteins; Carrier State; Cefoxitin; Disk Diffusion Antimicrobial Tests; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Oxacillin; Phenotype; Staphylococcal Infections; Staphylococcus lugdunensis
PubMed: 31493529
DOI: 10.1016/j.jgar.2019.08.021 -
Proceedings of the National Academy of... Jul 2022Human infections with methicillin-resistant (MRSA) are commonly treated with vancomycin, and strains with decreased susceptibility, designated as...
Human infections with methicillin-resistant (MRSA) are commonly treated with vancomycin, and strains with decreased susceptibility, designated as vancomycin-intermediate (VISA), are associated with treatment failure. Here, we profiled the phenotypic, mutational, and transcriptional landscape of 10 VISA strains adapted by laboratory evolution from one common MRSA ancestor, the USA300 strain JE2. Using functional and independent component analysis, we found that: 1) despite the common genetic background and environmental conditions, the mutational landscape diverged between evolved strains and included mutations previously associated with vancomycin resistance (in , , , , and ) as well as novel adaptive mutations (SAUSA300_RS04225, , , and ); 2) the first wave of mutations affected transcriptional regulators and the second affected genes involved in membrane biosynthesis; 3) expression profiles were predominantly strain-specific except for and , which were the only two genes significantly differentially expressed in all clones; 4) three independent virulence systems (φSa3, SaeR, and T7SS) featured as the most transcriptionally perturbed gene sets across clones; 5) there was a striking variation in oxacillin susceptibility across the evolved lineages (from a 10-fold increase to a 63-fold decrease) that also arose in clinical MRSA isolates exposed to vancomycin and correlated with susceptibility to teichoic acid inhibitors; and 6) constitutive expression of the VraR regulon explained cross-susceptibility, while mutations in were associated with cross-resistance. Our results show that adaptation to vancomycin involves a surprising breadth of mutational and transcriptional pathways that affect antibiotic susceptibility and possibly the clinical outcome of infections.
Topics: Anti-Bacterial Agents; Evolution, Molecular; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxacillin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Vancomycin Resistance; Virulence
PubMed: 35858453
DOI: 10.1073/pnas.2118262119