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Journal of General and Family Medicine Sep 2019An 88-year-old woman with a history of meningioma and dementia was admitted with high fever, loss of appetite, and nausea in July. Urinary tract infection was suspected....
An 88-year-old woman with a history of meningioma and dementia was admitted with high fever, loss of appetite, and nausea in July. Urinary tract infection was suspected. Computed tomography (CT) showed no significant findings. Urinary findings improved with administration of ceftriaxone. However, high fever appeared on hospital day 28, and CT identified a gallbladder stone without any abdominal symptoms. We considered the possibility of ceftriaxone-associated pseudolithiasis and changed pharmacotherapy to cefmetazole. CT on day 34 showed a reduction in the size of the gallbladder stone. Ceftriaxone-associated pseudolithiasis might arise in the absence of abdominal symptoms, and clinicians should take the patient background and season into account when using this agent.
PubMed: 31516810
DOI: 10.1002/jgf2.269 -
Antibiotics (Basel, Switzerland) Mar 2022The optimal regimens of cefmetazole and flomoxef for the treatment of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales...
Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing in Patients with Invasive Urinary Tract Infection Considering Renal Function.
The optimal regimens of cefmetazole and flomoxef for the treatment of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are not well defined. Our study found that the pharmacokinetic/pharmacodynamic targets for cefmetazole and flomoxef were 70% T > MIC, which is suggestive of bactericidal activity. A Monte Carlo simulation (MCS) was performed using the published data to calculate a new probability of target attainment (PTA ≥ 90%) for each renal function. The MCS was performed with 1000 replicates, and clinical breakpoints were calculated to attain PTA ≥ 90% for creatinine clearance (CCR) of 10, 30, 50, and 70 mL/min. The 90% ≥ PTA (70% T > MIC) of cefmetazole and flomoxef in patients who received a standard regimen (0.5 or 1 g, 1 h injection) for each renal function was calculated. Our results suggest that in patients with CCR of less than 30, 31−59, and more than 60 mL/min, the optimal dosage of cefmetazole would be 1 g q12 h, 1 g q8 h, and 1 g q6 h, respectively. Furthermore, in patients with CCR of less than 10, 10−50, and more than 50 mL/min, the optimal dosage of flomoxef would be 1 g q24 h, 1 g q8 h or 12 h, and 1 g q6 h, respectively.
PubMed: 35453208
DOI: 10.3390/antibiotics11040456 -
Antimicrobial Agents and Chemotherapy Oct 2023Cefmetazole is active against extended-spectrum β-lactamase-producing (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter,... (Observational Study)
Observational Study
Cefmetazole is active against extended-spectrum β-lactamase-producing (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups ( = 0.54, = 0.10, and = 0.79, respectively). In all cases with available data (cefmetazole : = 61, meropenem : = 22), both drugs were microbiologically effective. In all isolates, was detected as the extended-spectrum β-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.
Topics: Humans; Cefmetazole; Meropenem; beta-Lactamases; Escherichia coli; Urinary Tract Infections; Escherichia coli Infections; Anti-Bacterial Agents
PubMed: 37702483
DOI: 10.1128/aac.00510-23 -
Journal of Thoracic Disease Feb 2022Reduning (RDN) is a common Chinese medicine preparation with antibacterial, anti-inflammatory, antiviral and immunomodulatory effects in respiratory infectious diseases....
BACKGROUND
Reduning (RDN) is a common Chinese medicine preparation with antibacterial, anti-inflammatory, antiviral and immunomodulatory effects in respiratory infectious diseases. Clinically, it is used in combination with antibiotics, but its synergistic effect and mechanism in treating severe pneumonia remain unclear.
METHODS
A rat model of severe pneumonia and an coculture model consisting of A549 and THP-1 cells were used to observe the synergistic effect of RDN on severe pneumonia. The inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA). The localization of Aryl hydrocarbon receptor (AhR) in A549 cells was observed by immunofluorescence, and the interaction of AhR and signal transducer and activator of transcription 3 (STAT3) proteins was observed by co-immunoprecipitation. AhR-Src tyrosine kinase (Src)-STAT3 pathway in rats and A549 cells were examined by Western Blot. Histopathological changes were observed by Hematoxylin-eosin (HE) staining, X-ray and survival rates were used to evaluate the effects of paclitaxel on severe pneumonia rats.
RESULTS
RDN regulation of Src-STAT3-interleukin 10 (IL-10) signaling pathway activation and macrophage polarization were mediated through the nuclear receptor AhR. The expression of AhR was significantly increased after RDN treatment, and this effect was accompanied by STAT3 expression increasing. Coimmunoprecipitation confirmed an interaction between AhR and STAT3 and upregulated IL-10 expression. Silencing AhR decreased Src, STAT3, and IL-10 expression. RDN activated AhR and increased Src, STAT3, and IL-10 expression. In addition, RDN regulated the polarization of macrophages RDN combined with cefmetazole sodium significantly reduced the pulmonary bacterial load, alleviated lung injury, and reduced o inflammatory factors expression, improving their survival.
CONCLUSIONS
RDN can synergistically enhance the effect of cefmetazole sodium treatment in severe pneumonia, and the mechanism may involve increasing the expression level of IL-10 mediated through the AhR-Src-STAT3 pathway, driving the polarization of macrophages, and attenuating the cytokine storm to control inflammation in severe pneumonia.
PubMed: 35280469
DOI: 10.21037/jtd-22-126 -
Antimicrobial Agents and Chemotherapy Sep 2015The efficacy of cefmetazole and flomoxef (CF) for the treatment of patients with extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) bacteremia (ESBL-CF...
The efficacy of cefmetazole and flomoxef (CF) for the treatment of patients with extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) bacteremia (ESBL-CF group) was compared with that of carbapenem treatment for ESBL-EC patients (ESBL-carbapenem group) and with that of CF treatment in patients with non-ESBL-EC bacteremia (non-ESBL-CF group). Adult patients treated for E. coli bacteremia in four hospitals were retrospectively evaluated. The 30-day mortality rates in patients belonging to the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were compared as 2 (empirical and definitive therapy) cohorts. The adjusted hazard ratios (aHRs) for mortality were calculated using Cox regression models with weighting according to the inverse probability of propensity scores for receiving CF or carbapenem treatment. The empirical-therapy cohort included 104 patients (ESBL-CF, 26; ESBL-carbapenem, 45; non-ESBL-CF, 33), and the definitive-therapy cohort included 133 patients (ESBL-CF, 59; ESBL-carbapenem, 54; non-ESBL-CF, 20). The crude 30-day mortality rates for patients in the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were, respectively, 7.7%, 8.9%, and 3.0% in the empirical-therapy cohort and 5.1%, 9.3%, and 5.0% in the definitve-therapy cohort. In patients without hematological malignancy and neutropenia, CF treatment for ESBL-EC patients was not associated with mortality compared with carbapenem treatment (empirical-therapy cohort: aHR, 0.87; 95% confidence interval [CI], 0.11 to 6.52; definitive therapy cohort: aHR, 1.04; CI, 0.24 to 4.49). CF therapy may represent an effective alternative to carbapenem treatment for patients with ESBL-EC bacteremia for empirical and definitive therapy in adult patients who do not have hematological malignancy and neutropenia.
Topics: Aged; Bacteremia; Cefmetazole; Cephalosporins; Escherichia coli; Female; Humans; Male; Middle Aged; beta-Lactamases
PubMed: 26100708
DOI: 10.1128/AAC.00701-15 -
Surgery Apr 2022During surgery, the effectiveness of perioperative prophylactic antibiotic administration against surgical site infections is inferred from serum concentrations and not...
BACKGROUND
During surgery, the effectiveness of perioperative prophylactic antibiotic administration against surgical site infections is inferred from serum concentrations and not from tissues where local infections occur. This study aimed to measure the serum and tissue concentrations of cefmetazole in colorectal surgery cases to clarify whether there is an association between the incidence of surgical site infections and antibiotic concentrations.
METHODS
This prospective cohort study was performed at a single tertiary care center. The data of 105 patients who underwent colorectal surgery between October 2017 and September 2019 were evaluated. The primary outcome was the incidence of surgical site infections. Univariate analysis was performed to investigate the association between surgical site infections, perioperative factors, and the serum and tissue concentrations of cefmetazole.
RESULTS
The incidence of surgical site infections was 13/105 (12.4%). Cefmetazole concentrations were measured at initial incision (serum; 101 vs 93.1 mg/L, P = .75, subcutaneous fat tissue; 2.8 vs 3.7 mg/g, P = .15), intestinal resection (serum; 35.1 vs 36.7 mg/L, P = .63, mesenteric adipose tissue; 1.3 vs 1.7 mg/g, P = .55), and at skin closure (serum; 34.5 vs 44.8 mg/L, P = .18, subcutaneous fat tissue; 1.0 vs 2.2 mg/g, P = .09). In univariate analysis with P ≤ .10, cefmetazole concentration in subcutaneous fat tissue at skin closure was found to be a significant risk factor for surgical site infections. Age, additional intraoperative administration of cefmetazole, and creatinine clearance were also significant risk factors for the occurrence of surgical site infections.
CONCLUSION
Low subcutaneous fat cefmetazole concentrations at skin closure during gastrointestinal operations may also be involved in the occurrence of surgical site infections.
Topics: Adipose Tissue; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cefmetazole; Digestive System Surgical Procedures; Humans; Prospective Studies; Surgical Wound Infection
PubMed: 34772516
DOI: 10.1016/j.surg.2021.10.013 -
Journal of Global Antimicrobial... Jun 2022To explore the genomic characterization of an IMP-8-producing Ochrobactrum anthropic and give suggestions for the application of antibiotics.
OBEJECTIVES
To explore the genomic characterization of an IMP-8-producing Ochrobactrum anthropic and give suggestions for the application of antibiotics.
METHODS
In 2021, the infection caused by CRKP was under control after nearly three months of using CAV, however, carbapenem-resistant O. anthropi isolates were collected from a rectal swab sample of a patient with Lumbar Disc Herniation Postoperative Infection. The rectal swab was then enriched in lysogeny broth overnight and inoculated onto China Blue agar plates containing 0.3µg/mL meropenem. And we investigated the characteristics of this carbapenem-resistant O. anthropi by MALDI-TOF MS, Immune colloidal gold technique, conjugation experiment, whole genome sequencing and antimicrobial susceptibility testing.
RESULTS
Antimicrobial susceptibility testing showed that the O. anthropi were resistant to imipenem, cefmetazole, ceftazidime, cefotaxime, piperacillin/tazobactam, sulbactam/cefopcrazone, ceftazidime/avibactam, cefepime, ciprofloxacin, aztreonam, and not susceptible to meropenem, ertapenem, polymyxin B, tigecycline, amikacin. Immune colloidal gold technique reflected that this strain produced IMP carbapenemases, and the presence of IMP-8 was verified by WGS, which was located in a 21,442 bp, nonconjugative plasmid.
CONCLUSION
Improper antibiotic treatment can cause intestinal flora imbalance and even bacteremia in patients, we should use antibiotics wisely and develop individualized treatment options.
Topics: Anti-Bacterial Agents; Carbapenems; Ceftazidime; Gold Colloid; Humans; Meropenem; Microbial Sensitivity Tests; Ochrobactrum anthropi; beta-Lactamases
PubMed: 35346886
DOI: 10.1016/j.jgar.2022.03.016 -
International Journal of Environmental... Oct 2019Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events;... (Meta-Analysis)
Meta-Analysis
Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events; however, a comprehensive evaluation regarding the association is lacking. A systematic review and meta-analysis were conducted to assess the safety profile of NMTT-cephalosporins with respect to hypoprothrombinemia and bleeding. The MEDLINE, Embase, Cochrane, and RISS databases were systematically searched for clinical studies up to October 2018. The association between NMTT-cephalosporins and hypoprothrombinemia was estimated using an odds ratio (OR) with a 95% confidence interval (CI). A total of 15 studies on cefamandole, cefoperazone, cefotetan, cefmetazole, and moxalactam were identified and included in the meta-analysis. Hypoprothrombinemia (OR 1.676, 95% CI 1.275-2.203) and prothrombin time (PT) prolongation (OR 2.050, 95% CI 1.398-3.005) were significantly associated with NMTT-cephalosporins, whereas bleeding was not (OR 1.359, 95% CI 0.920-2.009). Subgroup analyses revealed that cefoperazone (OR 2.506, 95% CI 1.293-4.860), cefamandole (OR 3.247, 95% CI 1.083-9.733), and moxalactam (OR 3.367, 95% CI 1.725-6.572) were significantly associated with hypoprothrombinemia. An Antimicrobial Stewardship Program led by a multidisciplinary team could play a critical role in monitoring cephalosporin-related hypoprothrombinemia or PT prolongation in patients with underlying clinical conditions at risk for bleeding. The multidisciplinary team could also assist in communicating the potential safety concerns regarding NMTT-cephalosporin use with healthcare professionals to decrease the risk of adverse events.
Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Hypoprothrombinemias; Male
PubMed: 31623191
DOI: 10.3390/ijerph16203937 -
Infection and Drug Resistance 2022Cefmetazole (CMZ), a cephamycin antibiotic, is primarily used as a definitive therapy for Extended Spectrum β-Lactamase (ESBL)-producing infections. However, the...
PURPOSE
Cefmetazole (CMZ), a cephamycin antibiotic, is primarily used as a definitive therapy for Extended Spectrum β-Lactamase (ESBL)-producing infections. However, the mechanism of CMZ resistance in is still unknown. To elucidate the resistance mechanism and to determine combined drugs for prevention of resistance acquisition.
METHODS
Clinical isolates of 14 ESBL-producing and non-producing 12 isolates were used in in vitro testing of CMZ resistance acquisition. After 10-day of CMZ exposure (1st subculture), these strains were incubated in an antibacterial-free medium for 14-day. These strains were again exposed to CMZ for 10-day (2nd subculture) and confirmed for changes in MIC. For each strain detected after 1st subculture, each mRNA expression level of porin, chromosomal , and drug-efflux pump was measured using real-time RT-PCR. Relebactam (REL) has the potency to recover antimicrobial activity against carbapenem-resistant that has porin deficiency. REL was added to the CMZ dilution series, and MIC changes and those of porin were confirmed.
RESULTS
Of these 26 strains, 15 strains (57.7%) acquired resistance after 1st subculture, but after passage culture on the antibacterial-free medium, 11 strains recovered susceptibility. These 11 strains showed resistance after 2nd subculture. The expression levels of and were significantly decreased in these strains (<0.05). When REL was added, all strains suppressed resistance acquisition after 1st subculture. The mechanism was the activation of .
CONCLUSION
Our results showed that the mRNA expression levels of genes encoding porin were decreased in the strains that acquired resistance due to CMZ exposure, and that and in particular were thought to be involved in the acquisition of resistance. The CMZ acquisition of resistance was also suppressed by the concomitant use of REL and actually suppressed the decrease in mRNA expression in . It was confirmed that porin reactivated by REL.
PubMed: 36237294
DOI: 10.2147/IDR.S382142 -
Frontiers in Microbiology 2021We aimed to optimize and validate the drug susceptibility test (DST) assay by SYBR Green I/PI (SG-PI) method using a panel of 89 clinical isolates in comparison with...
BACKGROUND
We aimed to optimize and validate the drug susceptibility test (DST) assay by SYBR Green I/PI (SG-PI) method using a panel of 89 clinical isolates in comparison with the conventional DST method to three most important antibiotics used for treatment of this bacterial infection, including imipenem, cefmetazole, and gentamicin.
METHODS
By staining with SYBR Green I and PI dyes, green fluorescence and red fluorescence, which linearly correlated with the percentages of live and dead or membrane damaged cells, respectively, were used to produce two standard curves to calculate the relative cell membrane impermeable rates for each log and stationary phase cultures. Stationary phase cells were used in imipenem and cefmetazole SG-PI DST assay whereas log phase cells were used in the gentamicin assay. The conventional broth microdilution method was used as a gold standard for DST for comparison.
RESULTS
Data showed that after antibiotic treatment for 30-60 min, the antibiotic-resistant strains had significantly higher numbers of surviving cells than the susceptible strains at different concentrations of imipenem, cefmetazole, and gentamicin, where the average relative membrane impermeable rates were 88.5, 92.5, and 103.8% for resistant clinical strains, respectively, and 9.1, 49.3, and 71.5% for susceptible strains, respectively. Overall, the total concordances between the ultra-rapid SG-PI method and conventional minimal inhibitory concentration assay in diagnosing imipenem, cefmetazole and gentamicin resistance were high and were 96.6% (86/89), 95.4% (83/87), and 95.5% (85/89), respectively.
CONCLUSION
We demonstrate that our novel SG-PI assay can accurately and stably detect resistance to different antibiotics in clinical isolates of in an ultra-fast manner in 60-90 min.
PubMed: 34512572
DOI: 10.3389/fmicb.2021.694522