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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 -
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 -
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 -
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 Mar 1989Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and cefmetazole with probenecid pretreatment. Single 2-g doses of cefmetazole sodium and cefoxitin sodium were given intravenously as a 5-min infusion. Concentrations of cefmetazole and cefoxitin were determined by using a specific semiautomated high-performance liquid chromatographic method. Concentration-time profiles of cefmetazole and cefoxitin declined in a biexponential manner from peak levels. Compared with cefoxitin, cefmetazole had a significantly (P less than 0.05) higher mean (+/- standard error of the mean) peak concentration in serum (290 +/- 11 versus 244 +/- 10 micrograms/ml), a longer terminal disposition half-life (1.50 +/- 0.14 versus 0.81 +/- 0.04 h), lower systemic clearance (111.7 +/- 4.7 versus 279 +/- 12 ml/min) and renal clearance (78.7 +/- 4.3 versus 221 +/- 14 ml/min) of intact drug, and a slightly smaller steady-state volume of distribution (10.3 +/- 0.21 versus 12.8 +/- 0.48 liters). Mean recoveries of cefmetazole and cefoxitin in urine were approximately 71 and 77%, respectively. Pretreatment of volunteers with probenecid (1 g orally) significantly (P less than 0.05) increased concentrations of cefmetazole in serum 1 h after drug administration without significantly increasing maximum concentrations in serum. Mean areas under the concentration-time curve (466 +/- 27 versus 295 +/- 13 micrograms.h/ml) and terminal disposition half-lives (2.27 +/- 0.13 versus 1.50 +/- 0.14 h) of cefmetazole increased. Systemic clearance (72.1 +/- 4.0 versus 111.7 +/- 4.7 ml/min) and renal clearance (47.4 +/- 4.0 versus 78.7 +/- 4.3 ml/min) of intact antibiotic decreased. Mean recoveries (65.9 +/- 3.7 versus 71.0 +/- 3.2%) of intact cefmetazole in urine were not significantly (P > 0.05) different. Elimination of cefmetazole in urine was also significantly prolonged by probenecid, with substantial concentrations of cefmetazole (>/= 20 micrograms/ml) found in the 12- to 24-h urine collection for 14 to 16 volunteers. The results show that cefmetazole remains at clinically relevant concentrations (1 to 2 micrograms/ml) approximately twice as long as cefoxitin, that serum cefmetazole can be maintained longer at clinically significant concentrations with preadministration of probenecid, and that cefmetazole is partially eliminated by renal tubule secretion.
Topics: Adult; Cefmetazole; Cefoxitin; Drug Interactions; Half-Life; Humans; Injections, Intravenous; Male; Middle Aged; Probenecid
PubMed: 2729930
DOI: 10.1128/AAC.33.3.356 -
The American Journal of Case Reports Jul 2022BACKGROUND Cefmetazole (CMZ), containing an N-methyl-tetrazole-thiol (NMTT) side chain, is a therapeutic option for diverticulitis in Japan. Cephems containing an NMTT,...
BACKGROUND Cefmetazole (CMZ), containing an N-methyl-tetrazole-thiol (NMTT) side chain, is a therapeutic option for diverticulitis in Japan. Cephems containing an NMTT, a methyl-thiadiazol, and a thiadiazolethiol side chain are known to induce coagulation disorders. CASE REPORT A 76-year-old woman developed hypoprothrombinemia after receiving oral levofloxacin (LVFX) 250 mg q24h for 2 days followed by intravenous CMZ 2 g q8h for sigmoid diverticulitis. On day 5 of CMZ administration (after 12 doses in total), black stool was observed. On the following day (after 14 doses), prothrombin time (PT) prolongation was noted; PT and international normalized ratio (INR) were 37.1 s and 2.47, respectively. We diagnosed the patient with hypoprothrombinemia because of vitamin K deficiency caused by markedly elevated protein levels induced by vitamin K absence or antagonist-II on day 6 of CMZ administration. Intravenous vitamin K administration and CMZ cessation rapidly restored PT and led to the disappearance of black stool. CONCLUSIONS The causes of vitamin K deficiency were considered to be an impaired vitamin K cycle due to CMZ and decreased vitamin K intake because of malnutrition. These findings are consistent with CMZ's reported adverse effects. Decreased vitamin K production due to alterations in the gut bacterial flora by LVFX and CMZ was also postulated as a cause. If a bleeding tendency is noted during diverticulitis treatment with NMTT-containing cephems, switching to intravenous quinolones or carbapenems is recommended. It remains unclear how this reaction can be avoided; however, prudent monitoring of bleeding signs and PT-INR is recommended.
Topics: Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Cefmetazole; Diverticulitis; Female; Humans; Hypoprothrombinemias; Vitamin K; Vitamin K Deficiency
PubMed: 35891595
DOI: 10.12659/AJCR.936712 -
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 -
Antimicrobial Agents and Chemotherapy Oct 1990The pharmacokinetics and dose proportionality of cefmetazole were studied in 24 healthy volunteers (12 young and 12 elderly). Each volunteer received single 0.5-, 1-,... (Clinical Trial)
Clinical Trial Comparative Study
The pharmacokinetics and dose proportionality of cefmetazole were studied in 24 healthy volunteers (12 young and 12 elderly). Each volunteer received single 0.5-, 1-, and 2-g doses of cefmetazole administered intravenously over 5 min according to a three-way crossover design. Serial plasma and urine samples were collected over a 24-h period following dosing and assayed for cefmetazole by a high-performance liquid chromatography method. Results of the dose proportionality portion of the study indicated that cefmetazole pharmacokinetics are linear and proportional with dose in both age groups. Comparisons of pharmacokinetic parameters between the young and elderly groups indicated that the systemic clearance was significantly lower in elderly than in young volunteers (92.4 versus 112 ml/min). Additionally, creatinine clearance was significantly lower in elderly (74.1 ml/min) than in young (92.9 ml/min) subjects. No significant differences between age groups were observed for volume of distribution, urinary recovery, terminal half-life, nonrenal clearance, or renal clearance, although half-life was slightly prolonged in elderly volunteers relative to that in young volunteers (1.54 versus 1.34 h), and renal clearance was slightly lower in elderly than in young volunteers (83.7 versus 96.1 ml/min). Both systemic and renal clearance were significantly correlated with creatinine clearance. These results indicate that the observed age-related differences in the pharmacokinetics of cefmetazole are most likely due to differences in renal function between the two age groups. The small reduction in cefmetazole elimination in the elderly would not warrant dose adjustment in this population.
Topics: Adult; Aged; Aging; Cefmetazole; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate; Random Allocation
PubMed: 2291659
DOI: 10.1128/AAC.34.10.1944 -
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