Pharmacokinetics/pharmacodynamics analysis and establishment of optimal dosing regimens using unbound cefmetazole concentration for patients infected with Extended-Spectrum ß-lactamase producing Enterobacterales (ESBL-E).

STUDY OBJECTIVE: Establish methods for measuring cefmetazole (CMZ) concentrations conduct a pharmacokinetic/pharmacodynamic (PK/PD) analysis using unbound CMZ concentrations for extended-spectrum ß-lactamase producing enterobacterales (ESBL-E) and investigate optimal dosing regimens for not undergoing hemodialysis (non-HD) and undergoing hemodialysis (HD) patients. DESIGN: Prospective observational study. PATIENTS: Included patients treated with CMZ who provided written informed consent and were admitted to the Tokyo Bay Urayasu Ichikawa Medical Center between August 2021 and July 2022. MEASUREMENTS: Total and Unbound CMZ concentration was measured by high-performance liquid chromatography (HPLC) with solid-phase extraction and ultrafiltration. SETTING: Determining the CMZ dosing regimen involved modified creatinine clearance (CLCR ) with measured body weight (BW) using the Cockcroft-Gault equation. For non-HD patients, blood samples were collected during at least three points. For patients undergoing HD, 1 g was administered via intravenous infusion, or rapid intravenous injection after HD, or 30 min before the end of HD. Blood samples were collected before HD (pre-HD), and 1 and 3 h after starting HD and post-HD. All blood samples were collected at steady-state. Patient information was collected from electronic medical records. An unbound PK model was constructed for the non-HD patients. A nomogram was constructed using Monte Carlo simulations with a 90% probability of target attainment at 70% free time above the minimum inhibitory concentration (MIC). For the HD patients, a nomogram was used to determine the optimal dosing regimen for each HD schedule. MAIN RESULTS: CMZ measurement methods were established. A model analysis of unbound PK in 37 non-HD patients incorporated creatinine clearance (CLCR ) using the Cockcroft-Gault equation, albumin (ALB) for clearance and body weight (BW) for the volume of distribution. In Monte Carlo simulations, nomograms corresponding to the MIC (known and unknown) were generated for each covariate. Using the nomogram, non-HD patients with an ESBL-E MIC of 8 mg/L, a BW of 60 kg, an ALB of 25 g/L, and a CLCR of 60 mL/min required administration of 2 g every 6 h (1- and 3-h infusions). Unbound PK model parameters were calculated for 7 HD patients, and the optimal dosing regimens following PK/PD were determined for each HD schedule. In HD patients, the regimen after and during HD was established using a treatment that was effective up to an ESBL-E MIC of 4 mg/L. CONCLUSIONS: The nomogram for CMZ regimens established by PK/PD analysis of measured CMZ concentrations enables optimal CMZ dosing for ESBL-E-infected patients.

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli.

Cefmetazole is active against extended-spectrum ß-lactamase-producing Escherichia coli (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 (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum ß-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.

Bacterial susceptibility changes post national shortage of first cephalosporin in Japan: a longitudinal retrospective database study using interrupted time series analysis.

OBJECTIVES: The clinical evidence for the effect of narrow-spectrum antimicrobial shortages on bacterial susceptibility is limited. Our purposes were to determine the affects of the disruption of most of the cefazolin (CEZ) supply in Japan on the susceptibility of pathogens and to analyze how long these changes persisted after the shortage of CEZ. METHODS: We performed an interrupted time series analysis using the Japanese Infectious Disease Nationwide database. We analyzed each pathogen before and after CEZ shortage in 52 university hospitals from 2018 to 2020. May to November 2019 was designated as the implementation term for CEZ shortage. The primary outcome was the susceptibility to CEZ and other antimicrobial agents. Amongst all pathogens isolated from facilities, we identified pathogens that were tested for susceptibility to CEZ. RESULTS: Of the 26 pathogens identified, analysis was performed on a total of 36,346 isolates of five pathogens (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, and Staphylococcus aureus). Amongst four Gram-negative pathogens with low susceptibility, there were no significant immediate changes after the CEZ shortage; however, the slope change significantly increased by 1.29 to 2.69% per month and continued to improve one year after the shortage. Regarding S. aureus, which was highly susceptible at the baseline, neither immediate change nor slope was significant. CONCLUSION: This quasi-experimental analysis using a nationwide-large database revealed that restriction of use because of narrow-spectrum antimicrobial shortages may lead to improved susceptibility over the subsequent year. The results suggest that temporary switching of antimicrobial agents on a national scale could be effective.

Cefmetazole as an Alternative to Carbapenems Against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Infections Based on In Vitro and In Vivo Pharmacokinetics/Pharmacodynamics Experiments.

PURPOSE: Cefmetazole (CMZ) has received attention as a pharmaceutical intervention for extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) infections. This study aimed to investigate the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of CMZ against ESBL-EC. METHODS: The susceptibility and time-killing activity of CMZ against clinically isolated ESBL-EC (EC9 and EC19) were determined in vitro. The optimal PK/PD index and its target value were calculated based on the results of a PK study in healthy mice and PD study in neutropenic murine thigh infection model mice. RESULTS: The minimum inhibitory concentrations (MICs) of CMZ against EC9 and EC19 were 2.0 and 1.0 µg/mL, respectively. Time-kill studies showed that colony-forming units decreased in a time-dependent manner at CMZ concentrations in the range of 4-64 × MIC. In in vivo PK/PD studies, the antibacterial effect of CMZ showed the better correlation with the time that the free drug concentration remaining above the MIC (fT>MIC), with the target values for a static effect and 1 log10 kill reduction calculated as 57.6% and 69.6%, respectively. CONCLUSION: CMZ possesses time-dependent bactericidal activities against ESBL-EC and is required to achieve "fT>MIC" ≥ 69.6% for the treatment of ESBL-EC infections.

In Vitro Efficacy of Meropenem-Cefmetazole Combination Therapy against New Delhi Metallo-ß-lactamase-producing Enterobacteriaceae.

BACKGROUND: Limited treatment options complicate management of infections with New Delhi metallo-ß-lactamase (NDM)-producing organisms. The efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) was assessed against NDM-producing Enterobacteriaceae. MATERIALS AND METHODS: Twelve Escherichia coli clinical isolates harbouring blaNDM-1 and a positive control E. coli BAA-2469 harbouring blaNDM-1 were studied. Minimum inhibitory concentrations (MICs) of MEM, ertapenem (ERT) and CMZ were determined by broth microdilution. Checkerboard and time-kill assays were performed to confirm the in vitro efficacy of the MEM/CMZ combination. Scanning electron microscopy, kinetic studies and whole-genome sequence analysis were used to determine the antimicrobial resistance mechanisms. RESULTS: MICs of MEM, ERT and CMZ in monotherapy ranged from 8 to 32, 16 to 128, and 32 to 512 µg/mL, respectively. In the checkerboard assay, MEM/ERT resulted in no synergy, whereas MEM/CMZ showed a synergistic effect in all the tested isolates. Furthermore, the MIC of MEM in combination decreased by 2- to 8-fold compared with that of MEM alone. The time-kill study revealed a bactericidal effect in 4 of 13 isolates at 24 h. Scanning electron microscopy showed spheroidisation of the bacterial cell in the MEM/CMZ combination; this was not observed in single antibiotic conditions. Kinetic studies indicated CMZ was a better antagonist for NDM-1 than ERT. Whole-genome sequence analysis did not reveal any explainable differences between isolates susceptible and those non-susceptible to combination therapy. CONCLUSION: In vitro studies showed the potential effectiveness of MEM/CMZ combination therapy against NDM-producing organisms.

Bactericidal efficacy of meropenem in combination with cefmetazole against IMP-producing carbapenem-resistant Enterobacteriaceae.

OBJECTIVE: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). RESULTS: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 µg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.

In Vitro Effectiveness of Meropenem and Cefmetazole Combination Treatment Against KPC-2-Producing Enterobacteriaceae.

Purpose: Optimal treatment regimens are yet to be established for carbapenemase-producing Enterobacteriaceae (CPE). We assessed the in vitro efficacy of meropenem (MEM) and cefmetazole (CMZ) combination treatment against blaKPC-2-positive Enterobacteriaceae, in comparison with that of double-carbapenem therapy using ertapenem (ERT). Materials and Methods: We performed checkerboard assay for 10 blaKPC-2-positive clinical isolates and Klebsiella pneumoniae BAA-1705 (possessing blaKPC-2), with synergistic effect being defined by a fractional inhibitory concentration index of ≤0.5. Subsequently, we conducted time-kill assays using K. pneumoniae BAA-1705 with an initial inoculum of 104-107 colony forming unit (CFU)/mL. Bactericidal effect was defined as the reduction of initial bacterial count by ≥103 CFU/mL in 24 hr. Finally, we applied scanning electron microscopy to observe morphological changes induced by the combination of MEM and CMZ. Results: Checkerboard assays revealed a synergistic effect in 7 out of 11 blaKPC-2 -positive Enterobacteriaceae when the MEM and CMZ combination was used, and no effect when the MEM and ERT combination was used. The minimum inhibitory concentration of MEM decreased 4-8-fold when combined with CMZ. Time-kill assays with an initial inoculum of 5 × 105 CFU/mL revealed regrowth under the combination of MEM and ERT (0.25 × minimum inhibitory concentration [MIC] each), whereas the combination of 0.25 × MIC each of MEM and CMZ exhibited bactericidal effect. Scanning electron microscopy results demonstrated that the combination of 0.5 × MIC MEM and 0.5 × MIC CMZ facilitated bacterial cell lysis compared with each antibiotic alone. Conclusion: The combination therapy using MEM and CMZ potentially has bactericidal effect against KPC-producing Enterobacteriaceae.

New antibiotic regimen for preterm premature rupture of membrane reduces the incidence of bronchopulmonary dysplasia.

AIM: The optimal antibiotic regimen for preterm premature rupture of membrane (pPROM) is still unclear. This study aimed to determine the effects of ampicillin-sulbactam (SBT/ABPC) and azithromycin (AZM) on the incidence of bronchopulmonary dysplasia (BPD). METHODS: This retrospective study included women with singleton gestations and a diagnosis of pPROM between 22 and 27 weeks of gestation. In patients presenting with a high risk of intra-amniotic infection between January 2011 and May 2013, piperacillin or cefmetazole + clindamycin (regimen 1 group; n = 11) was administered, whereas SBT/ABPC and AZM (regimen 2 group; n = 11) were administered in patients presenting a similar risk between June 2013 and May 2016. RESULTS: The incidence of moderate or severe infant BPD in the regimen 2 group was significantly lower than that in the regimen 1 group, even when adjusted for gestational age at the time of rupture of membrane, with an odds ratio (95% confidence interval) of 0.02 (1.8 × 10-5 -0.33). The incidence of BPD and total days on mechanical ventilation were significantly lower in the regimen 2 group than in the regimen 1 group. No significant differences were seen in other morbidities. CONCLUSION: In patients with pPROM between 22 and 27 weeks of gestation, the administration of SBT/ABPC and AZM may improve the perinatal outcomes.

Single-molecule imaging reveals modulation of cell wall synthesis dynamics in live bacterial cells.

The peptidoglycan cell wall is an integral organelle critical for bacterial cell shape and stability. Proper cell wall construction requires the interaction of synthesis enzymes and the cytoskeleton, but it is unclear how the activities of individual proteins are coordinated to preserve the morphology and integrity of the cell wall during growth. To elucidate this coordination, we used single-molecule imaging to follow the behaviours of the two major peptidoglycan synthases in live, elongating Escherichia coli cells and after perturbation. We observed heterogeneous localization dynamics of penicillin-binding protein (PBP) 1A, the synthase predominantly associated with cell wall elongation, with individual PBP1A molecules distributed between mobile and immobile populations. Perturbations to PBP1A activity, either directly through antibiotics or indirectly through PBP1A's interaction with its lipoprotein activator or other synthases, shifted the fraction of mobile molecules. Our results suggest that multiple levels of regulation control the activity of enzymes to coordinate peptidoglycan synthesis.

Antimicrobial Susceptibility of Microorganisms Isolated from Periapical Periodontitis Lesions.

Periapical periodontitis usually results from microbial infection, with these microorganisms occasionally migrating to the root canal, which can lead to further, potentially life-threatening, complications. Here, the susceptibility of 27 bacterial strains to various antimicrobial agents was evaluated. These strains comprised 13 species; 16 of the strains were clinical isolates from periapical lesions. Each strain was inoculated onto blood agar plates containing one of the antimicrobial agents. The plates were incubated anaerobically at 37°C for 96 hr and the minimal inhibitory concentrations (MICs) determined. Ten strains required an MIC of 32 µg/ml or greater for amoxicillin, 6 for cefmetazole, and 5 for cefcapene among ß-lactam antibiotics; 8 strains required an MIC of 32 µg/ml or greater for clindamycin, 4 for azithromycin, and 11 for clarithromycin among macrolide antibiotics; 3 strains required an MIC of 32 µg/ml or greater for ciprofloxacin and 2 for ofloxacin among fluoroquinolones. The effect of cefcapene on 5 strains was evaluated after biofilm formation to investigate the relationship between biofilm formation and susceptibility. All strains showed a decrease in susceptibility after biofilm formation. The results revealed that several antimicrobial agents commonly used in a clinical setting, including amoxicillin, cefmetazole, and clindamycin, are potentially effective in the treatment of orofacial odontogenic infections. The development of resistant strains, however, means that this can no longer be guaranteed. In addition, azithromycin, ciprofloxacin, and ofloxacin were more effective than the 3 ß-lactam antibiotics tested. These results suggest that sensitivity testing is needed if odontogenic infections are to be treated safely and effectively.

In vitro activities and detection performances of cefmetazole and flomoxef for extended-spectrum ß-lactamase and plasmid-mediated AmpC ß-lactamase-producing Enterobacteriaceae.

To investigate the in vitro activities of cephamycins (cefmetazole and flomoxef) for extended-spectrum ß-lactamase (ESBL)- and plasmid-mediated AmpC ß-lactamase (pAmpC)-producing Enterobacteriaceae, a total of 574 third-generation cephalosporin-resistant clinical isolates were collected at a Japanese multicenter study. PCR and sequencing identified 394 isolates with only ESBL genes, 63 isolates with only pAmpC genes, and 6 isolates with both ESBL and pAmpC genes. blaCTX-M types predominated 95.5% of the ESBL genes, and blaCMY-2 predominated 91.3% of the pAmpC genes. The MIC50/90 values of cefmetazole and flomoxef were ≤ 1/4 and ≤ 1/≤ 1 µg/mL for isolates with only ESBL genes, respectively, and 16/>16 and 8/16 µg/mL for isolates with only pAmpC genes, respectively. Flomoxef ≥ 4 µg/mL had the best screening performance for the detection of isolates with pAmpC genes. Flomoxef had better in vitro activities against ESBL-producing Enterobacteriaceae and provided a clearer distinction between ESBL and pAmpC-producing Enterobacteriaceae compared to cefmetazole.

Multicenter retrospective study of cefmetazole and flomoxef for treatment of extended-spectrum-ß-lactamase-producing Escherichia coli bacteremia.

The efficacy of cefmetazole and flomoxef (CF) for the treatment of patients with extended-spectrum ß-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.

[Evaluation of Antibiotics for the Treatment of Bacteremia Due to Extended-spectrum ß-Lactamase-producing Escherichia coli].

Recently, extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has been more frequently isolated from blood specimens than in the past. In this study we investigated a panel of therapeutic agents used to treat 37 patients with ESBL-producing E. coli bacteremia. Antimicrobial agents administered as definitive therapy displayed higher efficacy rates than when empiric therapy was administered (efficacy rates, 95.7% vs. 62.5%). The success rate of carbapenem was 95.8% (23/24) in patients with ESBL-producing E. coli bacteremia. In addition, the success rate of cefmetazole against ESBL-producing E. coli sensitive to this drug was 87.5% (7/8). In conclusion, patients at high risk of infection due to ESBL-producing E. coli should be empirically treated with carbapenem antibiotics. In addition, cefmetazole may be a treatment option for patients with ESBL-producing E. coli bacteremia.

Non-cytotoxic nanomaterials enhance antimicrobial activities of cefmetazole against multidrug-resistant Neisseria gonorrhoeae.

The emergence and spread of antibiotic-resistant Neisseria gonorrhoeae has led to difficulties in treating patients, and novel strategies to prevent and treat this infection are urgently needed. Here, we examined 21 different nanomaterials for their potential activity against N. gonorrhoeae (ATCC 49226). Silver nanoparticles (Ag NPs, 120 nm) showed the greatest potency for reducing N. gonorrhoeae colony formation (MIC: 12.5 µg/ml) and possessed the dominant influence on the antibacterial activity with their properties of the nanoparticles within a concentration range that did not induce cytotoxicity in human fibroblasts or epithelial cells. Electron microscopy revealed that the Ag NPs significantly reduced bacterial cell membrane integrity. Furthermore, the use of clinical isolates of multidrug-resistant N. gonorrhoeae showed that combined treatment with 120 nm Ag NPs and cefmetazole produced additive effects. This is the first report to screen the effectiveness of nanomaterials against N. gonorrhoeae, and our results indicate that 120 nm Ag NPs deliver low levels of toxicity to human epithelial cells and could be used as an adjuvant with antibiotic therapy, either for topical use or as a coating for biomaterials, to prevent or treat multidrug-resistant N. gonorrhoeae.

Serum concentrations of antibiotics during severe invasive surgery such as esophagectomy for esophageal cancer.

This study was performed to confirm the antibiotic regimen during a severe invasive surgery, such as esophagectomy, with a long procedure and a large amount of normal volumes of infusion. Ten patients with esophageal cancer were enrolled in this study, and cefmetazole sodium concentrations in serum were measured during esophagectomy. The ranges of minimum inhibitory concentrations for 90% of isolates of cefmetazole sodium for microorganisms in our institutions for 8 years were investigated. The maximum concentration was 83.9 µg/mL just after the completion of infusion, and its half-life was 1.5 hours. Serum concentration of cefmetazole sodium was kept above 16 µg/mL for 4 hours during esophagectomy. It was kept above 32 µg/mL for 2.5 hours after injection. There are almost no differences in the pharmacokinetics of cefmetazole sodium between common use and during esophagectomy. In addition, additive infusion of antibiotics 4 hours after the first infusion was recommended during esophagectomy.

The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.

OBJECTIVES: Urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are on the increase. Although cefmetazole is stable in vitro against the hydrolyzing activity of ESBLs, no clinical study has ever evaluated its role in infections caused by these organisms. We therefore evaluated the efficacy of cefmetazole compared to carbapenems against pyelonephritis caused by ESBL-producing Enterobacteriaceae. METHODS: A retrospective chart review was conducted at a tertiary care hospital from August 2008 to July 2010. Chart reviews were done for patients with ESBL-producing organisms in urine identified in the microbiology database. Patients who were treated with cefmetazole were compared to those treated with carbapenems. The clinical and bacteriological cure rates at 4 weeks after completion of therapy were evaluated. RESULTS: Two hundred and fifty-six urine cultures growing ESBL-producing organisms were identified during the study period. Ten patients treated with cefmetazole and 12 patients treated with carbapenems were evaluated. There was no difference in clinical (9/10 vs. 12/12, p = 0.46) or bacteriological cure rate (5/7 vs. 6/7, p = 1.00) at 4 weeks after the completion of therapy. There was no difference in the incidence of adverse effects (2/10 vs. 2/12, p = 1.00). CONCLUSIONS: Cefmetazole may be a useful option for the treatment of UTIs caused by ESBL-producing organisms. Prospective and larger sized studies are needed to confirm our findings.

[Distribution of anaerobes in periodontal abscess and its resistance to antibiotics].

OBJECTIVE: To isolate and culture the predominant anaerobes from the periodontal abscesses, and to test the antibiotic susceptibility and drug resistant genes of the strains. METHODS: The isolated strains were identified by both API20A biochemical method and polymerase chain reaction (PCR) method. The antibiotic susceptibility test was performed by agar dilution method. The resistant genes of the drug-resistant strains obtained were screened by PCR. RESULTS: The anaerobes were detected in 48% (28/58) of the samples and Prevotella melaninogenica (Pm) was mostly identified in 43% (12/28). API20A biochemical method had 82% (23/28) agreement with the 16SrRNA method in identification rate. Anaerobes were resistant to metronidazole, clindamycin and cefmetazole. The erythromycin-resistant methylase genes F (ermF) gene was detected in three of eight clindamycin resistant strains. None of them was found coded on bacterial plasmids. However, no metronidazole resistant gene was detected on drug resistant strains. CONCLUSIONS: Pm was the predominant species dectected in the periodontal abscess of the patients. The antibiotic agents should be used based on the genotypes and general condition of the patients.

[Fundamental study on the selection of antimicrobial prophylactic agents in abdominal surgery].

Most infections after abdominal operations are endogenous and occur by disseminating bacteria present in the intestinal tract during operation. The risk of developing surgical site infection after abdominal operations is related to the extent of intestinal contamination during operation and to the density and type of bacteria in the intestinal tract. Although antimicrobial prophylactic agents must be active against contaminating bacteria during operation, it should not cover all contaminating bacteria but Staphylococcus aureus except MRSA, Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus spp. and Bacteroides spp. As the isolation rate and type of bacteria from primary abdominal infections such as perforated peritonitis and biliary tract infection are resemble to those of bacteria contaminating during operations, antimicrobial prophylactic agents could be chosen considering activities against bacteria isolated from primary infections. According to the isolation rates of these bacteria and antibiotic susceptibilities, cefotiam (CTM) is considered to have most strong activities as prophylactic agent for abdominal surgery, followed by cefmetazole (CMZ) and cefazolin (CEZ), in this order. In order to establish the fundamental principle of antimicrobial prophylaxis in surgery, these results should be evaluated by clinical prospective randomized studies in the near feature.

[Surveillance of susceptibility of clinical isolates to cefmetazole between 2000 and 2003].

For the post-marketing surveillance of cefmetazole (CMZ, Cefmetazon), MICs of injectable beta-lactam antibacterials including CMZ against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 574 isolates of 13 species were tested, 548 isolates of the same 13 species were tested in the second surveillance from April 2001 to March 2002, and 654 isolates of the same 13 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of CMZ were observed in these surveillances spanning three years. The activity of CMZ in this study was comparable to that in the studies conducted before Cefmetazon was launched. This result suggests that CMZ still maintains potent activity. Changes in percent resistance of each species to CMZ (MIC of CMZ > or = 32 microg/ml) were as follows: methicillin-susceptible Staphylococcus aureus (MSSA, 0.0% --> 0.0% --> 0.0%), methicillin-resistant Staphylococcus aureus (MRSA, 72.9% --> 87.2% --> 88.7%), Staphylococcus epidermidis (18.5% --> 31.6% --> 14.3%), coagulase-negative Staphylococcus spp. (CNS, 13.3% --> 18.2% --> 21.4%), Escherichia coli (3.6% --> 0.8% --> 2.1%), Klebsiella pneumoniae (3.4% --> 3.8% --> 2.1%), Klebsiella oxytoca (0.0% --> 0.0% --> 0.0%), Proteus mirabilis (2.3% --> 2.1% --> 0.0%), Proteus vulgaris (13.6% --> 6.7% --> 0.0%), Morganella morganii (7.3% --> 0.0% --> 14.0%), Providencia spp. (12.5% --> 0.0% --> 18.2%), Peptostreptococcus spp. (0.0% --> 0.0% --> 0.0%), Bacteroides fragilis (10.3% --> 10.8% --> 17.1%), Bacteroides spp. (78.6% --> 87.5% --> 62.5%). The Change in percent resistance of MRSA, other CNS, and B. flagiris tended to increase. It is necessary to pay much attention to trends observed in these species. Compared to other drugs tested, against MSSA, the activity of CMZ was inferior to that of CEZ, CTM, and FMOX and superior to that SBT/CPZ. Against MRSA, S. epidermidis, and CNS, the tested drugs exhibited little activity. Against Gram-negative bacteria, the activity of CMZ was almost superior to that of CEZ and CTM, and inferior to that of FMOX. Against B. flagiris and other Bacteroides spp., the activity of CMZ was almost superior to that of CEZ and CTM, and comparable to or inferior to that of SBT/CPZ and FMOX.

Infections of cefotaxime-resistant and cefmetazole-susceptible Escherichia coli and Klebsiella pneumoniae in children.

A search of the computerized database at the National Taiwan University Hospital was made for cefotaxime-resistant and cefmetazole-susceptible isolates of Escherichia coli and Klebsiella pneumoniae (which may be extended-spectrum beta-lactamase-producing strains) in pediatric wards and intensive care units between 1999 and 2001. Fourteen infectious episodes attributed only to study bacteria were identified, including 7 episodes of bacteremia. Nine patients (64.3%) had underlying medical conditions: 3 were premature babies, 3 were immunodeficient, 2 had malignancy, and 2 had a congenital heart disease with active heart failure even after surgery. Among the 7 patients with bacteremias, 5 may be catheter-related; 6 were treated with carbapenems and 1 was treated with cefmetazole successfully, with or without the removal of the catheter. Before the acquisition of the infection, a history of stay in an intensive care unit within 4 weeks was noted in 10 cases (71.4%); a history of use of extended-spectrum cephalosporins within 4 weeks was also noted in 6 cases (42.9%). Cefmetazole, with or without an aminoglycoside, was clinically effective in 6 cases (42.8%). Except for 1 episode of pneumonia that ended in mortality, all of the infectious episodes were successfully treated. The mortality rate was 7.1%.