In-depth analysis of the treatment effect and synergistic mechanism of TanReQing injection on clinical multi-drug resistant Pseudomonas aeruginosa.

Antibiotic resistance is a recognized and concerning public health issue. Gram-negative bacilli, such as Pseudomonas aeruginosa (P. aeruginosa), are notorious for their rapid development of drug resistance, leading to treatment failures. TanReQing injection (TRQ) was chosen to explore its pharmacological mechanisms against clinical multidrug-resistant P. aeruginosa (MDR-PA), given its antibacterial and anti-inflammatory properties. We revealed the expression of proteins and genes in P. aeruginosa after co-culture with TRQ. This study developed an assessment method to evaluate clinical resistance of P. aeruginosa using MALDI-TOF MS identification and Biotyper database searching techniques. Additionally, it combined MIC determination to investigate changes in MDR-PA treated by TRQ. TRQ effectively reduced the MICs of ceftazidime and cefoperazone and enhanced the confidence scores of MDR-PA as identified by mass spectrometry. Using this evaluation method, the fingerprints of standard P. aeruginosa and MDR-PA were compared, and the characteristic peptide sequence (Seq-PA No. 1) associated with flagellum was found. The phenotypic experiments were conducted to confirm the effect of TRQ on the motility and adhesion of P. aeruginosa. A combination of co-immunoprecipitation and proteome analysis was employed, and 16 proteins were significantly differentially expressed and identified as potential candidates for investigating the mechanism of inhibiting resistance in P. aeruginosa treated by TRQ. The candidates were verified by quantitative real-time PCR analysis, and TRQ may affect these core proteins (MexA, MexB, OprM, OprF, OTCase, IDH, and ASL) that influence resistance of P. aeruginosa. The combination of multiple methods helps elucidate the synergistic mechanism of TRQ in overcoming resistance of P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen closely associated with various life-threatening acute and chronic infections. The presence of antimicrobial resistance and multidrug resistance in P. aeruginosa infections significantly complicates antibiotic treatment. The expression of ß-lactamase, efflux systems such as MexAB-OprM, and outer membrane permeability are considered to have the greatest impact on the sensitivity of P. aeruginosa. The study used a method to assess the clinical resistance of P. aeruginosa using matrix-assisted laser desorption ionization time of flight mass spectrometry identification and Biotyper database search techniques. TanReQing injection (TRQ) effectively reduced the MICs of ceftazidime and cefoperazone in multidrug-resistant P. aeruginosa (MDR-PA) and improved the confidence scores for co-cultured MDR-PA. The study found a characteristic peptide sequence for distinguishing whether P. aeruginosa is resistant. Through co-immunoprecipitation and proteome analysis, we explored the mechanism of TRQ overcoming resistance of P. aeruginosa.

Observation of clinical efficacy of the cefoperazone/sulbactam anti-infective regimen in the treatment of multidrug-resistant Acinetobacter baumannii lung infection.

WHAT IS KNOWN AND OBJECTIVE: Sulbactam and sulbactam-containing ß-lactam antibiotics are often used in the treatment of Acinetobacter baumannii. We aimed to further examine the clinical efficacy of a cefoperazone/sulbactam anti-infective regimen in multidrug-resistant A. baumannii (MDRAB) lung infections. METHODS: We conducted a retrospective analysis among patients with MDRAB lung infection and complete data who were treated at the geriatric intensive care unit of Jiangsu Province Hospital from January 2018 to December 2020. We collected general information, including age, sex, APACHE II score, anti-infective course, comorbid infections in other sites, other pathogens, cefoperazone/sulbactam regimen and concomitant medications, and adverse reactions. We used microbiological changes before and after treatment to assess microbiological efficacy, defined as microbial eradication and reduction. RESULTS AND DISCUSSION: 121 patients were included, among which 96 (79.34%) were men and 25 (20.66%) were women. The median age was 76 (interquartile range [IQR] 62.5-83) years, median APACHE II score was 22 (IQR 19-26), and median treatment course was 8 (IQR 5-12.5) days. Among these patients, tigecycline was concomitantly used in 52 patients and the sulbactam dose was increased to 4 g and above in 27 patients. The microbiological efficacy of conventional cefoperazone/sulbactam with/without tigecycline in MDRAB decreased with each consecutive year and a reduction in efficacy was linearly correlated with year, which was both statistically significant (p = 0.039, 0.030, respectively). In 2020, the microbiological efficacy of a higher sulbactam dose combined with tigecycline was 75%, which was a significant improvement over the conventional dose (p = 0.028). The 3-year data showed that the microbiological efficacy of conventional cefoperazone/sulbactam 3 g eight hourly (q8h) without tigecycline was 32% and efficacy increased to 57.9% when the sulbactam dose was increased. Hence, the increased sulbactam dose significantly improved efficacy in MDRAB lung infection (p = 0.049). Different doses of sulbactam combined with tigecycline increased the microbiological efficacy of MDRAB but the differences were not statistically significant. WHAT IS NEW AND CONCLUSION: A cefoperazone/sulbactam-based anti-infective regimen showed some efficacy in MDRAB lung infection, but the microbiological efficacy of a cefoperazone/sulbactam 3 g q8h regimen decreased over time. Increasing the sulbactam dose to 4 g or more can improve efficacy. Minimum inhibitory concentration (MIC)-guided personalized medicine may be a future research direction.

Comparison of Tigecycline or Cefoperazone/Sulbactam therapy for bloodstream infection due to Carbapenem-resistant Acinetobacter baumannii.

Background: We retrospectively analyzed the effect of tigecycline and cefoperazone/sulbactam therapies on the prognosis of patients with carbapenem-resistant Acinetobacter baumannii bloodstream infection (CRAB-BSI). Methods: CRAB-BSI patients receiving tigecycline therapy or cefoperazone/sulbactam therapy between January 2012 and December 2017 was enrolled, and strict exclusion criteria were followed. The 28-day mortality of patients was analyzed. The impact of cefoperazone/sulbactam therapy on prognosis was evaluated using Cox multivariate regression analysis. The 28-day mortality of patients receiving cefoperazone/sulbactam monotherapy and cefoperazone/sulbactam-based combination therapy was also compared. Results: Three hundred forty eight patients with CRAB-BSI were enrolled in the study. Two hundred ten patients were included after applying the exclusion criteria. Of these, 135 patients received tigecycline therapy and 75 patients received cefoperazone/sulbactam therapy. The 28-day mortality of patients in the latter group was, significantly lower than that of the tigecycline group [29.3% vs. 51.9%; P = 0.001]. Cox multivariate regression analysis revealed that cefoperazone/sulbactam therapy exerted a protective effect on the prognosis of patients [hazard ratio 0.566, 95% confidence interval (0.342-0.940); P = 0.028]. Kaplan-Meier survival curve analysis indicated that the 28-day mortality of patients receiving cefoperazone/sulbactam therapy was lower than that of patients receiving cefoperazone/sulbactam monotherapy, but the difference was not significant (22.2% vs. 40%; P = 0.074). However, the mortality of patients receiving cefoperazone/sulbactam with imipenem/cilastatin was significantly lower than that of patients receiving cefoperazone/sulbactam monotherapy (P = 0.048). Conclusions: Patients treated with cefoperazone/sulbactam therapy had a better clinical outcome. The mortality of patients receiving cefoperazone/sulbactam with imipenem/cilastatin seems to be the lowest.

In vitro activity and clinical efficacy of macrolides, cefoperazone-sulbactam and piperacillin/piperacillin-tazobactam against Bordetella pertussis and the clinical manifestations in pertussis patients due to these isolates: A single-centre study in Zhejiang Province, China.

BACKGROUND AND OBJECTIVE: Macrolides are the recommended antibiotics for treating pertussis and preventing transmission. The causative bacterium, Bordetella pertussis, has high macrolide resistance and has recently circulated in China. The objective of this study was to find effective alternative antibiotics for treatment by assessing the in vitro activity and clinical efficacy of antibiotics against Bordetella pertussis. METHODS: Bordetella pertussis was confirmed by agglutination with specific antisera and mass spectrometry. The MICs of antibiotics against isolates were determined using the Etest method. Treatment outcomes were clinically and microbiologically evaluated. RESULTS: A total of 126 pertussis patients were diagnosed based on culture, 69.8% of whom were aged ≤6 months and 72.1% were treated with previous macrolides. Leucocytosis and lymphocytosis were observed in 29.4% and 54.8% of all patients, respectively. Both MIC50 and MIC90 of erythromycin, azithromycin, and clindamycin were >256mg/L, and 75.4% were highly macrolide resistant. The MIC90 of trimethoprim-sulfamethoxazole, ampicillin, ampicillin-sulbactam, cefuroxime, ceftriaxone and cefoperazone-sulbactam were 0.38mg/L, 0.25mg/L, 0.19mg/L, 12mg/L, 0.19mg/L and 0.047mg/L, respectively. The MICs of piperacillin in all of the isolations were <0.016mg/L. Of the patients treated with single cefoperazone-sulbactam or piperacillin-tazobactam, 30 of 32 (93.8%) had significantly improved clinical symptoms and 24 of 25 (96%) had negative culture results after 2 weeks of therapy. CONCLUSION: Macrolide resistance in Bordetella pertussis is a serious problem in Zhejiang Province, China. Piperacillin/piperacillin-tazobactam and cefoperazone-sulbactam have potent antibacterial activity in vitro and in vivo, and may become the alternative choice for treating pertussis caused by macrolide-resistant isolates.

Improvement of modified charcoal-cefoperazone-deoxycholate agar by addition of potassium clavulanate for detecting Campylobacter spp. in chicken carcass rinse.

The presence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) in raw poultry is one of the most common factors that interfere with the isolation of Campylobacter by cefoperazone-based selective agar. The performance of modified charcoal-cefoperazone-deoxycholate agar (mCCDA) was improved by addition of an ESBL inhibitor, potassium clavulanate (0.5 mg/L). The ability of the supplemented medium (C-mCCDA) to detect Campylobacter species from chicken carcass rinse was compared with that of normal mCCDA. The isolation rate using C-mCCDA was significantly (p<0.05) higher compared with that using mCCDA (C-mCCDA, 67 out of 120; mCCDA, 38 out of 120). Furthermore, the selectivity of the C-mCCDA as assessed by comparing the number of contaminated plates (C-mCCDA, 44 out of 120; mCCDA, 110 out of 120) and growth index (C-mCCDA, 1.76; mCCDA, 2.79) of competing flora was also better (p<0.05) than that of mCCDA.

Linum usitatissimum (linseed/flaxseed) fixed oil: antimicrobial activity and efficacy in bovine mastitis.

PURPOSE: In vitro antimicrobial activity and in vivo therapeutic efficacy of L. usitatissimum (linseed/flaxseed) fixed oil in bovine mastitis were investigated. METHOD: In vitro antimicrobial activity of L. usitatissimum fixed oil was evaluated against a number of microorganisms by disc diffusion method and MIC determination. The in vivo efficacy of the oil was evaluated in nine mastitis-affected cows divided into three groups (three in each group), following once-a-day intramammary infusion of oil, cefoperazone or an oil-cefoperazone combination for 7 days and by monitoring the California mastitis test score, somatic cell count and microbial count in milk samples. RESULTS: The in vitro antimicrobial activity of the oil against Staphylococcus aureus, Streptococcus agalactiae and Escherichia coli was comparable to that of cefoperazone while the antimicrobial activity against Enterococcus faecalis, Micrococcus luteus and Candida albicans, was greater than that of cefoperazone. In the in vivo study, the oil exhibited significant reduction in the California mastitis test score and somatic cell count in milk samples from infected udders following 7 days of intramammary administration suggesting its anti-inflammatory effect. The microbial count in milk samples was also reduced significantly following oil treatment. The effects were comparable to the treatment by cefoperazone (Mastiwock) alone or in combination with the oil. Apparently, the anti-inflammatory and antimicrobial properties of the oil contribute to its therapeutic efficacy in mastitis; the oil could be used as an alternative treatment for bovine mastitis CONCLUSION: The results suggest possible therapeutic potential of L. usitatissimum fixed oil in bovine mastitis.

Comparison of in vitro activities of ceftazidime, piperacillin-tazobactam, and cefoperazone-sulbactam, and the implication on empirical therapy in patients with cancer.

BACKGROUND: Infection is a common cause of morbidity and mortality in cancer patients. In most of these cases empirical treatment is provided because the focus of infection is not identified. Empiric antibiotics provided to these patients are based on isolates, sensitivity, and on guidelines. Here we have compared three antibiotics recommended as empirical treatment by the Infectious Disease Society of America (IDSA). AIMS: To compare the three antibiotic sensitivities for gram negative isolates at our institute. OBJECTIVE: To choose the optimal antibiotic as the empirical treatment for cancer patients developing infections. MATERIALS AND METHODS: We collected the data on isolates and antibiotic sensitivity patterns of isolates for ceftazidime, piperacillin + tazobactum, and cefoperazone from the medical oncology department. We subsequently compared the sensitivity of these three antibiotics. STATISTICAL METHODS: The isolates were mapped using the WHONET 5.4 software. The analysis was conducted using SPSS 15.0 for Windows. McNemar Chi-square test was used to compare the sensitivity percentages between any two antibiotics. The agreement between the antibiotic and the gold standard was calculated using the Kappa statistic. Two tailed p values were reported. RESULTS: The results showed that there was a difference among sensitivities for these antibiotics. It appears that the sensitivity of ceftazidime was inferior to the two other antibiotics. Also cefoperazone has better sensitivity as compared to piperacillin + tazobactum. CONCLUSION: In spite of these three antibiotics being recommended by IDSA our data suggest that it should not be followed blindly and local sensitivity data is important for formulating institutional guidelines for using antibiotics.

Aeromonas species isolated from medicinal leeches.

Aeromonas hydrophila infections are a recognized complication of the use of medicinal leeches. The authors performed an experiment designed to find a safe and practical way to sterilize the leech gut of pathogenic organisms. Leeches were incubated for a 12-hour period in solutions of antibiotic effective against A. hydrophila. The incubations in the antibiotic solutions failed to eradicate pathogenic bacteria from the gut of the leeches. The authors examined cultures of bacteria isolated from the guts of the commonly used Hirudo medicinalis (European leech) and found a wide variety of pathogenic organisms. A. hydrophila is widely believed to be the most common enteric pathogen, but the authors found A. sobria more frequently in their experiment. They also cultured the guts of the leech H. michaelseni recently used clinically in South Africa. A. caviae was the most common pathogen encountered in these leeches. A. caviae and A. sobria cause a spectra of disease similar to A. hydrophila. The authors endorse the current recommendation that all patients who have leech therapy for congested flaps or replants receive broad-spectrum prophylactic antibiotics. This appears to be the safest and simplest way to prevent leech-related infections.

[Antibacterial activity in vitro and clinical use of sulperazon].

In order to approach antibacterial activity in vitro and the efficacy of Sulperazon (SPZ) (sulbactam/cefoperazone), the sensitivity tests of 1,372 strains from clinical isolated bacteria to 17 antibiotics including SPZ were determined. The Gram negative bacteria occupied 1,035 strains (75.4) and Gram positive 337 strains (24.6%). 50 episodes of infections of major respiratory system in 43 patients were treated by SPZ. 58% of bacterial infections occurred in hematologic malignant diseases and solid tumors patients. 24% of 50 episodes were in neutropenia status. The positive rate of bac-terial cluteres was 56% in the series. 1.0-2.0 g SPZ was administered twice a day for 5-18 days, 56% of them was more than seven days (28/50 episodes). The results of susceptibility tests showed that sensitive rates were most high and the nesistant rates of SPZ were lower than these of to common Gram negative and Gram positive bacteria in third-generation cephalosporins. The efficacy rate of SPZ in clinical use was 84% (42/50 episodes), bacterial clearance rate was 89% (25/28 episodes). Three cases (6%) had temporary elevation and other adverse reactions of SPZ were not seen.

Sulbactam/cefoperazone versus cefotaxime for the treatment of moderate-to-severe bacterial infections: results of a randomized, controlled clinical trial.

We conducted a randomized, open-label, controlled, multicenter study to compare sulbactam/cefoperazone with cefotaxime in terms of efficacy and safety for the treatment of hospitalized patients with moderate-to-severe bacterial infections. More than two-thirds of the pathogens recovered from these patients produced beta-lactamase. Two hundred-seven (88.1%) of the 235 patients enrolled completed the study and were included in the efficacy and safety evaluations. One hundred-three patients received sulbactam/cefoperazone (2-4 g/d) administered in evenly divided doses every 12 hours by a 30-minute intravenous drip; 104 patients received cefotaxime (6-12 g/d) administered in evenly divided doses every 6 or 8 hours by a 30-minute intravenous drip. The overall efficacy rates (i.e., cure or markedly improved) were 95% for the sulbactam/cefoperazone group and 90% for the cefotaxime group (P = .186), whereas the bacterial eradication rates were 85% for the sulbactam/cefoperazone group and 81% for the cefotaxime group (P = .467). Both drug regimens were well tolerated. Sulbactam/cefoperazone is effective and safe for the treatment of moderate-to-severe bacterial infections caused mainly by beta-lactamase-producing organisms.

[A trial of using Cefobid (cefoperazone) in treating infections of the skin and soft tissues]. / Opyt primeneniia tsefobida (tsefoperazona) pri lechenii infektsii kozhi i miagkikh tkanei.

A clinical laboratory investigation of cefoperazon in the treatment of 27 patients with burn traumata and purulent necrotic wounds of the soft tissues of various genesis and localization was carried out. The clinical efficacy of the treatment was 75-86.6 per cent. 4 patients with extended purulent wounds of the soft tissues and bone affections were treated with cefoperazon and local application of gentacicol (a dosage form of gentamicin based on collagen with prolonged action) which provided the clinical effect in all the cases. 226 isolates from the wounds, urine, blood, sputum, pleural fluid and other substrates were tested and a rather high activity of cefoperazon against many strains of gram-positive and gram-negative organisms including Staphylococcus spp., Pseudomonas aeruginosa, Escherichia coli, Providencia sp. and Proteus spp. was revealed. The tolerance of the drug in all the cases was good.

[Effectiveness of Cefobid in pediatric practice]. / Ocena skutecznosci Cefobidu w klinice pediatrycznej.

The sensitivity to Cefobid was evaluated in vitro in 37 bacterial strains obtained from 37 patients. Good effectiveness of the drug against the strains was found in 78.3%, moderate in 13.5%, none in 8.2%. The clinical examinations were carried out in 16 children and again a high clinical effectiveness of Cefobid was found, with cure in 14 cases (87.5%). Cefobid was ineffective in 2 children with infection of Tenckhoff catheter, which required finally exchange of the catheter. No side effects of Cefobid were noted. Cefobid is a safe and effective antibiotic which may be given to small children and patients with renal failure. The broad spectrum and the possibility of drug use without dosage modification facilitate the treatment of patients with various grades of renal failure.

[Laboratory and clinical study of sulbactam/cefoperazone (SBT/CPZ) on bacterial prostatitis].

The cefoperazone and sulbactam concentrations in human prostatic fluid were measured following intravenous administration of sulbactam/cefoperazone (SBT/CPZ) and its clinical efficacy and safety in the treatment of 11 patients with acute or chronic bacterial prostatitis were evaluated. Cefoperazone concentrations in prostatic fluid (PF) one hour after an intravenous infusion of SBT/CPZ at a dose of 1 g and 2 g were 0.57 +/- 0.26 micrograms/ml and 1.37 +/- 0.86 micrograms/ml, respectively, both exceeding the MIC against most of the isolated strains from expressed prostatic secretion (EPS). The sulbactam levels in PF at doses of 1 g and 2 g of SBT/CPZ were 0.30 +/- 0.18 micrograms/ml and 0.38 +/- 0.13 micrograms/ml, respectively, both of which were high enough to potentiate antimicrobial activity of cefoperazone. The peak of MIC distribution of sulbactam/cefoperazone against E. coli (14 strains) and S. epidermidis (21 strains) isolated from EPS of patients with bacterial prostatitis was in a range of 0.1-0.2 micrograms/ml and 0.2-0.78 micrograms/ml as described for the cefoperazone concentration, respectively, which were superior to those of cefoperazone, ceftazidime and piperacillin, all compared as control, SBT/CPZ exhibited 8 fold or more potent antimicrobial activity than cefoperazone against beta-lactamase producing E. coli and CNS. Clinically, SBT/CPZ was given to 11 patients diagnosed as having bacterial prostatitis in a daily dose of 2-4 g for 5 to 8 days. The drug was found to be effective in all (100%) of 5 patients with acute prostatitis and in 3 (75.0%) of 4 patients who were judged to be assessable among 6 chronic patients. No side effects of any kind were observed in any of the patients treated. In laboratory tests, a transient thrombocytopenia was reported for one patient. SBT/CPZ is particularly useful in the treatment of acute bacterial prostatitis caused by GNR. This drug is useful for chronic prostatitis those, caused primarily by CNS which is susceptible to this agent. This drug is available as an injectable form, subjects for its appropriate usage will be those who show acute exacerbation of infection or who do not respond to oral therapy.

In-vitro and in-vivo antimicrobial activities of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain.

The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats.

[Sensitivity to cefoperazone (CEFOBID) of microorganisms isolated from diagnostic specimens]. / Wrazliwosc na cefoperazon (CEFOBID) drobnoustrojów izolowanych z materialów diagnostycznych uzyskanych od chorych.

Sensitivity of cephaperasone (CEFOBID) of 966 straits of microorganisms, isolated from 661 patients was assessed. The study was carried out according to the trial described by Bauer et al, using the Mueller-Hinton medium and original cephaperasone tests (Pfizer). Full sensitivity was found in 87.1% of the organisms. The following conclusions were made: 1. Most isolated organisms were sensitivite to cephaperasone (87.1%); E. coli (98.5%), Kl. Pneumoniae (94.8%), Atrobacter (93.1%), Enterobacter (92.8%), Klebsiella sp (92.5%). Lowered sensitivity was seen in Pseudomonas sp. (70.9%), Acinobacter (70.8%) and Alcaligenes (58.3%). 2. Cross-resistance with other cephalosporines was found in 27.8% of the cases. In 52.4% full sensitivity to cephaperasone was found, and resistance to other clinically used cephalosporines.

Cefoperazone plus mezlocillin for empiric therapy of febrile cancer patients.

Two dosing regimens of cefoperazone plus mezlocillin were compared in a prospective, randomized trial for therapy of febrile cancer patients. The two regimens were 5 g mezlocillin plus 2 g cefoperazone intravenously every four hours (higher dose) or 3 g mezlocillin plus 1 g cefoperazone intravenously every four hours (lower dose). Although the overall response rate was higher with the higher dose regimen (78 percent versus 66 percent, p = 0.04), the two regimens were comparable in patients with documented infections (72 percent versus 68 percent). Likewise, the two regimens were equally effective against those infections in which the pathogen could be determined (82 percent versus 82 percent). Serum bactericidal titers of at least 1:32 against a known pathogen were associated with a higher response rate than were titers of less than 1:32, but the higher dose regimen did not result in higher serum bactericidal titers. Hypoprothrombinemia was a side effect, especially with the higher dose regimen, before prophylactic vitamin K was routinely administered to patients. Since there were no major benefits with the use of the higher dose regimen of mezlocillin plus cefoperazone, the lower dose regimen is more appropriate for routine usage.

Cefoperazone compared with chloramphenicol in the treatment of typhoid fever.

The authors have conducted an open randomized study to compare the clinical efficacy and safety of cefoperazone with those of chloramphenicol in the treatment of typhoid fever. They studied 56 subjects (28 in each group), 36 males and 20 females, whose average age was 25.9 years. The diagnosis of typhoid fever was made when one of the at least three blood cultures performed was positive for Salmonella typhi and in the presence of a 'toxic'-like symptomatology and hyperpyrexia (39 degrees C). Moreover, several stool cultures were done and the signs and symptoms characteristic of the pathology in progress were monitored. Furthermore, the MICs of cefoperazone and chloramphenicol were determined for all the strains of S. typhi isolated in both groups. Cefoperazone was given at the mean dose of 2 g i.v. every 8 h, and chloramphenicol at the dose of 500 mg by oral route every 6 h. The results obtained were assessed statistically (Friedman's test and Fischer's test). The authors conclude that cefoperazone is as active as chloramphenicol, and the importance of this result should not be underestimated.

Cefoperazone-sulbactam combination in the treatment of urinary tract infections: efficacy, safety, and effects on coagulation.

Seventy hospitalized patients with upper urinary tract infections were treated with cefoperazone (2 gm) and sulbactam (1 gm) every 12 hours for three or more days. All but six patients also received vitamin K. Forty of the 70 patients (57%) were cured of infection at one week after treatment, 13 relapsed, 11 had reinfections, and six were lost to follow-up. There were no treatment failures. Escherichia coli was the predominant pathogen (62% of isolates). Overall there was 15% resistance to cefoperazone and all resistant isolates were susceptible to the combination of agents. Synergy was demonstrated in 26% of isolates. One uroseptic patient who had an organism resistant to both study agents, but susceptible to the combination, was cured. Two of six patients who did not receive vitamin K demonstrated abnormal coagulation patterns and one had an associated major bleeding complication. Although 12 of 64 (19%) patients who received vitamin K had at least one coagulation abnormality, there were no significant bleeding complications in this group.

The cefoperazone-sulbactam combination. In vitro qualities including beta-lactamase stability, antimicrobial activity, and interpretive criteria for disk diffusion tests.

Three concentrations of the penicillanic acid sulfone, sulbactam were tested in combination with cefoperazone against 632 recent clinical bacterial isolates. Cefoperazone was effective alone (less than or equal to 16 micrograms/mL) against 95% of Enterobacteriaceae and combined with 4 micrograms/mL sulbactam inhibited 99.5% of strains. This coverage of enteric bacilli was superior to timentin (99.1%), ceftazidime (98.2%), and tobramycin (90.9%). The minimum inhibitory concentrations (MICs) of cefoperazone-susceptible strains also were markedly decreased by sulbactam (overall MIC90s, 8.0 micrograms/mL for cefoperazone and 1.0 microgram/mL for cefoperazone and 4.0 micrograms/mL for sulbactam). Sulbactam also expanded the spectrum of cefoperazone against Acinetobacter species, some rare Pseudomonas species, and Bacteroides fragilis group species. Sulbactam had direct antimicrobial activity against the acinetobacters and Pseudomonas acidovorans, but the increased activity of cefoperazone-sulbactam against some other Pseudomonas species and anaerobes was attributed to beta-lactamase inhibition. The cefoperazone MICs against beta-lactamase producing Staphylococcus species also were lowered to the level of enzyme-deficient strains. Cefoperazone bactericidal activity was improved by 4.0 micrograms/mL sulbactam, and no antagonism was observed. beta-lactamase hydrolysis studies confirmed a slow hydrolysis of cefoperazone only by TEM beta-lactamases and a high-grade resistance to enzyme breakdown by sulbactam. Differential beta-lactamase affinity studies for cefoperazone and sulbactam showed potential efficacy and applications to plasmid-mediated TEM and OXA enzymes and only marginal effective sulbactam inhibition of Pseudomonas and Klebsiella species enzymes. Disk diffusion studies on 556 strains confirmed the applicability of the cefoperazone 75-micrograms disk to testing routine isolates other than enterococci and methicillin-resistant Staphylococcus aureus. The addition of 4.0 micrograms sulbactam/mL in a fixed concentration to dilution test systems and 15 micrograms sulbactam to the 75 micrograms cefoperazone disk were recommended for in vitro tests. Susceptibility and resistant interpretive criteria for the disk and dilution tests can be applied with confidence. Only 0.4% false-susceptibility errors and a 97.5% absolute interpretive agreement were achieved using the 75 micrograms cefoperazone/15 micrograms sulbactam disk.