Activity Of Cefoperazone Research Articles

Comparing the Outcomes of Cefoperazone/Sulbactam-Based and Non-Cefoperazone/Sulbactam-Based Therapeutic Regimens in Patients with Multiresistant Acinetobacter baumannii Infections-A Meta-Analysis.

The addition of sulbactam restores the complete range of cefoperazone activity against bacteria and extends its spectrum of action to include the Acinetobacter species. The effectiveness of cefoperazone/sulbactam against multiresistant Acinetobacter baumannii has not been investigated. The purpose of the current meta-analysis was to compare the efficacy of cefoperazone/sulbactam-based therapeutic regimens and non-cefoperazone/sulbactam-based therapeutic regimens in the treatment of multiresistant Acinetobacter baumannii infections. The current meta-analysis of 10 retrospective studies provides evidence that cefoperazone/sulbactam-based therapeutic regimens are superior to non-cefoperazone/sulbactam-based therapeutic regimens in terms of 30-day mortality and clinical improvement in patients with multiresistant Acinetobacter baumannii infections. The risk of mortality was reduced by 38% among multiresistant Acinetobacter baumannii infections in patients who received cefoperazone/sulbactam-based therapeutic regimens. The cefoperazone/sulbactam-based combination therapy was superior to the cefoperazone/sulbactam monotherapy in terms of 30-day mortality when both therapeutic regimens were compared to the tigecycline monotherapy in patients with multiresistant Acinetobacter baumannii infections.

A Rare Case Series on Cefoperazone Sulbactam Induced Uremia: A Matter of Concern and Awareness

Uraemia is a clinical syndrome marked by elevated concentrations of urea in the blood and is associated with fluid, electrolyte, hormone imbalances and metabolic abnormalities. Cefoperazone + sulbactam is a combination of two medicines: cefoperazone and sulbactam. Cefoperazone is an antibiotic that works by preventing the formation of the bacterial protective covering, which is essential for the survival of bacteria [1]. Sulbactam is a beta-lactamase inhibitor that reduces resistance and enhances the activity of cefoperazone against bacteria [2].
 Pharmaceutical agents play a central role in diagnostic and therapeutic activities for patient care. However, all agents carry the risk of adverse drug effects. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that negatively impacts patient morbidity and mortality [3]. Recognizing adverse effects is important for administering appropriate drug doses, implementing preventive strategies, and discontinuing the offending agent when toxicity occurs [2]. In most cases, nephrotoxicity leads to discontinuation of the causative drug, thereby limiting treatment options.
 One of the biggest challenges lies in our ability to identify nephrotoxicity in its early stages. Monitoring serum creatinine and blood urea nitrogen (BUN) levels is an effective method for identifying renal diseases [4]. In this study, the authors report three cases of isolated cefoperazone-sulbactam-induced uraemia in patients without chronic kidney disease (CKD). A Naranjo assessment score of 5 was obtained for the three case scenarios, indicating a probable relationship between the patient’s uraemia and use of the suspected drug.

Correlation Between Cefoperazone/Sulbactam MIC Values and Clinical Outcomes of Escherichia coli Bacteremia.

The clinical efficiency of cefoperazone/sulbactam (CPZ/SUL) against Escherichia coli bacteremia was unknown. This study aimed to explore the relationship between CPZ/SUL MIC values and clinical outcomes in Escherichia coli bacteremia. A multicenter, retrospective, observational cohort study was conducted in Taiwan between January 2015 and December 2020. Patients treated with CPZ/SUL for E.coli bacteremia were enrolled in the analysis. The CPZ/SUL MICs were determined byusing the agar dilution method. The primary outcome was 30-day mortality. Among 247 isolates, 160 (64.8%) isolates were susceptible, 8 (3.2%) were intermediate, and 79 (32.0%) were resistant to cefoperazone. The activity of cefoperazone against cefoperazone-non-susceptible E.coli (n = 87) was restored upon combination with sulbactam, with susceptibility ranging from 0% to 97.7%. The 30-day mortality was 4.5% (11/247) and overall clinical success rate was 91.9% (227/247). Multivariate Cox proportional-hazards model revealed that heart failure [adjusted relative risk (ARR), 5.49; 95% confidence interval (CI) 1.31-23.02; p = 0.020], malignancy (ARR 7.50; 95%CI 2.02-27.80; p = 0.003), SOFA score (ARR 1.29; 95%CI 1.09-1.52; p = 0.003), and CPZ/SUL MIC ≥ 64mg/L (ARR 11.31; 95%CI 1.34-95.52; p = 0.026) were independently associated with 30-day mortality. No statistically significant differences in 30-day mortality were found between groups with or without cefoperazone susceptibility (3.4% vs. 5.0%, p = 0.751, respectively). Patients with E.coli bacteremia who were treated with CPZ/SUL had a favorable outcome when the MICs of the isolates were ≤ 16mg/L and a high risk of mortality with MICs ≥ 64mg/L.

Cefoperazone/sulbactam: New composites against multiresistant gram negative bacteria?

Sulbactam, a class A β-lactamase inhibitor, added to cefoperazone either at a fixed 8mg/L level of sulbactam or at a level of fixed cefoperazone: sulbactam ratio (2:1) would constitute a combination form of cefoperazone/sulbactam, which has better activities against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii than cefoperazone alone. Cefoperazone/sulbactam (1:1 or 1:2) has greater in-vitro activity against most multidrug-resistant organisms (ESBL- and AmpC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii except for carbapenem-resistant P. aeruginosa) than a 2:1 ratio. However, increased sulbactam concentration may induce AmpC production. Besides, sulbactam concentration might not be readily achievable in serum if the susceptibility rates were defined by the breakpoints of higher sulbactam composites, such as ≤16/16 (1:1) or 16/32 (1:2) mg/L. Carbapenemases (KPC-, OXA-type enzymes and metallo-β-lactamases) can't be inhibited by sulbactam. Some in-vitro studies showed that increasing sulbactam composites of cefoperazone/sulbactam had no effect on carbapenem-resistant P. aeruginosa, suggesting the presence of carbapenemases or AmpC overproduction that could not be overcome by increasing sulbactam levels to recover cefoperazone activity. Sulbactam alone has good intrinsic activity against carbapenem-resistant Acinetobacter strains sometimes even in the presence of carbapenemase genes, suggesting unsteady levels of carbapenemases. In conclusion, appropriate composites of cefoperazone and β-lactamase inhibitor sulbactam may expand the clinical use if the pharmacokinetic optimization could be achieved in the human serum.

An adapted LC-MS/MS method for the determination of free plasma concentration of cefoperazone in children: Age-dependent protein binding

Antimicrobial activity of cefoperazone, a high protein bound cephalosporin, depends on its unbound concentration. However, the protein binding data of cefoperazone in children is limited, making it challenging to optimize antimicrobial therapy in pediatric clinical practice. Furthermore, a validated method to measure the free part in children is unavailable with the small volume of samples that can be obtained. Therefore, in the present study, we developed and validated an LC-MS/MS method for the determination of free cefoperazone in children. In this study, 70 μL of plasma was used to prepare the ultrafiltrate (only containing the free drug). Chromatographic separation of the analyte was achieved on a C18 column using gradient elution with a mobile phase of acetonitrile and water (0.1% formic acid). Negative electrospray ionisation in the multiple reaction monitoring mode was applied for the detection of cefoperazone and ceftiofur (internal standard). The calibration curve was prepared in the range of 5–5000 ng/mL with excellent linearity. For each level of quality control samples, the intra- and inter-day precision (CV) was below 9.0%, and the accuracy ranged from 91.5% to 105.0%. The matrix effect was less than 11.7%, and the recovery was between 92.9% and 95.9% of cefoperazone. The validated method has been successfully applied to the determination of free plasma concentration of cefoperazone in pediatric patients. The results of the unbound fraction showed considerable individual variability (range: 8.1–48.0%). The correlation analysis showed that age and albumin had significant effects on the protein binding of cefoperazone.

In vitro activity of cefoperazone and cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.

BackgroundThis study aimed to investigate the in vitro activity of cefoperazone–sulbactam against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and to evaluate the antibiotic resistance mechanisms of these bacteria.Materials and methodsIn total, 21 isolates of carbapenem-resistant P. aeruginosa and 15 isolates of carbapenem-resistant A. baumannii with different pulsed-field gel electrophoresis types were collected for assessment of the in vitro antibacterial activities of cefoperazone and cefoperazone–sulbactam and the associated resistance mechanisms of the bacteria.ResultsFor carbapenem-resistant P. aeruginosa, the minimum inhibitory concentration (MIC) value and antibiotic susceptibility rate were similar for cefoperazone and cefoperazone–sulbactam (at 1:1 and 2:1 ratios). In contrast, for carbapenem-resistant A. baumannii, the MIC values, including the MIC range, MIC that inhibited 50% of isolates (MIC50) and MIC that inhibited 90% of isolates (MIC90), were reduced after treatment with sulbactam and cefoperazone. We screened resistance genes, including VIM-2, OXA-2 and OXA-10, in 21 carbapenem-resistant P. aeruginosa isolates. Only one (4.8%) of the isolates showed expression of VIM-2, and neither the OXA-2 nor the OXA-10 gene was detected. However, 20 (95.2%) isolates among the carbapenem-resistant P. aeruginosa isolates selected for oprD sequencing showed the phenomenon of nucleotide substitution or deletion. Among 15 carbapenem-resistant A. baumannii isolates, we found that ten (66.7%) isolates had concomitant expression of the OXA-23 and ISAba1-OXA-23 genes, and six (40.0%) isolates had expression of the OXA-24-like gene. All 15 isolates had OXA-51-like gene expression, and only 1 (6.7%) isolate had ISAba1-OXA-51-like gene expression. None of the isolates contained the IMP-1, IMP-8, KPC, NDM, VIM-1 or OXA-48 genes.ConclusionThe in vitro antibacterial activity of cefoperazone against carbapenem-resistant A. baumannii can be enhanced by adding sulbactam to cefoperazone, but the addition does not affect carbapenem-resistant P. aeruginosa. This significant difference can be explained by the different resistance mechanisms of carbapenem-resistant A. baumannii and P. aeruginosa.

Appropriate composites of cefoperazone-sulbactam against multidrug-resistant organisms.

ObjectivesThis study aims to assess the in vitro activity of different cefoperazone–sulbactam ratios against different multidrug-resistant organisms (MDROs).Materials and methodsMinimum inhibitory concentrations (MICs) and susceptibility rates of cefoperazone, sulbactam and cefoperazone–sulbactam at fixed ratios of 2:1, 1:1 and 1:2 against 344 MDRO clinical isolates, including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n=58), ESBL-producing Klebsiella pneumoniae (n=58), carbapenem-resistant Enterobacteriaceae (n=57), carbapenem-resistant Pseudomonas aeruginosa (n=49) and carbapenem-resistant Acinetobacter baumannii (n=122), were measured.ResultsCombined treatment with sulbactam and cefoperazone resulted in decreased MIC50 values across all MDROs, as well as decreases in most MIC90 values, except for carbapenem-resistant Enterobacteriaceae and carbapenem-resistant P. aeruginosa (MIC90 values remained >64 mg/L). Susceptibility rates of treatment with cefoperazone alone against all MDROs were much lower than that of cefoperazone–sulbactam combination (all P<0.05), except in carbapenem-resistant P. aeruginosa. Additionally, the susceptibility rate gradually increased as the ratio of cefoperazone–sulbactam was adjusted from 2:1 to 1:1 and to 1:2 for carbapenem-resistant Enterobacteriaceae, ESBL-producing K. pneumoniae and carbapenem-resistant A. baumannii. There were no significant ratio-dependent changes in susceptibility rates with cefoperazone–sulbactam in carbapenem-resistant P. aeruginosa.ConclusionAdding sulbactam enhances cefoperazone activity against most MDROs excluding carbapenem-resistant P. aeruginosa, and the activity of cefoperazone–sulbactam against these MDROs is greatest at a ratio of 1:2, followed by ratios of 1:1 and 2:1.

The impact of inoculum size on the activity of cefoperazone-sulbactam against multidrug resistant organisms.

This study aims to assess the invitro activity of cefoperazone alone and different cefoperazone-sulbactam ratios against different inoculum sizes of multidrug resistant organisms. Minimum inhibitory concentrations (MICs) of cefoperazone, cefoperazone-sulbactam at fixed ratio of 1:1 and 2:1 against a normal inoculum size of 5×105CFU/ml and a high inoculum size of 5×107CFU/ml were measured. Each 33 isolates of extended-spectrum β-lactamases (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae, carbapenem-resistant E. coli, and carbapenem-resistant Pseudomonas aeruginosa and a total of 122 isolates of carbapenem-resistant Acinetobacter baumannii were collected. After the addition of sulbactam at a 1:1 ratio, most MIC50 and MIC90 values decreased. Cefoperazone-sulbactam at a 1:1 ratio had a higher susceptibility rate against ESBL-producing E. coli, carbapenem-resistant E. coli, and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2:1 ratio (all P<0.05). For ESBL-producing E. coli, the susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 97.0 to 87.9% and 90.9 to 60.6%, for normal to high inoculum, respectively. For ESBL-producing K. pneumoniae, both susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 75.8%, and 63.6% at normal inoculum to 51.5% and 42.4% at high inoculum. Cefoperazone-sulbactam at a 1:1 ratio has greater invitro activity against most multidrug resistant organisms than cefoperazone-sulbactam at a 2:1 ratio. Such combinations were not influenced by the inoculum size of ESBL-producing E. coli and K. pneumoniae and could be a therapeutic option for treating severe infections.

Influence of hybrid inorganic/organic mesoporous and nanostructured materials on the cephalosporins’ efficacy on different bacterial strains

The aim of this study was to investigate the effect of different hybrid inorganic-organic micro- and nanomaterials (Fe(3)O(4)/PEG(600), Fe(3)O(4)/C(12), ZSM-5) on the antibacterial activity of different cephalosporins against Gram-positive and Gram-negative bacterial strains. The synergic effect of the studied materials was demonstrated by the increase in the growth inhibition zones diameter. All tested hybrid micro- and nanomaterials increased the activity of cefotaxime against Staphylococcus aureus. ZSM-5 increased the activity of cefotaxime and ceftriaxone and Fe(3)O(4)/C(12) that of ceftriaxone against Pseudomonas aeruginosa and S. aureus. The anti-Pseudomonas, anti-Klebsiella pneumoniae and anti-Bacillus subtilis activity of cefoperazone was increased by Fe(3)O(4)/C(12) nanoparticles, while the ZSM-5 improved its anti-Escherichia coli, K. pneumoniae, S. aureus and B. subtilis activity, whereas Fe(3)O(4)/PEG(600) against K. pneumoniae. The anti-K. pneumoniae activity of cefepime was increased by all tested nanoparticles, whereas its anti-B. subtilis and anti-E. coli activity was improved by Fe(3)O(4)/C(12) and Fe(3)O(4)/PEG(600) nanoparticles. In conclusion, both magnetic Fe(3)O(4) nanoparticles, charged outside as extra-shell with the antibiotic as well as ZSM-5 microparticles carrying the antibiotic inside the pores, significantly and specifically improved cephalosporin efficacy. A probable explanation for the increase in the antibiotic efficiency is the better penetration through the cellular wall of the antibiotic charged nanoparticles.

Canadian Multicenter Susceptibility Study, with a focus on cephalosporins, from 15 Canadian medical centers. The Canadian Multicenter Study Group.

We have previously reported on the in vitro susceptibilities of 4,482 microorganisms to 10 antimicrobial agents tested as part of a Canadian multicenter study. We now report on the remaining 10 agents tested in that study. Of the cephalosporins reported here, ceftriaxone had the greatest activity (82 to 100% susceptible isolates) against Enterobacteriaceae, compared to ceftizoxime (78 to 100%) and cefoperazone (78 to 100%). Cefoperazone activity against Pseudomonas aeruginosa was 87%, compared to 92% for ticarcillin-clavulanate. All agents had 97% or greater activity against Staphylococcus aureus.

Efficacy of cefoperazone in combination with sulbactam in experimental Staphylococcus aureus endocarditis in rabbits.

The activity of cefoperazone with and without sulbactam was studied in vitro and in vivo against strains of methicillin-resistant and methicillin-susceptible Staphylococcus aureus. Cefoperazone with or without sulbactam was inactive in vitro against the methicillin-resistant strain and was bound by penicillin-binding protein 2a with an IC50 of 190 mg/L (the concentration that reduced radio-labelling with 3H-penicillin by 50%). Cefoperazone was hydrolysed by beta-lactamase in vitro but sulbactam improved cefoperazone activity in a rabbit model of aortic valve endocarditis caused by a beta-lactamase producing methicillin-susceptible strain.

The effect of liposomal cefoperazone against Pseudomonas aeruginosa in a granulocytopenic mouse model of acute lung infection.

The therapeutic efficacy of liposomal cefoperazone against Pseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containing P. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge with P. aeruginosa (75% vs. 38% survival, p = 0.031). Finally, P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic against P. aeruginosa in a granulocytopenic host.

The rapid emergence of fluoroquinolone-methicillin-resistant Staphylococcus aureus infections in a community hospital : An in vitro look at alternative antimicrobial agents

The introduction of ciprofloxacin on an unrestricted basis into a 900-bed community hospital resulted in the emergence of high-level fluoroquinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) during the subsequent 18 months. Susceptibility testing revealed several old and new compounds to which all the S. aureus strains were susceptible. When an MRSA strain became resistant to ciprofloxacin it also exhibited high-level resistance to ofloxacin, fleroxacin, norfloxacin, and enoxacin. Two new experimental fluoroquinolones, WIN 57273 and CI-960, exhibited good activity against all test strains. Among the glycopeptide compounds, mupirocin and teicoplanin were approximately fourfold more active than vancomycin and ramoplanin. Rifampin and trimethoprim-sulfamethoxazole (TMP/SMZ) showed good activity against most strains as did imipenem. For clindamycin, gentamicin, and tetracycline susceptibilities exhibited a bimodal distribution with at least 10% of strains having resistant MIC values. Surprisingly, the addition of sulbactam potentiated the activity of ampicillin against the ciprofloxacin-resistant MRSA strains, however, sulbactam had little effect on cefoperazone activity against these same strains. Time-kill kinetic studies of selected antimicrobials against ciprofloxacin-resistant strains indicated good killing by vancomycin, ampicillin-sulbactam, and TMP/SMZ. Teicoplanin was less bactericidal than vancomycin while these same strains rapidly developed resistance to rifampin even at concentrations 8 × MIC. These data indicate certain alternative compounds within our study warrant further investigation, especially in vivo, against multiply-resistant staphylococci.

Antibacterial activity of cefoperazone and cefoperazone plus sulbactam in a neutropenic site model

Efficacy of cefoperazone versus cefoperazone plus sulbactam was studied in a rabbit neutropenic site infection model against a broad range of clinical isolates including six isolates each of staphylococci, enterococci, pneumococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Therapy of cefoperazone plus sulbactam demonstrated enhanced efficacy against the staphylococci, pseudomonads, and Enterobacteriaceae. The activity of cefoperazone against enterococci and pneumococci was not enhanced or inhibited by the addition of sulbactam. Increased concentrations of cefoperazone found at the infection sites when sulbactam was added to the therapeutic regimen indicates that sulbactam provided a protection to cefoperazone from beta-lactamases produced by staphylococci and Enterobacteriaceae. The combination improved the efficacy of cefoperazone in this animal model.

In vitro activities of cefoperazone and sulbactam singly and in combination against cefoperazone-resistant members of the family Enterobacteriaceae and nonfermenters

Among 28,000 isolates of the family Enterobacteriaceae and nonfermenters isolated at multiple medical centers, 1,084 (4%) were resistant to cefoperazone (MIC, greater than or equal to 64 micrograms/ml) and 1,711 (6%) exhibited cefoperazone MICs of 2 to 32 micrograms/ml. Ninety-six percent of these 2,795 isolates produced beta-lactamase, as determined by the nitrocefin test. Sulbactam alone (8 micrograms/ml) was inactive against 99.6% of the isolates other than Acinetobacter calcoaceticus and Pseudomonas cepacia. Sulbactam enhanced the activity of cefoperazone against 56% of the isolates of the family Enterobacteriaceae and 44% of the nonfermenters. In the presence of sulbactam concentrations of less than or equal to 8 micrograms/ml, 65% of the cefoperazone-resistant isolates had reductions in cefoperazone MICs of greater than or equal to 2 log2 dilution steps and were susceptible to less than or equal to 32 micrograms/ml. Antagonism was not observed.

In vitro activity of cefoperazone/sulbactam and other antimicrobials against anaerobic bacteria

Sulbactam inhibits the hydrolytic activity of several, clinically important β-lactamases including those produced by anaerobic bacteria. This study was undertaken to determine the effect of sulbactam on the activity of cefoperazone against 250 anaerobic bacteria including 174 isolates belonging to the Bacteroides fragilis group and to compare the activity of cefoperazone/sulbactam with other antimicrobial agents. β-lactamase activity was detected in 98% of the isolates of the Bacteroides fragilis group but not in the other species evaluated. Antagonistic activity between cefoperazone and sulbactam was not observed with any of the species. Forty-two percent of the isolates belonging to the B. fragilis group were resistant to cefoperazone. Ninety-four percent of these were converted to either the susceptible or moderately susceptible range upon the addition of sulbactam. Sixty-seven percent were susceptible to the combination cefoperazone/sulbactam and 27% were moderately susceptible. Overall, metronidazole and chloramphenicol were the most active antimicrobials. Significant differences in the antimicrobial susceptibility patterns of members of the B. fragilis group were observed. Sulbactam demonstrated some intrinsic activity against all of the species tested.

Antimicrobial activity of cefoperazone with clavulamic acid or sulbactam against Enterobacteriaceae

Antimicrobial activity of cefoperazone with clavulamic acid or sulbactam against Enterobacteriaceae

Comparative in vitro activity of cefoperazone and various combinations of cefoperazone/sulbactam

Cefoperazone with 2 and 4 μg/ml of sulbactam and in a 2:1 ratio was tested against 1258 clinical isolates of Gram-positive and Gram-negative bacteria, as well as against Gram-negative bacilli that had stably derepressed Type I β-lactamase or that were hyperproductive of non-Type I β-lactamases. The 2:1 cefoperazone/sulbactam combination was the most potent combination tested. With this combination cefoperazone minimum inhibitory concentrations (MICs) of 27 of 40 (67%) of the clinical isolates of Pseudomonas species and 64 of 67 (95%) of clinical isolates of the Enterobacteriaceae were reduced from ⩾64 μg/ml by at least two-fold. In contrast, cefoperazone MICs of ⩾64 μg/ml remained unchanged for 26 (65%) and 24 (60%) of Pseudomonas species and 35 (52%) and 30 (45%) of the Enterobacteriaceae in the presence of 2 and 4 μg/ml of sulbactam, respectively. Cefoperazone/sulbactam in the 2:1 ratio was also the most active combination against the mutants derepressed for Type I β-lactamase. Although the 2:1 combination of cefoperazone/sulbactam had the greatest potency in vitro, it remains to be seen whether this combination is predictive of clinical outcome from treatment of cefoperazone-resistant Gram-negative bacilli with cefoperazone/sulbactam

Comparative activity of newer antibiotics against gram-negative bacilli

The in vitro activities of cefoperazone, cefotaxime, ceftriaxone, ceftazidime, azlocillin, mezlocillin, piperacillin, ticarcillin/clavulanate, aztreonam, imipenem, and ciprofloxacin were concurrently determined against over 1,000 isolates of gram-negative bacilli from clinical specimens of patients at the Cleveland Clinic. Cephalosporins, penicillins, and aztreonam were active against species of Enterobacteriaceae other than Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae. Ceftazidime was the most active cephalosporin against Pseudomonas aeruginosa. Against the Enterobacteriaceae, the rank order of activity of penicillins was ticarcillin/clavulanate greater than piperacillin greater than mezlocillin greater than azlocillin. Against P. aeruginosa, the rank order of activity of penicillins was piperacillin greater than ticarcillin/clavulanate greater than azlocillin greater than mezlocillin. Aztreonam was less active v P. aeruginosa than ceftazidime, cefoperazone, or piperacillin. The most active antimicrobials against all isolates tested were imipenem and ciprofloxacin.

Effect of beta-lactamase inhibitors on the antimicrobial activity of cefoperazone, cefotaxime, and ceftizoxime against aerobic and anaerobic beta-lactamase producing bacteria.

Clavulanic acid (2.0 micrograms/ml) lowered the minimal inhibitory concentrations (MICs) of ceftizoxime and cefotaxime against 49 strains of the Bacteroides fragilis group by a mean of 4.0 and 3.4 log2 concentrations, respectively. Sulbactam plus ceftizoxime gave almost identical results. Sulbactam lowered cefoperazone MICs by a mean of 2 log2 concentrations. Against 52 aerobic and facultative isolates producing a variety of beta-lactamase types, the use of beta-lactamase inhibitors (sulbactam) was most effective in reducing the MICs of cefoperazone.