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The effects of three beta-lactamase inhibitors: YTR830H, sulbactam and clavulanic acid on the growth of human cells in culture.

Three beta-lactamase inhibitors: YTR83OH (YTR), sulbactam and clavulanic acid were studied for their effects on the growth of human amnion FL line cells. The numbers of viable cells after the 3-day culture were almost unaffected by YTR at concentrations up to 250 mg/l. The effects of sulbactam on FL cells were similar to those of YTR. The growth inhibitory effects of clavulanic acid were significantly different and were effective down to a concentration of 50 mg/l. The morphological effects were also observed microscopically.

Cell Division↗

The role of Pseudomonas species in patients treated with ampicillin and Sulbactam for gangrenous and perforated appendicitis.

A prospective, randomized, double-blinded comparison of Sulbactam and ampicillin and clindamycin and gentamicin is described. The combination of ampicillin and Sulbactam was not as effective in the management of perforated appendicitis and gangrenous appendicitis as was clindamycin and gentamicin. While both combinations of antibiotics had good anaerobic activity and failures were not associated with the recovery of Bacteroides fragilis group organisms, infectious complications were seen in patients from whom Pseudomonas were isolated. These pseudomonads were not nosocomially acquired and were found especially in patients with perforated appendicitis. We concluded that the combination of clindamycin and gentamicin, although less convenient to administer to the patient, remains the adjunctive antibiotic management of choice for perforated or gangrenous appendicitis. The epidemiologic factors of Pseudomonas species as a primary pathogen in peritonitis deserves further attention.

Adult↗

[A clinical trial with ampicillin and sulbactam in various infections].

Eighty four patients with various infections were treated with parenteral ampicillin and sulbactam. Twenty seven patients had meningitis five septic arthritis and osteomyelitis, two systemic salmonellosis, nine intrathoracic infections, five of which were complicated with pleural empyema; thirty patients had infection of the deep tissues of the neck, and the remaining eleven had soft tissue infection in different localizations. The clinical and microbiological results were interpreted together and the overall rate of success in treatment with ampicillin and sulbactam was found to be 98.8%.

Adolescent↗

Comparative therapeutic results of penicillin plus chloramphenicol versus ampicillin plus sulbactam in childhood meningococcemia.

Fifty-seven cases of meningococcemia were evaluated retrospectively. The age of the patients ranged between 2 and 17 years. Of the 57 patients investigated for the efficacy of antibiotic treatment, 31 (54.4%) were treated with benzylpenicillin plus chloramphenicol and 26 (45.6%) with ampicillin plus sulbactam. Patients with criteria for a poor prognosis (presence of disseminated intravascular coagulation, low arterial blood pressure, and altered consciousness) were divided equally into two treatment groups. There were no statistically significant differences between the two treatment groups except for the higher incidence of convulsion in the group given penicillin plus chloramphenicol. The mortality rate was 19.3 percent for patients treated with benzylpenicillin plus chloramphenicol and 7.6 percent for patients treated with ampicillin plus sulbactam (p = 0.19; overall mortality rate 14%).

Adolescent↗

In vitro activity of cefoperazone-sulbactam: Singapore experience.

In vitro activity of commonly used antimicrobial agents against consecutively isolated 521 strains of Gram negative bacilli causing serious infections in the National University Hospital, Singapore were tested in parallel with cefoperazone-sulbactam combination. With the combination complete resistance of 2% and intermediate resistance of 5% were noted among the 521 strains tested. Resistance to imipenem was low (5%) but resistance against other antimicrobial agents varied from 12% (amikacin) to 80% (ampicillin). In vitro data demonstrated a possible future role for cefoperazone-sulbactam in the treatment of sepsis caused by Gram negative bacilli in our hospital.

Anti-Bacterial Agents↗

Effect of imipenem and sulbactam on sessile cells of Acinetobacter baumannii growing in biofilm.

The effect of the age of biofilms formed by Acinetobacter baumannii on the activity of sulbactam and imipenem on sessile cells was investigated. Against cells of young biofilms both antibiotics were rapidly bactericidal. As the biofilm aged, sulbactam lost most of its activity, but imipenem continued to be bactericidal to some extent. This fact probably reflects the ability of imipenem to exert bactericidal activity on slow-growing bacteria.

Acinetobacter↗

Correlation of in vitro susceptibility testing results for amoxicillin-clavulanate and ampicillin-sulbactam using a panel of beta-lactamase-producing Enterobacteriaceae.

Correlation between in vitro susceptibility results for amoxicillin-clavulanate (AMC) and ampicillin-sulbactam (SAM) was studied using 136 clinical and control strains of Enterobacteriaceae harboring TEM-1, SHV-1 or OXA-1-like beta-lactamases. Determination of minimal inhibitory concentration of antibiotics was performed by agar dilution. The beta-lactamases were initially characterized using isoelectric focusing. Further identification was done by DNA hybridization with or without prior PCR amplification. All strains sensitive to SAM were found to be sensitive also to AMC. In contrast, among those susceptible to AMC, only 50% were sensitive to SAM while 36% gave intermediate results and 14% were resistant. Major differences were found solely among SHV-producers while minor differences occurred mostly among TEM-producers. This phenomenon is probably related to the differential activities of clavulanate and sulbactam against various beta-lactamases. In conclusion, testing of Enterobacteriaceae isolates for susceptibility to AMC and SAM should be performed and reported individually to avoid erroneous designation of susceptibility.

Amoxicillin-Potassium Clavulanate Combination↗

Comparison of the post-antibiotic effect (PAE) induced by ceftizoxime, ceftriaxone, cefoxitin, ampicillin-sulbactam, and ticarcillin-clavulanate against selected isolates of Bacteroides fragilis and B. thetaiotaomicron.

The exposure of bacteria to various groups of antimicrobials at different concentrations can produce damage to the bacteria that persists even after removal of the antimicrobial agent. The post antibiotic effect (PAE) of beta-lactams on aerobic gram-negative bacilli is relatively short (<1 h), however, little information is available regarding anaerobic gram-negative bacilli. We studied the PAE of ceftizoxime, ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, and ceftriaxone against strains of Bacteroides fragilis and B. thetaiotaomicron at antimicrobial concentrations 4x, 8x, and 16x the MIC values using colony count determinations of treated and untreated cultures. Against B. fragilis H931, ceftizoxime-induced PAE values were 2 h, 3 h 24 min, and 11 h 36 min at 4xMIC, 8xMIC, and 16xMIC while for the B. thetaiotaomicron isolates PAEs ranged from 2 h 27 min to 6 h 12 min at the same concentrations. Cefoxitin PAE values were 3 h 6 min and 2 h 18 min for the clinical isolates at 16xMIC and 3 h 24 min and 1 h 12 min against the laboratory strains at 16xMIC respectively, and for ceftriaxone 1 h 12 min and 5 h 12 min, respectively, for the B. thetaiotaomicron D933 and B. fragilis H931 strains at 16xMIC. With ampicillin-sulbactam, the longest PAE values were observed at 16xMIC with all the test isolates of B. fragilis and B. thetaiotaomicron. PAE values induced by ticarcillin-clavulanate overall were the shortest for the two clinical isolates. These studies indicate substantial PAE values for beta-lactams against selected anaerobes which may be an important factor in the dosing regimen of these test agents.

Journal Article↗

Amoxicillin-sulbactam: A clinical and therapeutic review.

Combinations of beta-lactamase inhibitors with penicillins, especially aminopenicillins, have broad-spectrum antibacterial activity against most of the common pathogens of the respiratory and urinary tracts. This means that they are an ideal treatment for infections such as otitis media, sinusitis, special cases of pharyngeal tonsillitis (recurring forms, indirect pathogenic action, or after the failure of amoxicillin monotherapy), acute exacerbations of chronic bronchitis, cystitis, urethritis, etc. The amoxicillin-sulbactam combination is active against both beta-lactamase producer and nonproducer strains, and is effective against Gram-positive cocci (Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus of nonhospital origin), Gram-negative cocci (Neisseria gonorrhoeae, Moraxella catarrhalis and others), Gram-negative bacilli (nonhospital strains of Haemophilus influenzae, Escherichia coli and Klebsiella pneumoniae and others) and anaerobes. Its antimicrobial activity means that it is indicated in the treatment of respiratory, ear, nose and throat, urinary, dermatological and gynecological infections caused by susceptible germs, as well as in a variety of surgical situations (both as a treatment and as prophylaxis). It is absorbed very well orally, and its pharmacokinetic profile is very favorable, with very good tissue penetration. It is reasonably well tolerated: in a variable percentage of cases it may cause modification of intestinal transit and/or fecal consistency, which usually abates spontaneously. The new formulation for administration at intervals of 12 h is easier to use, is better tolerated and favors completion of therapy. In summary, the amoxicillin-sulbactam combination is effective and well tolerated in most infections of nonhospital origin in adults and children. (c) 2001 Prous Science. All rights reserved.

Journal Article↗

[Comparative in vitro activity ampicillin, cefoperazone, their combinations with sulbactam, as well as that of other antibiotics against aerobic gram-negative microorganisms].

The activity of 12 antibiotics against 849 strains of gram-negative aerobes isolated in special and general hospitals of Moscow and Smolensk in 1992-1993 was assayed with the method of serial microdilutions. By the criteria of the activity (percentage of the susceptible strains by the NSSLS criteria) against the isolates the antibiotics were arranged as follows: ciprofloxacin (89.8 per cent) > imipenem (89.6 per cent) > cefoperazone + sulbactam (86.1 per cent) > amikacin (83.8 per cent) > ceftazidime (81.8 per cent) > ceftriaxone (71.1 per cent) > cefoperazone (70.9 per cent) > cefotaxime (70.9 per cent) > gentamicin (60.8 per cent) > ampicillin + sulbactam (44.7 per cent) > cefazolin (37.5 per cent) > ampicillin (23.0 per cent). The frequency of the antibiotic susceptible isolates in the special hospitals was lower at the average by 20 per cent than that in the general hospitals with respect to all the antibiotics assayed.

Ampicillin↗

Sulbactam-cefoperazone polyhydroxybutyrate-co-hydroxyvalerate (PHBV) local antibiotic delivery system: in vivo effectiveness and biocompatibility in the treatment of implant-related experimental osteomyelitis.

In this study, a novel antibiotic carrier system for use in the treatment of implant-related and chronic osteomyelitis was developed. Sulbactam-cefoperazone was introduced to rods of polyhydroxybutyrate-co-hydroxyvalerate (22 mol % HV, w/w), a member of a family of microbial-origin polymer that is biodegradable, biocompatible, and osteoconductive due to its piezoelectric property. The antibiotic-loaded carrier was implanted into the infection site that was induced by Staphylococcus aureus inoculation into the rabbit tibia. The effectiveness of this was assessed macroscopically, radiographically, bacteriologically, and histopathologically. Findings of infection subsided on day 15 and almost complete remission was observed on day 30. The control side that contained antibiotic-free rods, however, worsened. These findings prompted us to conclude that the novel biodegradable antibiotic carrier developed in the present study seems to be a promising candidate for use in the treatment of severe bone infection.

Animals↗

Efficacy of sulbactam in an in vitro model of mixed aerobic/anaerobic infections.

Bacterial interactions in mixed infections may interfere with antimicrobial therapy. The in-vitro efficacy of ampicillin alone, combination sulbactam/ampicillin, and metronidazole was studied. Strains of Bacteroides fragilis, Escherichia coli, and Enterococcus faecalis, alone and in association, were tested by means of a broth dilution method. Minimal bactericidal concentrations (MBC) of ampicillin for B. fragilis 74 in association with E. coli 68 were up to 16-fold higher than for B. fragilis 74 alone (256 compared to 16 mg/l), but only 2-fold higher for sulbactam (5 mg/l)/ampicillin (0.5 and 0.25 g/l). Association of B. fragilis 45 and E. faecalis 186 increased ampicillin MBC of E. faecalis 186 from 2 to 16 mg/l, but the combination sulbactam/ampicillin restored activity of ampicillin. In association with E. faecalis, metronidazole MBCs of B. fragilis increased up to 64-fold. Strains of E. faecalis and E. coli were able to destroy 10 mg/l metronidazole within 8 to 20 h. The present experiments demonstrated effectiveness of sulbactam/ampicillin to inhibit beta-lactamases of associated pathogens. Destruction of metronidazole by E. faecalis lends additional support to the use of the combination in aerobic/anaerobic infections including E. faecalis.

Ampicillin↗

Relative efficacy of tazobactam, sulbactam and clavulanic acid in enhancing the potency of ampicillin against clinical isolates of Enterobacteriaceae.

Three beta-lactamase inhibitors were combined with ampicillin in a fixed 2:1 ratio. The activity of ampicillin was enhanced by tazobactam and by clavulanic acid, and to a lesser extent by sulbactam when tested against fresh clinical isolates of Enterobacteriaceae. At a concentration of 8 micrograms/ml, ampicillin alone inhibited 49.6% of 2,434 consecutive isolates of enteric bacilli compared to 81% inhibited by ampicillin combined with tazobactam or clavulanic acid and 69.3% inhibited by the sulbactam/ampicillin combination. A four-fold or greater reduction in ampicillin MICs was observed in comparable numbers of isolates with all three combinations, but the most marked effects were seen with strains that were highly resistant to ampicillin.

Ampicillin↗

[Ampicillin and sulbactam concentrations in the irradiated mandible after oral squamous cell cancer].

INTRODUCTION: Radiation therapy of the oral and maxillo-facial region increases the risk of an infected osteoradionecrosis (IORN) which is a severe complication. Therefore, perioperative antibiotics for the prophylaxis of ORN is a standard in clinical oncology. The combination therapy of ampicillin and sulbactam (Unacid) promises a good therapeutic and prophylactic outcome. PATIENTS: We compared the concentration of Unacid in bone and blood specimens of 22 irradiated patients. All patients were irradiated with 39.6 Gy prior to surgery. The specimens were obtained during the operation 3 weeks after the end of the radiation therapy. RESULTS: The concentration of ampicillin/sulbactam in the blood was 124.9/64.5 microg/ml. The bone specimens showed a concentration of ampicillin/sulbactam of 5.54/1.21 microg/g. The concentration of the antibiotic in the bone was three to four times lower than in non-irradiated patients. Nevertheless, this concentration exceeds the minimum inhibitory concentration for bacteria in the oral cavity such as streptcoccae (MHK90<0.25 microg/ml) or staphylococcae (MHK90=0.12-2.0 microg/ml). CONCLUSIONS: The results of this study suggest, that Unacid is an effective antibiotic in the prophylaxis of ORN in irradiated patients with head and neck tumors.

Adult↗

A comparison of ampicillin plus sulbactam versus clindamycin and gentamicin for treatment of postpartum infection.

Thirty-six hospitalized patients, 18 in each of two groups, with postpartum upper genital tract infection were enrolled in a randomized, prospective study comparing treatment with sulbactam/ampicillin, to treatment with clindamycin/gentamicin. One (5.5%) clinical failure was reported in each group. Side effects were minimal in both groups and did not warrant discontinuation of treatment. The in vitro activity of ampicillin versus sulbactam/ampicillin (1:2) was evaluated and these data were compared with data from other drugs commonly used for aerobic and anaerobic infections. Sulbactam eliminated resistance to ampicillin in all anaerobic and most aerobic isolates.

Adult↗

A bacteriological assessment of ampicillin with sulbactam as antibiotic prophylaxis in patients undergoing biliary tract operations. The West of Scotland Surgical Infection Study Group.

A prospective audit of 644 patients undergoing biliary tract operations has been conducted in ten district general hospitals. All patients received a single dose of ampicillin 2 g and sulbactam 1 g as antibiotic prophylaxis. Bacteria were cultured from the bile of 121 patients. In patients with sterile bile the incidence of postoperative infection was 2.5%, while in those with colonized bile it was 22% (P less than 0.0001). The 35 patients from whose bile bacteria of two or more species were isolated, had a higher incidence of wound infection (34%) than those whose bile yielded only one species of bacterium (17%; P less than 0.05). Seventeen of the 27 patients with colonized bile who developed postoperative infection were shown to be infected by the same organisms that had been isolated from their bile. The patients whose bile yielded organisms resistant to the prophylactic antibiotic combination did not have a significantly higher rate of infection than those from whose bile only sensitive organisms were obtained. A marked difference in sensitivity patterns between the participating hospitals was observed.

Adolescent↗

Sulbactam: secondary mechanisms of action.

Light and scanning electron microscopy showed that 0.25, 0.5 and 1 times the minimum inhibitory concentrations (MICs) of sulbactam (SULB) caused filament formation in different species of Enterobacteriaceae, while 2 and 4 times the MICs caused spheroplast formation and subsequent lysis. By using a competitive assay with 125I-penicillin X, SULB showed a primary affinity for the PBP 1a and PBP3 of Escherichia coli, as well as for the PBP1a of Proteus mirabilis. The bactericidal interaction of human polymorphonuclear leukocytes (PMN) and SULB against E. coli K-1 resistant to the bactericidal activity of human serum was studied in vitro; however, SULB concentrations showed variations in the medium according to human kinetic data. Under these conditions, bacterial growth occurred in Hanks balanced salt solution containing SULB, PMN, or SULB-PMN in combination. In addition, bactericidal activity was observed in serum, with a killing rate of 90% for PMN or SULB, and 95% for SULB-PMN in combination. The postantibiotic enhancement of PMN bactericidal function was assessed against E. coli K1 pretreated with 0.5 the MIC of SULB (32 micrograms/ml) for 0.5 hr. The 90% bacterial killing rate of PMN occurred by 1.5 hr for pretreated bacteria and by 2.5 hr for untreated bacteria. Furthermore, the luminol-enhanced chemiluminescence (CL) assay using an E. coli stimulus showed that SULB does not modify PMN activity.

Blood Bactericidal Activity↗

In vitro activity of ampicillin, amoxicillin, ampicillin-sulbactam, and amoxicillin-clavulanic acid against consecutive clinical isolates of Enterobacteriaceae.

Ampicillin was generally twice as active as amoxicillin against 2440 consecutive isolates of Enterobacteriaceae from five medical centers. When beta-lactamase inhibitors were added to the penicillins, there was a significant increase in susceptibility. The magnitude of the increased susceptibility to ampicillin-sulbactam (A-S) and amoxicillin-clavulanic (A-C) acid varied with the species and types of beta-lactamases elaborated. Although cross-susceptibility and cross-resistance between ampicillin and amoxicillin was nearly complete, major differences were documented between A-S and A-C with 6.7% of our consecutive isolates of Enterobacteriaceae. The clinical significance of these findings remains uncertain, but they may help explain some of the discrepancies occasionally observed by clinical microbiologists with the combination drugs.

Amoxicillin↗