Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid (original) (raw)

Continuous infusion of ticarcillin–clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics

International Journal of Antimicrobial Agents, 2005

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of ␤-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis , cellulitis , pulmonary infections , febrile neutropenia , vascular infections , intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Clinical Isolates of <i>Staphylococcus aureus</i> Show Variation in <i>β</i>-Lactamase Production and Are More Susceptible to Antibiotics Conjugated with <i>β</i>-Lactamase Inhibitors

Open Journal of Medical Microbiology, 2016

β-Lactam antibiotics are a cornerstone in the treatment of bacterial infections on account of its high therapeutic index and selective toxicity-they act by inhibiting the biosynthesis of peptidoglycan, a key component in bacterial cell wall. Ninety (90) clinical specimens obtained from the microbiology unit Specialist Hospital Bauchi were screened for S. aureus, positive isolates were examined for β-Lactamase expression by using two Penicillin G concentrations (5000 IU/ml and 25,000 IU/ml) in acidometric agar technique with phenol red as indicator, and the susceptibility pattern of the isolates to β-Lactam antibiotics was also determined. S. aureus prevalence of 31% (28/90) was obtained, of which 96% (27/28) of strains were β-Lactamase positive in the standard test, while 63% (17/27) were able to hydrolyze penicillin G concentration of 25,000 IU/ml (5X the concentration in the standard test), and a strain was found to be β-Lactamase negative. The resistance to five β-Lactams, ampicillin, cephalexin, amoxicillin, cloxacillin and flucloxaillin, were 100%, 96%, 89%, 74% and 56% respectively. When ampicillin and amoxicillin were conjugated to β-Lactamase inhibitors sulbactam and clavulanic acid respectively the resistance to ampicillin decreased to 21% and to amoxicillin to 15%. The antibiotic susceptibility profile revealed β-Lactamase elaboration to be the major mechanism of resistance to the β-Lactams. β-Lactam utilization as therapeutic option would thus require the search for sensitive irreversible β-Lactamase inhibitors for the β-Lactamase enzymes or agents to block the release of β-Lactamase by strains.

A multicentre study:Staphylococcus andEnterococcus susceptibility to antibiotics

European Journal of Epidemiology, 1994

A multicentre study to evaluate the susceptibility of Gram-positive cocci isolated from clinical samples, was performed by six centres working in different areas of Italy. We examined 4,544 strains of Staphylococcus aureus, 4,381 strains of coagulase-negative staphylococci and 2,478 strains of enterococci. The following antibiotics were tested: penicillin G, ampicillin, amoxicillin, piperacillin, imipenem, oxacillin, ofloxacin, pefloxacin, ciproftoxacin, gentamicin, tobramycin, amikacin, netilmicin, rifampicin, clindamycin, tetracycline, cotrimoxazole, erythromycin, chloramphenicol, vancomycin and teicoplanin. Oxacillin-susceptible staphylococci confirmed their susceptibility to many other anti-microbial agents while oxacillin-resistant strains confirmed their multiple and frequent resistance to antibiotics. Resistance to oxacillin, cotrimoxazole and chloramphenicol was more frequent in coagulase-negative staphylococci than in Staphylococcus aureus. Aminoglycosides, rifampicin and quinolones were more active against coagulase-negative staphylococci than against Staphylococcus aureus. Enterococci were susceptible to penicillins and imipenem, and moderately susceptible to ciprofloxacin. Susceptibility of 70-79% was observed with high levels of aminoglycosides. Excellent results against staphylococci and enterococci were observed with vancomycin and teicoplanin.

The role of β-lactam/β-lactamase inhibitors in the management of mixed infections

International Journal of Antimicrobial Agents, 1999

Microbiological studies show that the in vitro antimicrobial activity of sulbactam -ampicillin encompasses not only Gram-positive and Gram-negative aerobes, but also anaerobes. Such a broad spectrum of activity suggests its suitability as monotherapy for the empiric management of polymicrobial infections. Typical mixed infections, which are frequently life-threatening, include those occurring in the abdomen or pelvis, diabetic foot infections, and brain abscess. Numerous comparative clinical studies have revealed the clinical and bacteriological efficacy of sulbactam -ampicillin to be comparable to that of imipenem -cilastatin and the second-generation cephalosporins cefoxitin and cefotetan. In addition, other studies have demonstrated that sulbactam -ampicillin monotherapy is cost-beneficial. A reduction in the duration of hospitalization, the lack of potentially toxic side-effects, and lower drug costs associated with monotherapy all contribute to the cost-effectiveness of sulbactam -ampicillin.

Treatment of hospitalized patients with complicated skin and skin structure infections: double-blind, randomized, multicenter study of piperacillin-tazobactam versus ticarcillin-clavulanate. The Piperacillin/Tazobactam Skin and Skin Structure Study Group

Antimicrobial Agents and Chemotherapy, 1993

We compared the efficacy and safety of two beta-lactam-beta-lactamase inhibitor combinations, namely, piperacillin-tazobactam and ticarcillin-clavulanate, in the treatment of complicated bacterial infections of skin that required hospitalization. The study was a randomized, double-blind, comparative trial involving 20 centers. The infections were classified as (i) cellulitis with drainage, (ii) cutaneous abscess, (iii) diabetic or ischemic foot infection, and (iv) infected wounds and ulcers with drainage. The clinical response rates were comparable for the two treatment regimens (61% of the patients were cured with piperacillin-tazobactam and ticarcillin-clavulanate and improvement was seen in 15 and 16% of patients treated with piperacillin-tazobactam and ticarcillin-clavulanate, respectively). Both regimens were found to be safe and well tolerated. These data support the use of piperacillin-tazobactam for initial empiric therapy of hospitalized patients with complicated skin and s...

Comparative in vitro potency of amoxycillin–clavulanic acid and four oral agents against recent North American clinical isolates from a global surveillance study

International Journal of Antimicrobial Agents, 2003

The in vitro activity of amoxycillin Á/clavulanic acid was compared with four comparator oral antimicrobial agents; ampicillin, azithromycin, cefuroxime and trimethoprim Á/sulphamethoxazole against 4536 recent clinical isolates covering 29 species isolated in the US and Canada between 1997 and 1999. Based upon Minimum inhibitory concentrations (MICs), amoxycillin Á/clavulanic acid was the most active agent against many Gram-positive species and phenotypes including methicillin susceptible Staphylococcus aureus (MSSA) Staphylococcus epidermidis , Enterococcus faecalis , Streptococcus pyogenes , Streptococcus pneumoniae including penicillin intermediate and macrolide resistant strains and was as active as ampicillin against Streptococcus agalactiae , penicillin resistant S. pneumoniae and viridans streptococci. Against Enterobacteriaceae amoxycillin Á/clavulanic acid in general, displayed weak activity with only Proteus mirabilis and Proteus vulgaris displaying levels of susceptibility above the 90th percentile. Amoxycillin Á/clavulanic acid had significant activity against many species of Gram-negative non-Enterobacteriaceae including Haemophilus influenzae , Haemophilus parainfluenzae and Moraxella catarrhalis but negligible activity against Burkholderia cepacia , Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Amoxycillin Á/clavulanic acid continues to retain excellent activity against the majority of targeted pathogens despite 20 years of clinical use.

Amoxicillin-clavulanic acid in treatment of urinary tract infection due to gram-negative bacteria resistant to penicillin

Antimicrobial Agents and Chemotherapy, 1981

Twenty-one adult patients with urinary tract infections caused by penicillinresistant bacteria completed treatment with amoxicillin alone or amoxicillin plus clavulanic acid in a randomized double-blind clinical trial. Of the 13 patients treated with amoxicilhin plus clavulanic acid, the absence of bacteriuria within 7 days of therapy was observed in 85%, as compared with only 25% of the 8 patients receiving amoxicillin only. There were no significant side effects nor any clinical, biochemical, or hematological abnormalities related to either treatment. It was concluded that the combination of clavulanic acid and amoxicillin could be useful in the treatment of uncomplicated urinary tract infection caused by penicillinresistant bacteria.