brl-28500 and Staphylococcal-Infections

Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6-44 days) and gestational age of 25 weeks (23-28 weeks). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043-0.075]) compared with a PNA ≥14-45 days (0.078 L/kg/h [0.047-0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14 days) or q8h (PNA ≥ 14-45 days) achieved the target exposure for organisms with a minimum inhibitory concentration ≤16 μ/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 μg/mL), increased dosing frequency or extended infusion are necessary.

Topics: beta-Lactamase Inhibitors; Clavulanic Acids; Computer Simulation; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Male; Microbial Sensitivity Tests; Models, Biological; Prospective Studies; Staphylococcal Infections; Staphylococcus; Ticarcillin

Initial antibiotic treatment of extracavitary arterial graft infections is usually empiric or based on Gram's stain findings. Increasing virulence of bacteria causing extracavitary arterial graft infections may render previous choices of antibiotics obsolete. The purposes of this study were to correlate Gram's stain findings of gram-positive bacteria and gram-negative bacteria with wound cultures and provide a microbiologic basis for appropriate initial antibiotic therapy.. Between July 1, 1979 and June 30, 1994, specimens obtained on the day of admission from purulent wounds involving 113 extracavitary arterial graft infections were retrospectively reviewed for Gram's stain and culture and sensitivity results.. Gram's stain findings correlated with final cultures on only 28 of 113 cases (25%), including 20 of 48 pure gram-positive, 2 of 24 pure gram-negative, and 6 of 41 mixed bacterial cultures. Staphylococcus aureus was the most common gram-positive bacteria cultured (43 isolates) and Pseudomonas species was the most common gram-negative bacteria (25 isolates). Bacteria were sensitive to a first-generation cephalosporin in only 32% (36 of 113) of infections. A combination of vancomycin and either ticarcillin-clavulanic acid or ceftazidime, which have minimal toxicity and provide excellent coverage against staphylococci, Pseudomonas, and other gram-negative bacteria, would have covered 96% (109) and 95% (107) of cultured organisms, respectively.. Regardless of Gram's stain findings, current recommendations for initial treatment of extracavitary arterial graft infections should include vancomycin and ceftazidime or ticarcillin-clavulanic acid until final culture and sensitivity results dictate the use of more selective antibiotics.

Topics: Anti-Bacterial Agents; Arteries; Blood Vessel Prosthesis; Ceftazidime; Clavulanic Acids; Drug Therapy, Combination; Humans; Pseudomonas Infections; Retrospective Studies; Staphylococcal Infections; Surgical Wound Infection; Ticarcillin; Transplantation, Autologous; Vancomycin; Veins

Multicenter trials of ticarcillin/potassium clavulanate (Timentin) for bone, joint, skin and soft tissue infections in children were performed from 1983 to 1986. Fifty children with culture-confirmed Staphylococcus aureus infections were identified. Sixteen children (ages 6.2 +/- 3.9 years) with bone and joint infections received Timentin for 8.7 +/- 2.4 days with 11 of 16 cures, 5 of 16 improved, 11 of 11 bacteriologic cures and 3.9 +/- 3.5 days of fever. Thirty-two children (ages 5.7 +/- 3.5 years) with skin and soft tissue infections received Timentin for 5.3 +/- 1.6 days with 22 of 32 cures, 10 of 32 improved, 32 of 32 bacteriologic cures and 1.4 +/- 1.3 days of fever. Three patients had S. aureus bacteremia; all were clinical and bacteriologic cures. All S. aureus isolates were susceptible to Timentin, 18 of 23 isolates tested produced beta-lactamase and 21 of 44 isolates tested were resistant to ticarcillin. The purpose of this report is to describe the clinical efficacy of Timentin in treating these types of S. aureus infections in children.

Topics: Child; Child, Preschool; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Infant; Multicenter Studies as Topic; Penicillins; Staphylococcal Infections; Ticarcillin

Staphylococcus aureus bacteremia has long been known to cause significant morbidity and mortality. The optimal treatment of this disease has evolved over the years. Recently, criteria have been established for the use of shorter courses of antibiotic therapy in certain patients, most notably those with an easily removed source of the bacteremia. We present the case of a 55-year-old man with S aureus bacteremia unrelated to an intravascular device. He was treated with "short-course" antibiotic therapy, and lumbar diskitis and an epidural abscess developed.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; Cefazolin; Cephalosporins; Clavulanic Acids; Discitis; Drug Therapy, Combination; Enzyme Inhibitors; Epidural Abscess; Follow-Up Studies; Foot Diseases; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteomyelitis; Staphylococcal Infections; Staphylococcus aureus; Ticarcillin; Vancomycin

The efficacy of ticarcillin-clavulanic acid was compared with the efficacies of standard antistaphylococcal agents (flucloxacillin, oxacillin, nafcillin, and vancomycin) and ticarcillin in an experimental model of Staphylococcus aureus endocarditis. Therapy was either initiated soon (8 h) after infection, when numbers of bacteria in aortic valve vegetations were relatively low (approximately 6 to 8 log10 CFU/g), or delayed until 24 h after infection, when the vegetations usually contained greater than 9 log10 CFU/g. Doses of the antibiotic were selected to produce peak concentrations in rat serum similar to those achievable in humans after administration of parenteral therapeutic doses. Ticarcillin-clavulanic acid was more effective overall than ticarcillin alone against endocarditis caused by beta-lactamase-producing strains of S. aureus, illustrating the beta-lactamase-inhibitory activity of clavulanic acid in vivo. Ticarcillin-clavulanic acid was as effective as the standard antistaphylococcal beta-lactam agents flucloxacillin, oxacillin, and nafcillin in these infections, whereas vancomycin was generally less active. These results illustrate the clinical potential of ticarcillin-clavulanic acid in the prophylaxis or therapy of severe staphylococcal infections.

Topics: Animals; beta-Lactamase Inhibitors; beta-Lactamases; Clavulanic Acids; Drug Therapy, Combination; Endocarditis, Bacterial; Male; Microbial Sensitivity Tests; Rats; Staphylococcal Infections; Staphylococcus aureus; Ticarcillin

Osteomyelitis is becoming a more common infection. This increase has been associated with an increase in the number of orthopaedic surgical procedures and with severe bone trauma. The etiology of osteomyelitis is also changing, with more gram-negative and more polymicrobial infections due to both gram-positive and gram-negative pathogens. Underlying diseases such as diabetes mellitus, peripheral vascular and sickle cell disease are associated with a poor cure rate when treated with antibiotics. The emergence of resistant strains of bacteria during the long-term treatment necessary for osteomyelitis has been documented, and continues to be a concern, as are the other side effects.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Ceftazidime; Clavulanic Acids; Drug Combinations; Humans; Osteomyelitis; Staphylococcal Infections; Ticarcillin

Topics: Amoxicillin; beta-Lactamase Inhibitors; Blister; Clavulanic Acid; Clavulanic Acids; Drug Therapy, Combination; Humans; Kinetics; Models, Theoretical; Penicillins; Staphylococcal Infections; Staphylococcus aureus; Ticarcillin