brl-28500 and Osteomyelitis

Sulbactam (SB) and clavulanic acid (CA) are irreversible inhibitors of the beta-lactamases in the Richmond and Sykes classes II-VI. When combined with ampicillin and ticarcillin, SB and CA, respectively, extend the spectrum of activity of these penicillins to include some beta-lactamase-producing aerobes (Enterobacteriaceae, Hemophilus influenzae, staphylococci) and anaerobes (Bacteroides fragilis group) which would otherwise be resistant. Neither effectively inhibits the class I beta-lactamases frequently produced by Pseudomonas aeruginosa, Enterobacter, and Serratia, in part explaining the resistance observed with these organisms. Clinically, both agents were as effective as the comparative therapies in all but two of the trials reviewed. Given the current data, the decision to add these agents to the formulary should be based on hospital resistance patterns and on the cost of these antimicrobials in comparison to conventional therapies.

Topics: Ampicillin; Arthritis, Infectious; Bacterial Infections; Bacteroides fragilis; beta-Lactamase Inhibitors; Clavulanic Acids; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Osteomyelitis; Pelvic Inflammatory Disease; Respiratory Tract Infections; Sulbactam; 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

A 4-year-old girl with Legg-Calve Perthes' disease and immunoglobin G1 subclass deficiency developed osteomyelitis of the proximal femur and septic arthritis of the hip secondary to Haemophilus influenzae, type f. This microorganism is a rare cause of invasive infections in children, primarily of the central nervous system (CNS) and respiratory track. It has not previously been associated with bone and joint infections.

Topics: Arthritis, Infectious; Ceftriaxone; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Femur; Haemophilus Infections; Haemophilus influenzae; Hip Joint; Humans; Osteomyelitis; 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

Timentin is an exciting new antibiotic agent that is a combination of ticarcillin and clavulanic acid. Forty-seven patients with osteomyelitis received 3.1 g of Timentin intravenously every six hours. The mean duration of therapy was 32 days. The diagnosis was made by bone biopsy; bone biopsy was repeated at the completion of therapy. The bacterial etiology was predominately gram-positive organisms. Of the organisms isolated, Staphylococcus aureus was the most common isolate and represented 39 percent of the total isolates. Streptococcus species were isolated in 13 percent, Group D Enterococcus in 15 percent, Pseudomonas aeruginosa in 10 percent; 23 percent of the isolates were other gram-negative organisms. All but one organism were initially sensitive to Timentin. Three resistant organisms were isolated during therapy. Twenty-seven patients were classified as having a cure, based on no growth on repeat bone biopsy cultures and clinical signs of bone healing. Twenty-two patients returned for follow-up (one to nine months after therapy) and had no evidence of infection; however, because of the short follow-up period, these patients were classified as showing improvement. Six patients had adverse reactions to Timentin: two had mild allergic phenomena and two had prolonged bleeding times. In all four, therapy was discontinued. Two patients had a transient, mild elevation in the level of serum glutamic-pyruvic transaminase (less than twice normal levels). This new agent looks exciting for therapy of both gram-positive and gram-negative bacterial osteomyelitis.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Osteomyelitis; Penicillins; Ticarcillin

Timentin, a combination of clavulanic acid (0.1 g) and ticarcillin (3.0 g), has proved effective in vitro against bacterial pathogens that produce beta-lactamases. The usual etiologic bacteria of osteochondritis of the foot (Pseudomonas species) and osteomyelitis/septic arthritis (Staphylococcus aureus) are commonly resistant to penicillins. To date, we have used Timentin to treat 30 children with bone, joint, and deep soft tissue infections. Timentin was administered intravenously at an average dosage of 207 mg/kg per day for mild to moderate infection and 310 mg/kg per day for bone and joint infections with systemic signs (sepsis). The lower dose was used in 24 patients and the other six patients, who had signs of sepsis, received the higher dose. All patients received Timentin intravenously over 30 minutes every four to six hours for a minimum of five days (mean 6.6 +/- 2.6 days, range five to 14 days). The mean time to defervescence and/or reduction in clinical symptoms was 1.6 +/- 1.3 days (range zero to four days). Osteochondritis due to P. aeruginosa was diagnosed in six patients, and septic bursitis, osteomyelitis, or septic arthritis due to S. aureus (13 patients) or Staphylococcus species and group A streptococci (four patients) was diagnosed in 17 patients. All isolates were susceptible to Timentin in vitro by disk-diffusion analysis. All patients showed a response to therapy with Timentin, with or without surgical intervention. All patients had clinical and microbiologic cures; no adverse reactions or side effects were observed. There have been no clinical or microbiologic relapses to date. Timentin may prove to be useful in specific bone and joint infections in children.

Topics: Arthritis, Infectious; Bacterial Infections; Bone Diseases; Cellulitis; Child; Child, Preschool; Clavulanic Acids; Drug Combinations; Female; Humans; Joint Diseases; Male; Osteochondritis; Osteomyelitis; Penicillins; Prospective Studies; Ticarcillin