Teicoplanin in the treatment of bone and joint infections: An open study.

Osteomyelitis and septic arthritis caused by Gram-positive pathogens may require prolonged inpatient treatment. The glycopeptide antibiotic, teicoplanin, can be administered once daily to outpatients, and was assessed in a multicenter, open trial in patients with such infections. Patients with proven Gram-positive osteomyelitis or septic arthritis were treated with once-daily teicoplanin, 6-12 mg/kg per day, after three loading doses at intervals of 12 h, for 4-6 weeks. A total of 342 patients were recruited, of whom 220 were fully evaluable. Surgical procedures were performed in 82% of patients. Clinical success by the end of treatment was recorded in 81/90 patients (90%) with acute osteomyelitis, 70/79 patients (88.6%) with chronic osteomyelitis, and 42/51 patients (82.4%) with septic arthritis. Four patients with acute and 4 with chronic osteomyelitis and 5 patients with septic arthritis failed to respond to treatment. Relapse was known to have occurred in 10 patients with osteomyelitis and 4 with septic arthritis. Mean trough levels of teicoplanin reached during the first week of therapy were 10 mg/l (mean dose, 6 mg/kg) and 21 mg/l (mean dose, 12 mg/kg). A mean of 75% of the treatment course was given at home. One or more adverse events were reported in 166/342 patients (48.5%), 119 (34.8%) of which were thought to be related to teicoplanin, and treatment was discontinued in 59 patients. Fever, chills, and rashes were the most common side-effects, but were usually mild. Teicoplanin was shown to be a cost-effective method of treatment of bone and joint infections caused by multiple-resistant Gram-positive pathogens.

The use of oral antibiotics in lower-extremity infections.

It is estimated that American podiatrists write 78,000 prescriptions per week for oral antibiotics. This article discusses the currently available oral antibiotics and their appropriate usage in podiatric medicine.

Bone and soft-tissue infections of the lower extremity in diabetics.

The foot is the most common site of infection in the diabetic individual, and one of every four diabetics eventually seeks medical care for a foot problem. This article examines pathologic conditions of the lower extremity from a variety of views, including pathophysiology, classification, microbiology, infections, osteomyelitis, treatment, and prevention strategies.

Teicoplanin in the treatment of bone and joint infections. Teicoplanin Bone and Joint Cooperative Study Group, USA.

Teicoplanin is a new glycopeptide antibiotic with activity against Gram-positive bacteria, including methicillin-resistant organisms. Teicoplanin is administered once daily, either intravenously or intramuscularly. Teicoplanin was given once daily, intravenously or intramuscularly, in the treatment of hospitalized or ambulatory patients with Gram-positive bone or joint infections. A total of 90/98 patients were evaluated for efficacy; 41 had acute osteomyelitis, 41 had chronic osteomyelitis, and 8 had septic arthritis. At the end of therapy, 37 acute osteomyelitis patients were cured/improved with a 90% cure rate at 6-month follow-up; 2 relapsed and 1 failed. At the end of therapy 30 chronic osteomyelitis patients were cured/improved with an 88% cure rate at 6-month follow-up; 2 relapsed and 1 failed. 100% of the septic arthritis patients were cured at the end of therapy and at 1-month follow-up. The most common bacterial isolates cultured from bone were S. aureus (39 isolates), S. epidermidis (11 isolates), other coagulase-negative staphylococci (20 isolates), enterococci (6 isolates), and other streptococcal species (20 isolates). The most common bacterial isolates cultured from joint fluid were S. aureus (6 isolates) and S. epidermidis (2 isolates). All patients tolerated the intramuscular or intravenous routes of administration well. Adverse reactions were mild and most cases did not require discontinuation of therapy. The majority of therapy was administered on an outpatient basis. Teicoplanin was safe, effective, convenient and relatively well tolerated in patients with acute or chronic osteomyelitis or septic arthritis.

Use of ciprofloxacin in podiatric medicine.

Ciprofloxacin is the first of the new class of antibiotics known as fluoroquinolones to be approved for use in skin, skin structure, and bone and joint infections. It has an extremely broad spectrum and is particularly effective against traditionally resistant gram-negative rods. As an oral agent, it is as effective as parenteral drugs against a variety of organisms and diseases. Its spectrum, pharmacokinetics, and podiatric indications are reviewed.

A multicenter comparative study of cefotetan once daily and cefoxitin thrice daily for the treatment of infections of the skin and superficial soft tissue.

To compare the effectiveness of cefotetan administered at 2 g once a day with cefoxitin at 1 or 2 g three times a day in the treatment of hospitalized patients with skin and superficial soft tissue infections, 194 patients from eight centers were enrolled in an open, randomized trial. Most of the 104 evaluable patients in the cefotetan group and 50 in the cefoxitin group were young men with community-acquired, moderate or severe cellulitis, or abscesses of the upper and lower extremities caused by Staphylococcus aureus, Streptococcus species, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and other species of bacteroides, peptococcus species, and peptostreptococcus species. The mean duration of treatment was 7.5 days for cefotetan and 7.1 days for cefoxitin. A successful clinical response was achieved in 97 percent of the cefotetan patients and in 94 percent of the cefoxitin patients. Of the 88 and 39 bacteriologically evaluable patients in the cefotetan and cefoxitin groups, respectively, a satisfactory bacteriologic response occurred in 96 percent and 87 percent of the patients. No clinically significant changes in clinical laboratory determinations were noted. The incidence of adverse reactions in the cefotetan group (17 percent) was significantly different from that for the cefoxitin group (6 percent) (p less than 0.05); however, the incidence of treatment-related reactions was not significant and the events were mild. Discontinuation of therapy was necessary only in two patients in whom allergic-type reactions developed. A once-daily regimen of cefotetan was as effective as thrice-daily cefoxitin in this study in the treatment of primarily polymicrobial, moderate, or severe infections of the skin and superficial soft tissue.

Results of noncomparative studies of cefotetan in the treatment of obstetric and gynecologic infections.

In a multicenter trial involving 11 centers, 160 women were enrolled to evaluate the safety and effectiveness of 1 or 2 gm of cefotetan administered every 12 hours in the treatment of obstetric and gynecologic infections. The 133 evaluable patients generally were under 25 years of age, were nonwhite, and had hospital-acquired endometritis or pelvic inflammatory disease caused by both aerobic and anaerobic bacteria. Escherichia coli, Neisseria gonorrhoeae, group D streptococci, Bacteroides sp., and Peptococcus sp. were among the most frequently isolated pathogens. The patients were treated for a mean of 5.6 +/- 1.6 days and received a total dose of 19.27 gm. The signs and symptoms of infection were cleared or improved in 93% of the 133 patients evaluable for clinical response. Of the 116 evaluated bacteriologically, 95% had a satisfactory or presumed satisfactory response; only six patients (5%) were considered to be bacteriologic failures. Differences in the results of several clinical laboratory tests performed before and after treatment were statistically, but not clinically, significant (p less than 0.05). Safety was evaluated in the 158 patients who received cefotetan, and only four (3%) had adverse reactions considered related to the drug. Cefotetan was clearly effective and produced no untoward reactions in these women with obstetric and gynecologic infections caused by both aerobic and anaerobic organisms when administered at 1 or 2 gm every 12 hours.

Efficacy and safety of aztreonam in the treatment of serious gram-negative bacterial infections.

Aztreonam was used in the initial treatment of infection of the urinary tract (23 cases), respiratory tract (17 cases), skin and soft tissue (12 cases), abdominal cavity (three cases), endocarditis (two cases), septicemia (eight cases), and osteomyelitis (two cases). In 26 of 60 evaluable infectious episodes, aztreonam was used alone. Clinical cure was observed in 35 of 60, improvement in 24 of 60, and failure in one of 60 cases. Ten patients developed subsequent superinfection. Aztreonam was well tolerated, although one case of exfoliative dermatitis and one of pseudomembranous colitis occurred. However, these cases were complicated by proximal administration of other antibiotics.

Infections complicating puncture wounds of the foot.

Pedal puncture wounds are a relatively common injury seen predominantly during the warm weather months and in children. Although most of these injuries heal completely with no sequelae, up to 10% may become infected and produce late complications. Of these, osteomyelitis caused by P. aeruginosa is the most devastating, and it may progress to bone destruction that will require extensive surgical debridement. If instituted early, adequate primary care usually provides the best chance of prevention of these infections.

Cefotetan pharmacokinetics in volunteers with various degrees of renal function.

Twenty-six volunteers with various degrees of renal function were given a single 1-g dose of cefotetan intravenously over 30 min. Concentrations of cefotetan and cefotetan tautomer in plasma and urine were determined by high-performance liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated according to a two-compartment open model. The mean plasma cefotetan concentration at the end of the intravenous infusion did not vary with renal function and ranged between 122 and 126 micrograms/ml. The mean terminal half-life was 4.2 h in normal volunteers and 9.9 h in volunteers with moderate renal impairment. There was a significant linear correlation between the systemic clearance of cefotetan and creatinine clearance. The cumulative amount of cefotetan excreted in the urine over 24 h in normal volunteers was approximately 49% of the dose, but this was reduced in volunteers with moderate renal impairment. The mean urinary cefotetan concentrations generally peaked during the 2- to 4-h interval after dosing. Cefotetan tautomer was sporadically detected in the plasma and urine of approximately 50% of the volunteers. The mean plasma cefotetan tautomer concentrations and mean total cumulative urinary recoveries of cefotetan tautomer were only minimal compared with those for cefotetan. The mean percentage of the dose excreted in the urine as cefotetan tautomer was not significantly affected by the degree of renal impairment. Recommendations for the dosing of cefotetan in renal-impaired patients are given.

In vitro activity of A-56619 and A56620, two new aryl-fluoroquinolone antimicrobial agents.

The in vitro antimicrobial activity of two new aryl-fluoroquinolone antibiotics, A-56619 and A-56620, was compared with those of norfloxacin and several other antibiotics against 448 bacterial isolates. A-56620 was the most active agent tested. The usual 90% MIC of A-56620 was less than or equal to 2 micrograms/ml, except for enterococci, gentamicin-resistant Serratia marcescens, and gentamicin-resistant Pseudomonas aeruginosa, for which the 90% MIC was 4 micrograms/ml. A-56619 and norfloxacin were generally severalfold less active than A-56620. Cross resistance was observed between the quinolone antibiotics and other unrelated antibiotic classes.

Comparative in vitro antimicrobial activity of carumonam, a new monocyclic beta-lactam.

The antimicrobial activity of carumonam (formerly RO-17-2301), a monocyclic beta-lactam antibiotic, was compared with those of aztreonam, cefotaxime, cefoperazone, ceftazidime, piperacillin, and gentamicin against 455 bacterial isolates. Carumonam did not possess activity against gram-positive cocci and was generally comparable to aztreonam and ceftazidime for most gram-negative bacilli. However, carumonam was the most active beta-lactam against gentamicin-resistant Pseudomonas aeruginosa strains (90% MIC, 8 micrograms/ml).