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Cefonicid is a new second-generation cephalosporin that has broad-spectrum antibacterial activity, achieves high peak serum concentrations, and has a long half-life. The high serum concentration and long half-life of cefonicid make it feasible to administer the drug once daily either intravenously or intramuscularly. For the treatment of bacterial osteomyelitis, a specific antibacterial agent is administered for four to eight weeks. Ideally, the optimal antibiotic should have good activity against organisms commonly implicated in bone infections, be easy to administer, be stable in inflammatory conditions, achieve good concentrations in bone, and have minimal toxicity. For treatment of Staphylococcus aureus endocarditis, the same criterion of minimal toxicity should be met for the agent used; in addition, it should have excellent antistaphylococcal activity in vivo and in vitro, be stable to beta-lactamase, and exhibit good bactericidal activity at trough serum levels. In uncomplicated Neisseria gonorrhoeae infections, the ideal antibiotic should be one that could be administered in a single dose in a small volume and would not be painful on intramuscular injection. The antibiotic should be nontoxic; stable to N. gonorrhoeae beta-lactamase; and reliably able to eradicate urethral, endocervical, rectal, and pharyngeal infections. Cefonicid may fulfill some of these criteria.

Although hyperbaric oxygen (HBO) is as effective as cephalothin against osteomyelitis due to Staphylococcus aureus in the rabbit, the effect is not by directing killing. To investigate the mechanism, argon washouts (perfusion) and oxygen tensions were measured by intramedullary probes placed in the metaphyses of infected and uninfected tibias. In vitro phagocytic killing activity for S. aureus was determined at oxygen tensions found in these bones under ambient and HBO conditions. Mean tibial oxygen tensions (mm Hg) under ambient conditions were 21 (infected) and 45 (uninfected); under HBO conditions, 104 (infected) and 321 (uninfected). Perfusion was decreased in osteomyelitic bone and was not acutely increased by HBO in either normal or infected bone. Phagocytic killing of S. aureus was markedly decreased at 23 mm Hg of O2, significantly improved at 45 and 109 mm Hg, and most effective at 150 mm Hg. Thus, in osteomyelitic bone, HBO increased intramedullary oxygen to tensions consistent with normal phagocytic function.

The effectiveness of parenteral cefotaxime in the treatment of adults with acute septic arthritis or acute or chronic osteomyelitis was evaluated in a multicenter trial. The drug was given to 47 patients admitted to the University of Texas Medical Branch Hospitals or Hahnemann Medical College and Hospital (UT-H study) and to 40 patients in other medical centers using an identical protocol. In the UT-H study, cefotaxime was effective in 15 of 16 patients (94%) with acute osteomyelitis, in 24 of 27 patients (89%) with chronic osteomyelitis, and in four of four patients (100%) with acute septic arthritis. In the multicenter study, the success rates were as follows: acute osteomyelitis, six of six (100%); chronic osteomyelitis, 14 of 19 (74%); and septic arthritis, 12 of 15 (80%). The antibiotic was well tolerated in most patients. The most serious side effect was significant neutropenia, which occurred in three patients. Cefotaxime appears to be a clinically useful, broad-spectrum antibiotic for bone and joint infections.

Hyperbaric oxygen (HBO) is used as adjunctive therapy of chronic osteomyelitis, but its efficacy remains controversial. A recently developed rabbit model for osteomyelitis due to Staphylococcus aureus was used to compare the results of treatment with HBO, cephalothin, a combination of both, or no treatment. Cultures of bone were positive in 10 (91%) of 11 control animals (untreated), five (36%) of 14 animals treated with HBO, eight (47%) of 17 treated with cephalothin, and six (40%) of 15 treated with HBO plus cephalothin. All three treatment groups differed significantly from untreated controls in the number of positive cultures obtained (P less than 0.01), but there were no significant differences among treatment groups. In vitro growth and killing curves (1.0 microgram of cephalothin/ml) constructed after exposure to HBO revealed no change from parallel control studies in ambient air. These data demonstrate that therapy with HBO is at least as effective as antibiotic therapy. The therapeutic effectiveness of HBO does not appear to be related to antibacterial activity.

Cefotaxime, a new cephalosporin, was evaluated for efficacy and safety in the treatment of 52 patients with serious bone and joint infections. For five of these patients therapy could not be evaluated. Diagnosis of osteomyelitis or septic arthritis was made on the basis of clinical and roentgenographic evidence of infection. The diagnosis of a bone infection was confirmed by either a positive culture of a bone biopsy or of blood in combination with a positive bone scan or roentgenogram. The diagnosis of a joint infection was confirmed by a positive culture of joint aspirate samples. Osteomyelitis was arrested in 93% (15 of 16 patients) of cases of acute osteomyelitis, 89% (24 of 27 patients) of cases of chronic osteomyelitis, and 100% (4 of 4 patients) of cases of septic arthritis. Follow-up ranged from 0-17 months after completion of cefotaxime therapy. Laboratory monitoring revealed positive direct Coombs' test (six patients), neutropenia less than 1,000 polymorphonuclear leukocytes (two patients), macular rash (two patients), phlebitis (two patients), and pseudomembranous colitis (one patient). It is concluded that cefotaxime is a useful and safe antibiotic for the treatment of osteomyelitis and septic arthritis.