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Fifteen patients who had severe Staphylococcus aureus infections were treated with minocycline for 6 to 24 days; all responded satisfactorily. Where possible, posttherapy cultures were taken, and in all instances, the pathogen was eradicated. There was no adverse reactions. Minocycline proved to be an acceptable and effective alternative for staphylococcal soft-tissue infections. It has the following advantages: (1) it is administered orally on a twice-daily dosage schedule, which facilitates patient compliance; (2) its toxicity is well defined and is not troublesome during short-term therapy; and (3) it penetrates tissues in therapeutic amounts and yields serum levels that are well above the minimum inhibitory concentrations of most staphylococci.

24 patients with severe infections were treated with intravenous minocycline 100 mg every 12 hours. Average blood levels were within therapeutic ranges during the first 12 hours after the initial dose. Determination of efficacy of therapy in 23 of the patients who were evaluable showed that clinical and bacteriological results were satisfactory in 20 patients, unsatisfactory in 2, and questionable in 1. One patient developed a fatal secondary infection which may have been related to prior therapy with minocycline. No toxicities or side-effects were observed.

Aspergillus is a ubiquitous saprophytic fungus seldom pathogenic for normal hosts. Aspergillus osteomyelitis occurs infrequently and is typically limited to patients with predisposing factors, including leukocyte dysfunction, malignancy with neutropenia, steroid or antibiotic therapy, pulmonary aspergillosis, and surgical manipulation. The spine is most frequently affected, and the clinical presentation is nonspecific (50% afebrile). Diagnosis requires demonstration of characteristic, acutely branching, broad, septate hyphae in biopsy material, and culture of Aspergillus. Therapy includes debridement of necrotic bone and loculated purulence combined with amphotericin B and possibly 5-fluorocytosine or rifampin.

Minocycline was added to normal and hyperlipemic serum samples in concentrations of 1 approximately 10 mcg/ml. These specimens had similar protein contents. Chemically extractable minocycline was quantitated fluorometrically. Hyperlipemic serum (cholesterol 480 mg/100 ml; triglycerides 321 mg/100 ml) yielded an average of 50% less minocycline than did normal serum (cholesterol 170 mg/100 ml; triglycerides 114 mg/100 ml). When ultrafiltrates of serum containing 6, 12 and 20 mcg/ml minocycline were assayed microbiologically, it was evident that variations in serum triglyceride and cholesterol levels did not alter the ratio of bound to free drug. Minocycline appears to be reversibly associated with, and/or soluble in, triglyceride-cholesterol components of serum.

Percentages of free and protein-bound cefazolin and cephaloridine in serum and interstitial fluid of dogs were determined by ultrafiltration and microbiologic assay. The percentages of cephaloridine and cefazolin bound to protein in serum were 10% and 80%, respectively. In interstitial fluid accumulating within tissue-embedded polypropylene capsules, 29% of cefazolin was bound to protein, and cephaloridine was unbound. Both antibiotics rapidly penetrated the interstitial fluid and attained measurable levels 5 min after intravenous administration. Levels of total cefazolin in the interstitial fluid were generally higher than those of cephaloridine; however, concentrations of free cephaloridine in the fluid exceeded the levels of free cefazolin after the first 15 min. Binding of anitbiotics by serum proteins does not restrict such agents to the intravascular space, since a highly protein-bound compound has been shown to penetrate interstitial fluid as readily as one that is minimally bound. It should be noted, however, that this penetration may be due primarily to the slow rate of binding of cefazolin to serum proteins.

Cefazolin is a semi-synthetic derivative of cephalosporin C that has a lower cross-immunogenicity with penicillins than do the other cephalosporins. This agent was evaluated as an alternative to penicillin in the therapy of patients with pneumococcal pneumonia. Thirty patient were treated with cefazolin, most receiving 125 or 250 mg IM every 12 hours for 5-10 days. Satisfactory clinical responses were obtained in 29 of these 30 patients, and none complained of pain following IM injections. Three patients developed eosinophilia while receiving cefazolin, and one of these also had a maculopapular eruption that may have been an allergic reaction to cefazolin. Serum levels of cefazolin were measured at 1, 6, and 12 hours after administration. Susceptibilities of 100 isolates of Streptococcus pneumoniae, including these patients' organisms, were determined by broth dilution. Both cefazolin and cephalothin were bactericidal for all 100 isolates at concentrations of 2 microgram/ml or less. Cefazolin appears to be an entirely adequate alternative to penicillin for the therapy of pneumococcalpneumonia. This agent is effective in low dosages, and adequate serum levels are maintained for long periods of time, permitting twice-daily administration.

This study in dogs using tissue-implanted capsules indicates that cephalothin, cefazolin, ampicillin and tetracycline are excreted in the bile, appearing in this fluid at concentrations greater than the concomitant serum levels. Hepatic interstitial fluid concentrations of these agents differed little from levels achieved in soft tissues elsewhere in the body, indicating that compounds which are concentrated in bile do not necessarily achieve high levels in the hepatic parenchyma. The selection of an antimicrobial agent for the therapy of hepatic parenchymal infection or obstructive cholecystitis should, therefore, be based on susceptibilities of the suspected organism rather than on the relative tendencies of various agents to be concentrated in bile.

Infective endocarditis is the most common condition predisposing a patient to splenic abscess, and the conditions of 37 such patients are reviewed herein. Streptococci accounted for 18 abscesses, with six containing enterococci; 12 other contained staphylococci. Symptoms suggesting splenic abscess include abdominal distention, hiccups, and pain in the left flank, abdomen, and shoulder. Physical signs include recurrent or persistent fever and abdominal tenderness, with splenomegaly often inapparent. The most frequent finding on x-ray film is pleural effusion on the left side. Seventeen patients not undergoing splenectomy died; in these, the diagnosis of splenic abscess was established postmortem. Twenty patients underwent splenectomy, 19 of whom received antibiotics and survived; one patient who was not treated with antibiotics died. Physicians should suspect splenic abscess in patients with endocarditis, particularly those with staphylococcal or enterococcal endocarditis. Those patients with clinical evidence suggestive of splenic abscess should undergo specific diagnostic studies, and exploratory laparotomy may be necessary.