Posttraumatic Aeromonas hydrophila osteomyelitis.

Aeromonas hydrophila is a gram-negative organism that is the causative agent in several clinical infections. Although it has been reported to cause osteomyelitis in immunocompromised patients, it has not been reported to cause this in the normal host. We describe two patients in whom acute osteomyelitis developed following trauma in freshwater lakes. Cultures yielded A hydrophila, and both patients responded to a two-week course of parenteral antibiotics followed by oral tetracycline hydrochloride in the outpatient setting. Since A hydrophila is a common inhabitant of freshwater lakes, it should be suspected in infections occurring in this epidemiologic setting.

Toxicity of amphotericin B plus flucytosine in 194 patients with cryptococcal meningitis.

A multicenter prospective randomized trial of four versus six weeks of amphotericin B, 0.3 mg/kg per day, plus flucytosine, 150 mg/kg per day, was performed with 194 patients with cryptococcal meningitis. One or more toxic drug reactions developed in 103 patients: azotemia (51), renal tubular acidosis (two), leukopenia (30), thrombocytopenia (22), diarrhea (26), nausea/vomiting (10), and hepatitis (13). The four- and six-week regimens were complicated by toxicity in 44 percent and 43 percent of cases, respectively. Toxicity appeared during the first two weeks of therapy in 56 percent and during the first four weeks in 87 percent. Azotemia did not occur more frequently in renal transplant recipients or diabetic patients. Cytopenias did not appear more often in patients with hematologic malignancies or those receiving immunosuppressive therapies. Toxic reactions that contributed to death developed in five patients (two with azotemia, one with pancytopenia, one with hepatitis, one with ileus). Amphotericin B-induced azotemia was not a significant risk factor for the subsequent development of bone marrow, gastrointestinal, or hepatic toxicity attributable to flucytosine. Flucytosine toxicity was associated with peak serum flucytosine levels of 100 micrograms/ml or more during two or more weeks of therapy (p = 0.005). Peak 5-fluorouracil levels were not predictive of toxicity. An initial dose of flucytosine is recommended based on the creatinine clearance: 150 mg/kg per day at a creatinine clearance above 50 ml/minute, 75 mg/kg per day at a creatinine clearance of 26 to 50 ml/minute, and 37 mg/kg per day at a creatinine clearance of 13 to 25 ml/minute. The serum creatinine level should be monitored twice weekly and the creatinine clearance weekly during therapy in order to anticipate changes in serum flucytosine concentration. In addition, it is recommended that the serum flucytosine level be determined two hours after an oral dose once a week, and that the dose be adjusted to maintain a level of 50 to 100 micrograms/ml.

Giant cell arteritis presenting as interstitial lung disease.

A 58-year-old woman had a clinical history compatible with polymyalgia rheumatica but with an unexplained interstitial lung disease. Evaluation, including biopsy specimens of temporal artery, lung, and gastrocnemius muscle, was consistent with giant cell arteritis. This case identifies giant cell arteritis as a cause of interstitial lung disease.

Invasive pulmonary aspergillosis in nonimmunocompromised, nonneutropenic hosts.

Invasive pulmonary aspergillosis occurs predominantly in individuals who are neutropenic or who have severe defects in cell-mediated immunity. The isolation of Aspergillus from respiratory secretions of normal hosts usually signifies tracheobronchial colonization, not disease. Recent experience with three nonimmunocompromised patients who had invasive pulmonary aspergillosis, each of whom had Aspergillus isolated from respiratory secretions early in his illness, led to a reassessment of the significance of the isolation of Aspergillus from tracheobronchial secretions. Two of 10 nonimmunocompromised, nonleukopenic individuals who had pulmonary infiltrates and whose sputum yielded Aspergillus had invasive pulmonary aspergillosis, whereas two of five individuals who had pulmonary infiltrates and whose bronchial washings grew Aspergillus had invasive disease. These findings indicate that invasive pulmonary aspergillosis should be considered when Aspergillus is isolated from the respiratory secretions of anyone who has pneumonia, regardless of host defense status.

Role of newer antimicrobial agents in the treatment of mixed aerobic and anaerobic infections.

Mixed infections with aerobic and anaerobic bacteria are being recognized with increasing frequency in clinical practice. Several concepts regarding such infections are clinically significant for the physician. These include the presence and significance of species in the Bacteroides fragilis group at clinical sites of infection, the facilitation of B. fragilis virulence by beta-lactamase producing aerobic bacteria and the role of enterococci in such infections. In response to the need for new forms of therapy for mixed aerobic and anaerobic infections, several new classes of antimicrobial agents have been introduced. Some of these allow for the potential option of monotherapy in certain clinical settings. In addition to clinical and microbiologic efficacy, safety and cost-effectiveness are factors that must be addressed with regard to these agents.

Interaction of cefotaxime and aminoglycosides against enterococci in vitro.

The antibacterial activities of cefotaxime, gentamicin, tobramycin, and amikacin as well as the combinations of cefotaxime and aminoglycosides were tested against 50 strains of enterococci. Synergy studies were performed by the time-kill method, and with this technique the combination of cefotaxime plus gentamicin appeared to be more active than the combination of cefotaxime plus tobramycin or cefotaxime plus amikacin. Results of this in vitro study suggest cefotaxime and gentamicin may provide some activity against enterococci, although not sufficient to substitute for proven therapy such as penicillin-ampicillin and gentamicin.

Blastomycosis: pulmonary and pleural manifestations.

Seven diverse cases of pulmonary blastomycosis were recently diagnosed at this institution. It is our purpose to review the unique features in the spectrum of this systemic illness as illustrated by these cases. The wide range of radiographic findings included parenchymal disease, mass-like lesions, and pleural effusions. One patient had endobronchial blastomycosis. Although significant pleural effusions have been uncommonly reported, we note this finding in two of our seven cases. Both of these patients had thoracentesis, which yielded markedly elevated pleural fluid total protein. These seven cases emphasize the marked variability of pulmonary and pleural blastomycosis.

Interactions of clindamycin with antibacterial defenses of the lung.

Clindamycin is speculated to have select advantages in the treatment of certain infections because biologically active antibiotic is internalized by macrophages and PMNs in vitro. By challenging pulmonary host defenses with various bacterial species as probes, we were able to evaluate clindamycin-phagocyte interaction in vivo. A murine model was developed using an implanted mini-osmotic pump to maintain constant clindamycin blood levels at 1/4 MIC (1 microgram/ml). Mice pretreated for 24 h with clindamycin killed a significantly greater percentage of intratracheally inoculated Bacteroides thetaiotaomicron in 4 h than did control animals (37 +/- 2% versus 7 +/- 5%). The enhancing effects of clindamycin on pulmonary defenses could not be duplicated by a 1-h preincubation of B. theta in 1/4 MIC of clindamycin before inoculation into untreated mice. Clindamycin blood levels of 1 microgram/ml did not alter the rate at which Pseudomonas aeruginosa (clindamycin-resistant) was killed by pulmonary defenses, suggesting that clindamycin did not cause nonspecific activation of phagocytic defenses. Both PMNs and alveolar macrophages lavaged from the lungs of clindamycin-treated mice contained bioassayable concentrated intracellular antibiotic. The presence of intracellular antibiotic was further supported by experiments in which the intrapulmonary killing of large numbers of Staphylococcus aureus (sensitive, but not resistant organisms) was significantly enhanced (89 +/- 5 versus 70 +/- 5%) by clindamycin pretreatment. In contrast, phagocytes lavaged from mice with constant 1/4 MIC (4 micrograms/ml) blood levels of penicillin G had no detectable intracellular antibiotic activity and did not augment the intrapulmonary killing of B. theta.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated serum D-arabinitol levels in patients with sarcoidosis.

D-Arabinitol has been found in the serum of patients with candidiasis in an incidence varying from 38 to 82%. While screening serum by gas chromatography for the presence of this sugar, we observed elevated concentrations in several patients with sarcoidosis. In an attempt to determine the significance of this chance observation, we tested serum from additional patients with sarcoidosis along with serum from patients with other clinical conditions known to be associated with elevated D-arabinitol levels. Of 53 patients with sarcoidosis, 27 (51%) had elevated concentrations of this compound. Only one of these patients had decreased renal function (creatinine, 2.5 mg/dl). We were unable to correlate elevated values with extent of the disease. Although the significance of this finding is not clear, it may represent a clue to the pathogenesis of sarcoidosis.