Fluconazole-induced congenital anomalies in three infants.

Fluconazole has been associated with various teratisms in animals, including craniofacial ossification defects, thin, wavy ribs, and renal pelvis defects. We describe three infants born to women who were receiving fluconazole through or beyond the first trimester of pregnancy. All of the infants had congenital anomalies; no other drug was implicated. Only one of the three infants survived. Their anomalies, similar to those observed in animal studies, were largely craniofacial, skeletal (i.e., thin, wavy ribs and ossification defects), and cardiac. One of these infants was previously reported as having Antley-Bixler syndrome; however, given the chronology described herein and the similarity of this infant to the others, we conclude that her deformities also represent the potent teratogenic effect of fluconazole.

Comparison of in vitro susceptibilities of Bacteroides and Fusobacterium species in inland southern California to published patterns as a guide to empiric therapy.

Anaerobic bacteria, particularly the Bacteroides group, are becoming increasingly resistant to antimicrobials. Anaerobic susceptibility testing is often not done routinely in clinical laboratories, causing clinicians to depend on national survey results or susceptibility patterns published by different centers. In this study, we have determined anaerobic susceptibility patterns of 200 clinical isolates of anaerobic gram-negative bacilli from four hospitals in the inland countries of southern California (Inland Empire). Of 11 antibiotics tested, metronidazole and chloramphenicol were the most active, with no resistance noted, followed by imipenem, ticarcillin/clavulanate, and ampicillin/sulbactam. Among cephalosporins, cefoxitin was the most active and cefotetan the least. Significant differences in the susceptibility pattern to cefoxitin were observed in one hospital. Differences between our inland patterns and those for Los Angeles Wadsworth VA Hospital were seen for cefoxitin in the B fragilis group and piperacillin for B fragilis. We confirmed the National Committee for Clinical Laboratory Standards (NCCLS) recommendation for periodic determination of anaerobic susceptibility patterns. We also suggest that clinical laboratories routinely identify anaerobes to the species level to facilitate clinical application of in vitro results.

Life-threatening deep fascial space infections of the head and neck.

In the preantibiotic era, deep fascial space infections were common, and physicians were well acquainted with their complex and sometimes subtle manifestations. Widespread use of antibiotics, however, not only has significantly decreased the incidence of deep neck infections but also has altered their clinical manifestations. This article is designed to emphasize the key clinical manifestations of the several life-threatening deep neck infections and relate them to critically important anatomic structures in the neck.

Tricuspid valve endocarditis due to Staphylococcus aureus. Correlation of two-dimensional echocardiography with clinical outcome.

We studied 53 episodes (51 patients) of tricuspid valvular endocarditis caused by Staphylococcus aureus in a predominantly addicted population and correlated two-dimensional echocardiographic findings with clinical outcome. Thirty-eight episodes with (vs 15 episodes without) tricuspid vegetations on the two-dimensional echocardiogram were significantly associated with (1) longer duration of fever on therapy (mean of 12.3 days vs 6.8 days, respectively; p less than 0.005); and (2) higher frequency of increased right ventricular end-diastolic (RVED) dimension (25 of 38 cases [66 percent] vs two of 15 cases [13 percent], respectively; p less than 0.01). Only patients with increased RVED dimension (5/25; 20 percent) required tricuspid valvular surgery for prolonged fever or progressive right-sided heart failure (p less than 0.05 vs patients with normal RVED dimension). Tricuspid vegetations greater than 1.0 cm identified a subset of patients at increased risk for developing clinical right-sided heart failure during the active or convalescent phase of endocarditis (p less than 0.02 vs patients with tricuspid vegetations less than 1.0 cm). An unexpectedly high prevalence of asymptomatic prolapse of the mitral valve was observed in this population (23 of 53 episodes; 43 percent). Detection of tricuspid vegetations in patients with endocarditis due to S aureus is not a primary indication for early surgery, but identifies patients more likely to exhibit short-term and long-term complications of their infection.

Ciprofloxacin for eradication of methicillin-resistant Staphylococcus aureus colonization.

Ciprofloxacin (750 mg orally twice a day) was used to treat 22 episodes of methicillin-resistant Staphylococcus aureus (MRSA) colonization among 20 patients. Most patients had serious, progressive underlying medical diseases and had multiple sites of colonization. Eleven had previously received parenteral vancomycin therapy. Duration of ciprofloxacin therapy was from seven to 28 days. Therapy was discontinued in eight patients because of minor adverse reactions (two patients) or serious events attributed to underlying diseases (six patients). These serious events included seizures in two patients with known seizure disorders. Of the remaining 14 courses of therapy, 11 (79 percent) were associated with eradication of MRSA colonization. For the 18 patients who received at least two weeks of therapy, results of cultures from 47 of the 56 colonized sites became negative. Recolonization with MRSA occurred in four patients within one month. Increased resistance to ciprofloxacin was observed in seven of the 22 treatment episodes; this was associated with treatment failure in three patients and successful therapy in one patient; therapy was discontinued for other reasons in three patients. For comparison, medical records of 31 patients whose clinical specimens revealed MRSA but who did not receive ciprofloxacin were reviewed. MRSA colonization (as opposed to infection) was not eradicated in any patient who received only a single drug or no specific therapy directed against MRSA; four of seven patients given combination therapy had colonization eradicated. Although there is the potential for increased resistance, ciprofloxacin is an important new option that can be used as a single agent for eradication of MRSA colonization. Additional study is needed to define the optimum use of ciprofloxacin as a single agent and in combination therapy for MRSA colonization and infection.

Efficacy of ciprofloxacin in experimental aortic valve endocarditis caused by a multiply beta-lactam-resistant variant of Pseudomonas aeruginosa stably derepressed for beta-lactamase production.

The emergence of multi-beta-lactam resistance is a limiting factor in treating invasive Pseudomonas infections with newer cephalosporins. The in vivo efficacy of ciprofloxacin, a new carboxy-quinolone, was evaluated in experimental aortic valve endocarditis caused by a strain of Pseudomonas aeruginosa which is stably derepressed for beta-lactamase production and is resistant to ceftazidime and multiple other beta-lactam agents. A total of 51 catheterized rabbits with aortic catheters in place were infected with this strain and then received no therapy (controls), ceftazidime (75 mg/kg per day), or ciprofloxacin (80 mg/kg per day). Ciprofloxacin sterilized all blood cultures and significantly lowered vegetation densities of P. aeruginosa by day 2 of treatment versus controls (P less than 0.0005) and animals receiving ceftazidime (P less than 0.0005). This beneficial effect of ciprofloxacin was also noted on therapy days 6 and 11. Ciprofloxacin rendered most vegetations (85%) culture negative over the 11-day treatment period and achieved bacteriologic cure in 73% of animals (P less than 0.0005 versus other therapy groups). Ciprofloxacin prevented bacteriologic relapse at 6 days posttherapy. No ciprofloxacin resistance was detected among Pseudomonas isolates from cardiac vegetations. Ciprofloxacin warrants further evaluation in vivo versus multi-drug-resistant gram-negative bacillary infections.

Comparative efficacy of ciprofloxacin and ceftriaxone in experimental arthritis caused by Escherichia coli.

Ciprofloxacin was compared with ceftriaxone in a rabbit model of septic arthritis caused by Escherichia coli. Both agents significantly reduced mean E. coli counts in septic joint fluid (P less than 0.0005 versus untreated controls) and also within infected synovial tissue (P less than 0.01 versus controls). Ciprofloxacin regimens caused a higher frequency (P less than 0.05) of synovial tissue sterilization (53%) than did ceftriaxone (25%).

Ciprofloxacin in experimental aortic valve endocarditis due to Pseudomonas aeruginosa.

Left-sided endocarditis caused by Pseudomonas aeruginosa is frequently associated with failure of medical therapy in man. The efficacy of ciprofloxacin and netilmicin + azlocillin has been studied in 79 rabbits with aortic valve endocarditis caused by a serum-resistant strain of P. aeruginosa. Infected animals received either: no therapy; ciprofloxacin (80 mg/kg/day); or netilmicin (6.5 mg/kg/day) + azlocillin (400 mg/kg/day). Ciprofloxacin significantly lowered vegetation titers of P. aeruginosa at days 6 and 10 of therapy compared with netilmicin + azlocillin (P less than 0.001). Similarly, ciprofloxacin was significantly more effective in sterilizing vegetations (P less than 0.005), curing P. aeruginosa endocarditis (P less than 0.001), and preventing bacteriological relapse after discontinuing antibiotic therapy (P less than 0.005). Both antibiotic regimens were equally effective in sterilizing renal abscesses. Resistance to azlocillin was occasionally observed in vivo among P. aeruginosa isolates within cardiac vegetations during the second week of therapy, but not to ciprofloxacin or netilmicin.

Constant rate of infusion--improvement of tests for teratogenicity and embryotoxicity.

Sodium salicylate was used as a model substance to investigate whether the embryotoxic effects on rat fetuses varies between two modes of administration. A marked increase in fetal adverse effects was observed at analgetic doses with the once-a-day bolus regimen compared to the constant rate input. The difference was less marked at antirheumatic levels.