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Cefaclor, a new oral cephalosporin, was compared in vitro with cephalexin and cephradine against 233 organisms. Evaluations were performed in Mueller-Hinton and nutrient broth and agar using two inoculum sizes. In agar, cefaclor had greater antibacterial activity than either cephalexin or cephradine against isolates of Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Klebsiella pneumoniae, and Salmonella typhi. All three drugs were relatively inactive against isolates of enterococci, Enterobacter species, and indole-positive Proteus. Cefaclor, however, did exhibit the greatest activity of the three antibiotics against these organisms. Although there was wide variability with respect to test parameters, the broth results generally paralleled the agar results. In nutrient broth a clear separation of the results with these three cephalosporins was seen with K. pneumoniae, E. coli, and S. typhi. Cefaclor was the most active, cephalexin had intermediate activity, and cephradine was the least active. From the data obtained in this in vitro study, it can be concluded that cefaclor, which has a substituted chloro group attached to the molecule, had increased antibacterial activity over cephalexin and cephradine. Comparative clinical trials with cefaclor will determine whether the differences outlined above are of clinical significance.

Eighty-two hospitalized adult patients were randomized to treatment with gentamicin or tobramycin. Serum levels were compared to computer-derived mathematically predicted levels to evaluate predictability of gentamicin and tobramycin serum levels. When comparable dosages were used mean peak gentamicin levels (4.87 micrograms/ml) did not differ from those after tobramycin (4.31 micrograms/ml). Seventy-three percent of patients had peak levels after gentamicin greater than 4.0 micrograms/ml compared to 46% after tobramycin. Factors purported to influence predictability of aminoglycoside serum levels were examined. In 46 of 74 patients whose actual body weight was 10 to 35 kg less than estimated ideal body weight levels after both drugs were lower than predicted. Serum levels were also lower than predicted in 7 of 11 patients with ascites, 6 of 7 patients receiving carbenicillin therapy, and 17 of 29 patients who had pneumonia. Neither hematocrit nor temperature appeared to influence predictability of serum levels. A comparison of methods used to obtain computer-derived predicted levels showed that ideal body weight provided the most accurate prediction. Differences between predicted and measured levels were established when calculations were based on actual body weight (P = 0.009) or on surface area (P = 0.003 for peak and 0.023 for trough levels).

Laminar air flow isolation and decontamination procedures were evaluated in a prospective randomized study in patients with aplastic anemia or acute leukemia undergoing marrow transplantation from HLA-matched siblings. Patients transplanted in the laminar air flow group had significantly less septicemia and major local infections than did patients in the control group. Nineteen of 46 laminar air flow patients and six of 44 control patients are alive at present. In patients with aplastic anemia the survival was 13 of 17 in the laminar air flow group compared with four of 17 in the control group. In patients with acute leukemia the survival was six of 29 in the laminar air flow group versus two of 27 in the control group. These differences were not statistically significant. Death in both the laminar air flow and control groups was predominantly due to interstitial pneumonitis or recurrent leukemia, which were unaffected by isolation and decontamination.

Antimicrobial prophylaxis prevents recurrent urinary tract infections in susceptible women, but its cost effectiveness has not been studied. In a recent placebo-controlled trial of urinary prophylaxis, we also assessed cost effectiveness using a decision analysis model. In our hospital the direct cost of 1 patient year of urinary prophylaxis approximates the cost of treating one episode of cystitis. In women with a baseline infection rate of three per patient year, the annual cost of prophylaxis ($85.82) was less than treatment of acute episodes of infection ($392.30). Sensitivity analyses showed that in women with three infections per year, prophylaxis became cost effective when charges per episode exceeded $42.00. In women with frequent episodes of cystitis, prophylaxis will be cost effective in most practice settings.

One hundred seventy-five consecutive marrow transplant patients who were treated in a protective environment for at least two weeks were studied to determine the usefulness of bacteriologic surveillance cultures for the prediction of bacteremia due to Staphylococcus aureus or aerobic gram-negative bacilli. Bacteremia with these organisms occurred in 15 patients (9%), and all patients were colonized with the respective organism before bacteremia occurred. Bacterial colonization was associated with a 17- to 174-fold increase in the relative risk of bacteremia. Negative predictive values were high, but positive predictive values were low owing to the infrequent occurrence of bacteremia. Surveillance cultures also predicted antibiotic sensitivities for all but one organism causing bacteremia. Bacteriologic surveillance cultures in the protective environment are thus useful both for the identification of patients at higher risk of bacteremia with certain types of organisms and for the identification of those who may fail to respond to antibiotic therapy as a result of infection with resistant organisms.

An outbreak of staphylococcal bacteremia in healthy, full-term neonates occurred in the newborn nursery at a large county hospital not employing prophylactic hexachlorophene bathing. Seven infants had staphylococcal bacteremia and one had omphalitis. Two of the three isolates obtained for phage typing were type 86, and the other was 3c/71. Staphylococcal colonization rate in the nursery was 64% when the outbreak was recognized; 86% of these isolates were type 86. No predominant phage type was isolated from nursery personnel. The outbreak followed a six-month preliminary study that showed a rise in staphylococcal colonization rate from 2.2% with hexachlorophene bathing to 67% with a nonhexachlorophene-containing preparation. In a community survey of infants born during the two months prior to the epidemic, seven of eight babies with lesions were infected with Staphylococcus aureus type 86.

Cefazaflur was tested in vitro against 262 strains of bacteria. Inhibitory and bactericidal concentrations were determined with two inoculum sizes of bacterial cells in Mueller-Hinton broth and nutrient broth. Agar dilution studies also were performed. When tested in agar, 5.0 mug or less of cefazaflur per ml inhibited almost all strains of Staphylococcus aureus, Escherichia coli, Klebsiella, and Proteus mirabilis. The drug was less active against Enterobacter and indole-positive Proteus, and 7.5 mug of antibiotic per ml inhibited approximately two-thirds to one-fourth of the strains. A concentration of 50 mug of cefazaflur per ml was required for inhibition of the enterococci. There was negligible activity against Pseudomonas. The drug demonstrated less activity in broth than in agar, and a major inoculum effect was seen with some strains. For example, with a lower inoculum, 2.5 mug of cefazaflur per ml killed all strains of E. coli, whereas with the higher inoculum, 7.5 mug of cefazaflur per ml, inhibited 64% and killed only 8% of strains. The activity of the drug for some strains was greater in Mueller-Hinton broth; for others, it was greater in nutrient broth. There were considerable differences in the results of the broth and agar studies for some species when the same medium was employed. Because of differences in activity found with different media, inocula, and method of testing, an evaluation of the eventual usefulness of cefazaflur must await the results of in vivo studies.

A burn patient with a multiply antibiotic-resistant Staphylococcus aureus infection was transferred to Harborview Medical Center from a burn unit in another state. Despite standard wound precautions, transmission to 34 patients occurred during the subsequent 15 months. Twenty-seven of the patients were infected. Disease included pneumonia, empyema, bacteremia, endocarditis, osteomyelitis, and burn and wound infections. Seventeen of the 34 patients died. Phage typing and plasmid analysis showed the spread of multiply resistant S. aureus from the burn unit to the surgical intensive care unit where a study evaluating the use of chloramphenicol in cases of bowel sepsis was in progress. During this period the organism became resistant to chloramphenicol by acquiring either of two chloramphenicol R-plasmids. Using plasmid profiles and antibiograms, four epidemic strains were identified that assisted in identifying patient and personnel reservoirs. The outbreak was controlled only after rifampin was added to vancomycin treatment of infected patients, which correlated with eradication of the carrier state.

In a randomized crossover trial, 38 women with recurrent urinary tract infections were assigned to use either continuous prophylaxis with trimethoprim-sulfamethoxazole or intermittent self-administered therapy (single-dose trimethoprim-sulfamethoxazole taken for acute urinary symptoms). The infection rate for patients on prophylaxis was 0.2 episodes/patient-year compared with 2.2 infections/patient-year for patients on self-administered therapy (p less than 0.001). Thirty-five of thirty-eight symptomatic episodes diagnosed by patients as infection were confirmed microbiologically, and 30 of the 35 infections responded clinically and microbiologically to patient-administered therapy with single-dose trimethoprim-sulfamethoxazole. No complications were seen in the 5 patients in whom therapy failed. The annual costs of prophylaxis and self-therapy were similar ($256 and $239, respectively) and both were less expensive than conventional therapy in women having 2 or more infections per year. In selected women, self-therapy is efficacious and economical compared with conventional therapy or prophylaxis.

Low-dose trimethoprim (TMP), trimethoprim-sulfamethoxazole (TMP-SMZ), and nitrofurantoin macrocrystals were found to be safe and effective as prophylaxis against recurrent urinary tract infections. Women given placebo had 2.8 infections per patient-year during the six-month study period, while women given TMP, TMP-SMZ, or nitrofurantoin had significantly lower infection rates (0.015 per patient-year). The effect of prophylaxis appeared to be limited to the period when the agents were taken. Only one patient had a TMP-resistant coliform isolated from cultures obtained during prophylaxis and six months afterwards. The sole factor associated with the recurrence of infection after prophylaxis was a history of three or more infections in the year preceding prophylaxis. Thirty-one of the 60 women in the trial were monitored for a mean of 6.1 years before and 3.2 years after they entered the study. Analysis of infection rates indicated that about half these women were experiencing an infection cluster when they entered the study and that the prestudy baseline infection rate correlated with the poststudy rate. Thus, prophylaxis did not appear to exert a long-term effect on the baseline infection rate. Urinary prophylaxis generally appears to become cost-effective when the baseline infection rate exceeds two per patient-year.

Three bone marrow transplant recipients experienced right-sided intracardiac infection due to coagulase-negative Staphylococcus infection associated with Hickman catheter use. In each case, multiple blood cultures yielded coagulase-negative Staphylococcus organisms, and echocardiography demonstrated mass lesions or vegetations in the right atrium. Two patients appeared to have infected intracardiac thrombi without definite valvular involvement, whereas one had both an atrial mass and a tricuspid valve vegetation. All patients were treated with catheter removal and 4 weeks of antibiotic therapy, and one patient required cardiac surgery after failure of antibiotic therapy and an apparent paradoxic embolus to the central nervous system. Intracardiac infection is a rare but potentially fatal complication of Hickman catheter use. Echocardiography may be useful in establishing the diagnosis in suspected cases.

Cefoxitin has become one of the most used parenteral antibiotics in the United States, perhaps because of a broad spectrum of activity, including activity against Bacteroides fragilis, which makes the drug suitable for prevention and treatment of intraabdominal and pelvic infections. This review focuses on the use of cefoxitin in obstetric and gynecologic infections, with comparisons to older and newer antibiotics. Numerous studies have shown that cefoxitin is clearly effective; in most of these studies, however, either the initial infection rates were low or the sample sizes were small--circumstances making it difficult to establish the superiority of any one agent. Thus, the necessity of using a drug with activity against B. fragilis for prevention and treatment of pelvic infections has not been proven. Several antibiotics without such activity have been equally effective. Cefoxitin may be of particular value when combined with surgical drainage of pelvic abscesses, infections in which control of B. fragilis may be especially important to outcome.

Ampicillin and tetracycline, in doses of 2 g a day, were compared in the treatment of acute exacerbations of chronic bronchitis. Seventy-nine patients were followed for 3 to 29 months and were treated for 118 exacerbations. Clinical improvement occurred after 10 days of treatment with either drug in over 80% of the cases. Haemophilus influenzae and Diplococcus pneumoniae were eradicated from the sputum more than 60% of the time, but in general there was a poor correlation between bacteriological clearing and clinical response. The effect of chemoprophylaxis with ampicillin and tetracycline in doses of 1 g a day on the frequency of acute exacerbations of bronchitis was compared with that of a placebo. Seven hundred eighty prophylactic regimens, consisting of one capsule every 12 hr for 5 days beginning with the first sign of a cold, were prescribed for 76 patients. Irrespective of the regimen, an acute exacerbation of bronchitis was encountered at approximately 13% of the follow-up visits to the clinic.