Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group.

OBJECTIVE: To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections. DESIGN: Prospective, nonblind, randomized trial. SETTING: Multicenter trial conducted at 22 centers. PATIENTS: Two hundred eleven patients were enrolled and 121 were evaluable for the analysis of both clinical and bacteriologic efficacy. INTERVENTIONS: One hundred four patients were randomized to receive intravenous meropenem (1000 mg) every 8 hrs and 107 patients were randomized to receive intravenous ceftazidime (2000 mg) plus tobramycin (1 mg/kg) every 8 hrs. Sixty-three meropenem-treated patients and 58 ceftazidime-tobramycin-treated patients were eligible for the analysis of clinical and bacteriologic efficacy. In the ceftazidime-tobramycin group, 32 (55%) evaluable patients received more than six doses of tobramycin, 24 (41%) received six doses or fewer, and two (3%) did not receive any tobramycin. MEASUREMENTS AND MAIN RESULTS: The analysis of efficacy was based on the clinical and bacteriologic responses at the end of treatment. Satisfactory clinical responses occurred in 56 (89%) of 63 of the meropenem-treated patients and in 42 (72%) of 58 of the ceftazidime-tobramycin-treated patients (p = .04). Corresponding bacteriologic response rates were 89% and 67%, respectively (p = .006). The frequency and profile of drug-related adverse events was similar across treatment groups. Seizures were reported in three meropenem-treated patients, but these seizures were considered by the investigator to be unrelated to treatment. CONCLUSIONS: Meropenem is well tolerated and more efficacious than the combination of ceftazidime and tobramycin for the initial empiric treatment of hospital-acquired bacterial pneumonia.

Treatment of urinary tract infections: selecting an appropriate broad-spectrum antibiotic for nosocomial infections.

Clinical and in vitro data indicate that cefepime, a fourth-generation cephalosporin, may be a valuable addition in the treatment of serious infections. In this study, hospitalized patients with complicated and uncomplicated urinary tract infection (UTI), for which parenteral therapy was appropriate, were enrolled in a 2:1 ratio open, randomized trial comparing the efficacy and safety of cefepime and ceftazidime. A total of 180 patients, including 6 with concurrent bacteremia, were evaluated for their response to cefepime (n = 118) or ceftazidime (n = 62), both of which were administered by intravenous infusion or intramuscular injection in doses of 500 mg every 12 hours. In cases of complicated UTI, cefepime produced a satisfactory clinical response in 83 of 93 (89%) patients and eradicated 83 of 98 (85%) pathogens. A satisfactory clinical response to ceftazidime was experienced by 43 of 50 (86%) patients; and in 39 of 50 (78%) cases pathogens were eradicated. In uncomplicated cases, the clinical response and bacterial eradication rates for cefepime were 23 of 25 (92%) and 22 of 26 (85%), respectively, and for ceftazidime 12 of 12 (100%) and 11 of 12 (92%). Of the 6 patients with concomitant bacteremia, 5 received cefepime and 1, ceftazidime. The infecting organisms, Escherichia coli and Proteus mirabilis, were eradicated in all cases, although one cefepime-treated patient had an unsatisfactory clinical response. The most common adverse events in both groups were headache, diarrhea, and vomiting; most events were unrelated to therapy. Adverse events forced only a 2% withdrawal of patients in either group. There was local tolerance to both agents, and abnormalities in laboratory values were judged to be clinically insignificant. The results of this study indicate that cefepime can be used safely and successfully to treat both complicated and uncomplicated nosocomial infection of the urinary tract, including cases associated with concurrent bacteremia. Moreover, its safety profile appears comparable to those of other cephalosporins, and local tolerance is similar to that of ceftazidime. No patient in either group required discontinuation of therapy because of local intolerance at the infusion or injection site.

A multicenter comparative study of meropenem and imipenem/cilastatin in the treatment of complicated urinary tract infections in hospitalized patients.

The safety and efficacy of meropenem and imipenem/cilastatin were compared in the treatment of hospitalized patients with complicated urinary tract infections (UTIs) in a prospective, multicenter, open, parallel-group trial. Patients were randomized to receive 500-mg intravenous doses of either meropenem every 8 hours (n = 116) or imipenem/cilastatin every 6 hours (n = 119). Data from 95 patients given meropenem and 82 patients given imipenem/cilastatin were included in the evaluation of efficacy. Meropenem produced satisfactory clinical and bacteriologic responses in 99% and 90% of cases, respectively. These results were similar to those obtained with imipenem/cilastatin, which produced clinical improvement in 99% of cases and bacteriologic improvement in 81%. Two patients given meropenem and five patients given imipenem/cilastatin developed superinfections. The rate of relapse was similar in the two groups. Patients who received meropenem had fewer drug-related adverse reactions than did recipients of imipenem/cilastatin (8% vs. 19%). The results of this study demonstrate that meropenem is a safe and effective alternative to imipenem/cilastatin in the treatment of hospitalized patients with complicated UTIs.

Meropenem versus imipenem/cilastatin in the treatment of hospitalized patients with skin and soft tissue infections.

Meropenem is a new carbapenem antibiotic shown to resist degradation by renal dehydropeptidase I. In a multicenter, open-label, prospective trial, we compared the efficacy and safety of meropenem with imipenem/cilastatin in patients with skin and soft tissue infections. Patients received either 500 mg of meropenem every 8 hours (n = 184) or 500 mg of imipenem/cilastatin every 6 hours (n = 193), by intravenous infusion for an average of 6 to 7 days. Satisfactory clinical responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic response rates were high as well: 94% with meropenem and 91% with imipenem/cilastatin. Between-group differences in satisfactory response rates were not significant (95% confidence interval, -2.29 to 6.93 [clinical]; -2.73 to 10.39 [bacteriologic]). Overall pathogen eradication rates (for aerobes and anaerobes) were slightly higher for meropenem. Elevated liver enzymes were the most frequent adverse events in each treatment group. Meropenem was well tolerated and as effective as imipenem/cilastatin in treatment of hospitalized patients with skin and soft tissue infections.

A comparison of ampicillin/sulbactam and cefuroxime in the treatment of patients with bacterial infections of the lower respiratory tract.

Ampicillin/sulbactam (1 to 2 g ampicillin and 0.5 to 1 g sulbactam, administered intravenously once every 6 hours) and cefuroxime (750 mg to 1.5 g, administered intravenously once every 8 hours) were compared to determine their efficacy and safety in treating patients with lower respiratory tract infections of bacterial etiology. Nineteen of the 41 patients treated with ampicillin/sulbactam and 18 of the 44 patients treated with cefuroxime were assessable for efficacy. The clinical responses to the 2 treatments were comparable: 5 (26%) patients treated with ampicillin/sulbactam were cured and 14 (74%) were improved. Five (28%) patients who received cefuroxime were cured, 12 (67%) were improved, and treatment failed in 1 patient (6%) (P = 0.569). Similarly, no significant difference was noted between the bacteriologic responses to the two antimicrobials (P = 0.486). All isolates from the patients treated with ampicillin/sulbactam were eradicated, as were all isolates in 17 (94%) of the patients treated with cefuroxime. A superinfection occurred in 1 (6%) patient who received cefuroxime. Adverse reactions were rare and occurred in 3 patients from each treatment group.

A multicenter comparative study of cefotetan once daily and cefoxitin thrice daily for the treatment of infections of the skin and superficial soft tissue.

To compare the effectiveness of cefotetan administered at 2 g once a day with cefoxitin at 1 or 2 g three times a day in the treatment of hospitalized patients with skin and superficial soft tissue infections, 194 patients from eight centers were enrolled in an open, randomized trial. Most of the 104 evaluable patients in the cefotetan group and 50 in the cefoxitin group were young men with community-acquired, moderate or severe cellulitis, or abscesses of the upper and lower extremities caused by Staphylococcus aureus, Streptococcus species, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and other species of bacteroides, peptococcus species, and peptostreptococcus species. The mean duration of treatment was 7.5 days for cefotetan and 7.1 days for cefoxitin. A successful clinical response was achieved in 97 percent of the cefotetan patients and in 94 percent of the cefoxitin patients. Of the 88 and 39 bacteriologically evaluable patients in the cefotetan and cefoxitin groups, respectively, a satisfactory bacteriologic response occurred in 96 percent and 87 percent of the patients. No clinically significant changes in clinical laboratory determinations were noted. The incidence of adverse reactions in the cefotetan group (17 percent) was significantly different from that for the cefoxitin group (6 percent) (p less than 0.05); however, the incidence of treatment-related reactions was not significant and the events were mild. Discontinuation of therapy was necessary only in two patients in whom allergic-type reactions developed. A once-daily regimen of cefotetan was as effective as thrice-daily cefoxitin in this study in the treatment of primarily polymicrobial, moderate, or severe infections of the skin and superficial soft tissue.

Clinical value of paired sputum and transtracheal aspirates in the initial management of pneumonia.

One hundred young adults with acute pneumonia were prospectively studied to determine the impact of the transtracheal aspiration (TTA) Gram stain on immediate management. Sputum and TTA interpretations by staff and housestaff were compared. After a management plan was elected based on sputum Gram stain interpretation, the TTA was evaluated and the final plan chosen. A change in treatment after the TTA was available occurred in eight cases, and this was an appropriate change in only five. The putative pathogen as identified by TTA culture was correctly predicted after sputum Gram stain interpretation in 36 to 62 percent of cases and after TTA interpretation in 37 to 62 percent. This indicates significant observer variation but not superiority of one type of specimen over the other. In most cases, paired sputum and TTA Gram stain were both read correctly or incorrectly. When differences occurred, sputum interpretations were as likely to be correct as were TTA interpretations. The TTA Gram stain offered no advantage over sputum Gram stain in the initial management of acute pneumonia in this young adult military population.

Comparison of cefonicid and cefamandole for the treatment of community-acquired infections of the lower respiratory tract.

Cefonicid is a new "second-generation" parenteral cephalosporin with an antibacterial spectrum similar to that of cefamandole. It has, however, somewhat less activity in vitro against gram-positive cocci. Because of high blood levels and long serum half-life, daily dosing with cefonicid is feasible. Patients with community-acquired infections of the lower respiratory tract were randomized in a ratio of 2:1 to receive cefonicid once daily or cefamandole every 6 hr. All doses were 1,000 mg except for 13 patients given 500 mg of cefonicid. Of 100 patients evaluated, 66 received the study drug. Most infections were due to Streptococcus pneumoniae or Haemophilus influenzae. One-fourth of the patients had no demonstrable pathogen. Ninety-four percent of both groups were cured or improved by therapy. No significant toxicity or adverse effects were seen with cefonicid. One dose per day of cefonicid is adequate therapy for many patients having community-acquired pneumonia who might otherwise be treated with cefamandole.

Fungal infection of prosthetic joints: a report of two cases.

Two cases of yeast infection of prosthetic joints, caused by Torulopsis glabrata and Candida albicans are described. One case occurred 27 months after joint insertion. Neither patient had an underlying illness predisposing them to infection. Removal of the prosthetic device appears necessary for cure of such infection.

Yersinia enterocolitica septicemia.

We present a patient with Yersinia enterocolitica septicemia who relapsed after a course of apparently appropriate antibiotic therapy. A literature review of successfully managed patients with this infection suggests clinical efficacy of aminoglycosides if therapy is continued for at least two weekon are presented. Close follow-up after therapy is required for early recognition and prompt treatment of relapse.

Schistosomiasis in Saudi Arabian recruits. A morbidity study based on quantitative egg excretion.

We surveyed stool and urine specimens from 245 Saudi Arabian trainees for parasites. Schistosoma mansoni eggs were found in the stool in 66 (26.9%) and S. haematobium eggs were recovered from the urine in 1 (0.4%). Additional parasites were recovered in 167 (68.2%) of the survey group and were not more common in those with schistosomiasis (P greater than .10). Schistosome egg counts ranged from 0--6,320 eggs/g feces (mean 447.9). When patients with high egg counts (over 400 eggs/g) were compared with uninfected controls, abdominal complaints and fatigue were found to be more frequent (P less than .05) in the infected group, as was eosinophilia (P less than .001). Other laboratory and physical examination findings were equally present in both groups. This study reaffirms the value of quantitative examination of stool specimens for schistosome eggs.

Anaerobic bacteriuria in a male urologic outpatient population.

We screened 517 urine samples from male outpatients, many of whom had underlying urinary tract pathology, for anaerobic and aerobic bacteriuria. Of the 153 specimens containing greater than 10(5) bacteria per ml. 20% yielded anaerobes only and an additional 6% revealed mixed anaerobic and aerobic growth. Pyuria was found more frequently in samples containing anaerobic bacteriuria than in those containing no growth but not as frequently as when aerobic bacteria were present. The high counts of anaerobic bacteria in first-voided specimens compared to midstream and post-prostatic massage aliquots suggested a urethral source for most bacteria. However, suprapubic aspiration of bladder urine demonstrated the organism in 2 of 10 patients with high numbers of anaerobes and pyuria in voided samples.

Microscopic and bacteriological comparison of paired sputa and transtracheal aspirates.

Ninety-six sputum specimens from patiens with pneumonia were microscopically screened for leukocytes and buccal squamous epithelial (BSE) cells. Cultures of these specimens were compared with cultures of paired transtracheal aspirates (TTA). Agreement between sputa with less than 25 BSE cells per 100X field and TTA was good (79%). Only 27% of the specimens with greater than 25 BSE cells per 100X field agreed with TTA. Sixty-six of the sputa were of group 5 quality, i.e., greater than 25 leukocytes and less than 10 BSE cells per 100X field. A potential pathogen growing in one of these specimens was 94% predictive of growth in the TTA. If a group 5 sputum was negative for a potential pathogen, there was a 45% chance that a fastidious organism had been overgrown or overlooked. The presence of definite lower tract secretions in group 5 sputa as determined by visualizing bronchial epithelial cells and alveolar macrophages did not significantly increase the diagnostic value of these specimens. Microscopic screening of sputum before culture with rejection of selected specimens can increase the value of sputum in determining the etiology of bacterial pneumonia.

Salmonella abscess. A potential nosocomial hazard.

Abscess formation by Salmonella species is an uncommon but significant manifestation of salmonellosis. These localized infections can serve as sources for hospital outbreaks. Appropriate isolation measures and management require early recognition. Three patients with Salmonella abscess were admitted to hospital with a diagnosis other than Salmonella infection. In two, admitted with diagnoses of cholelithiasis and acute appendicitis, respectively, postoperative Salmonella infections developed. A third was diagnosed as having traumatic epididymitis, but was found to have Salmonella orchitis. Appropriate antibiotic therapy was effective in two of the three instances; the other resolved spontaneously. There were no recognized nosocomial infections related to these patients, in spite of delayed diagnosis and treatment. Proper routine wound care plus handwashing after patient contact can minimize the spread of these organisms from unsuspected infections.