Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection.

OBJECTIVE: To compare trimethoprim-sulfamethoxazole (TMP-SMZ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections. DESIGN: Randomized, double-blind comparative trial. SETTING: A tertiary-care hospital. PATIENTS: One hundred and one intravenous drug users hospitalized with S. aureus infection. MEASUREMENTS: Cure and failure rates; blood and wound cultures; minimum inhibitory and bactericidal concentrations; serum inhibitory and bactericidal titers; temperature; leukocyte count; durations of treatment and hospitalization; and toxicity. RESULTS: Of 228 intravenous drug users, 101 had S. aureus infection and were included in the efficacy analysis (43 received TMP-SMZ and 58 received vancomycin). Methicillin-resistant S. aureus (MRSA) accounted for 47% of S. aureus isolates, and 65% of patients were bacteremic. Infections were cured in 57 of 58 vancomycin recipients and in 37 of 43 TMP-SMZ recipients (P less than 0.02). Failure occurred mostly in patients with tricuspid valve endocarditis and only in those with infection caused by methicillin-sensitive S. aureus (MSSA). The mean duration of bacteremia was 6.7 days in TMP-SMZ recipients and 4.3 days in vancomycin recipients. Among 222 subjects hospitalized for at least 24 hours, toxicity rates were similar for TMP-SMZ (23%) and vancomycin (20%) recipients; nausea and vomiting were associated with TMP-SMZ and inflammation at the intravenous site was associated with vancomycin. Forty-four percent of TMP-SMZ recipients and 29% of vancomycin recipients experienced side effects in the efficacy cohort (P greater than 0.05). CONCLUSIONS: Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections. However, all treatment failures occurred in patients with MSSA infection at any site. Therefore, TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection.

Single-dose cephalexin therapy for acute bacterial urinary tract infections and acute urethral syndrome with bladder bacteriuria.

The efficacy of single-dose therapy with 3 g of cephalexin was evaluated in 129 women with symptoms of acute uncomplicated lower urinary tract infections. Of 91 patients with significant bacteriuria, 61 (67%) were cured of their original infection; this was similar to the 54 to 79% cure rates reported in unselected populations of women of a wide age range treated for acute uncomplicated urinary tract infections with a single dose of amoxicillin or trimethoprim-sulfamethoxazole (J. Rosenstock, L. P. Smith, M. Gurney, K. Lee, W. G. Weinberg, J. N. Longfield, W. B. Tauber, and W. W. Karney, Antimicrob. Agents Chemother. 27:652-654, 1985; N. E. Tolkoff-Rubin, M. E. Wilson, P. Zuromskis, I. Jacoby, A. R. Martin, and R. H. Rubin, Antimicrob. Agents Chemother. 25:626-629, 1984). The cure rates of (87%) for our younger patients, those less than 25 years of age, was better than that (46%) for our patients over 40 years of age (P less than 0.001). Patients with infections that were negative in an antibody-coated bacteria test were cured at a significantly higher rate than those with infections that were positive in an antibody-coated bacteria test (71 versus 19%; P = 0.003). Those patients with infections caused by cephalexin-susceptible organisms were cured at a rate similar to that for patients with infections caused by cephalexin-resistant organisms (68 versus 50%; P = 0.62). The cure rate for suburban patients was 90%, versus 45% for inner-city patients (P = 0.008). Of the 28 women with acute urethral syndrome due to low-level bacteriuria, 27 were cured.

Pneumococcal psoas abscess.

Primary extrapulmonary pneumococcal disease has become a rarity in modern times. We describe a 40-year-old patient who developed an abscess of the psoas muscle as the only evidence of pneumococcal disease. A predisposing local condition was prior trauma of the psoas muscle, documented by the existence of myositis ossificans circumscripta. This case emphasizes the importance of considering unusual sites of involvement of pneumococcal disease.

Cephapirin therapy in infective endocarditis.

Ten patients, eight of them heroin addicts, with infective endocarditis were treated with cephapirin. Causative organisms included Staphylococcus aureus in six patients and viridans streptococci, S bovis, and S pneumoniae in one patient each. In one of the patients with endocarditis, both S aureus and an organism of the beta-Streptococcus group were simultaneously isolated. All patients except two, both with monomicrobial S aureus endocarditis, were cured. All isolates were inhibited by less than or equal to 0.5 micrograms/ml of cephapirin. Peak serum bactericidal activity greater than or equal to 32 times the minimal inhibitory concentration (MIC) of the causative organism was achieved in all cases after giving 2 gm IV every four hours. After using large inoculums of staphylococci for in vitro tests, we found that twofold to eightfold increases in MIC occurred. Cephapirin was well tolerated intravenously and high levels in serum were achieved without toxicity or accumulation of the drug.

In vitro susceptibility patterns of methicillin-resistant and-susceptible Staphylococcus auerues strains in a population of parenteral drug abusers from 1972 to 1981.

Since 1980, infections caused by methicillin-resistant (MR) Staphylococcus aureus have been epidemic among Detroit-area parenteral drug abusers. Because of the increasing importance of this pathogen, in vitro susceptibilities were compared for 39 isolates of MR S. aureus from 1980 to 1981, and for 56 strains of methicillin-susceptible (MS) S. aureus from 1972 to 1981, recovered from drug abusers with community-acquired infections. Agar dilution studies were performed at 35 degrees C, and minimal inhibitory concentrations were determined after incubation for 18 and 48 h. MR S. aureus exhibited cross-resistance to other beta-lactam antibiotics which frequently required 48 h for expression. MR S. aureus isolates were also resistant to tetracycline, clindamycin, tobramycin, and amikacin. All MR S. aureus isolates investigated synthesized an aminoglycoside 4'-nucleotidyltransferase. Emergence of resistance to cefotaxime, tetracycline, and clindamycin was noted among current MS S. aureus isolates. Vancomycin, fusidic acid, trimethoprim/sulfamethoxazole, and rifampin were the most active agents against MR S. aureus and were equally effective against MS S. aureus.

Osteomyelitis of the pubis. Report of seven cases.

Seven cases of osteomyelitis of the pubis are reported. Predisposing factors leading to osteomyelitis included parenteral drug abuse in six patients and pelvic surgery in one patient. The average duration of symptoms before diagnosis was three weeks. Needle aspiration of the symphysis pubis was performed in five patients, and culture results were positive in three of them. Two patients with negative cultures of needle aspirates had positive cultures from open biopsy specimens of the symphysis pubis. Blood cultures were done in all patients, and results were positive in two of them. Pseudomonas aeruginosa was the responsible pathogen in five patients, Escherichia coli in one, and Staphylococcus aureus in one. Most patients required several weeks of antibiotic therapy. None required surgical debridement.

The effect of inoculum, culture medium and antimicrobial combinations on the in-vitro susceptibilities of Legionella pneumophila.

The in-vitro susceptibility of 14 strains of Legionella pneumophila to 17 anti-microbial agents were determined. The most active antibiotics were cefoxitin, erythromycin and doxycycline while the least active were cephalothin, cefamandole and cefazolin. Subculturing, type of medium and duration of incubation did not alter the effect of the antimicrobial agents. A change in the inoculum size, from 10(4) to 10(6) cfu, increased MICs two- to sixfold. Erythromycin was not synergistic with gentamicin, tobramycin or amikacin.

Effect of clavulanic acid on minimal inhibitory concentrations of 16 antimicrobial agents tested against Legionella pneumophila.

A total of 15 Legionella pneumophilia isolated were tested against 16 antimicrobial agents used singly and in combination with clavulanic acid. When combined with clavulanic acid, 4 of the 16 antimicrobial agents produced no enhanced effect. However, the minimal inhibitory concentrations of 12 of the antimicrobial agents were reduced by one-half to one-third when in combination with clavulanic acid. These reductions reflected only a one-dilution decrease, however, in the original minimal inhibitory concentrations. Thus, clavulanic acid combinations appear to be only nominally effective beta-lactamase inhibitors against L. pneumophilia.

Antimicrobial susceptibility of Legionella pneumophila Serogroups I--IV.

Strains of Legionella pneumophila from 10 geographic areas were evaluated for their in vitro susceptibility to 14 antimicrobial agents. Included in this study were clinical and environmental isolates as well as strains from all 4 known serogroups. The minimal inhibitory concentration was established by agar dilution with a Steers replicator. The inhibitory index was then calculated considering the mean peak serum level for the associated antibiotic. Rifampicin, cefoxitin, chloramphenicol, ticarcillin, and parenteral erythromycin had the highest inhibitory indices. The only difference among serogroups was the increased susceptibility among serogroup II isolates to the penicillins and the increased susceptibility of serogroups III and IV to sulfamethoxazole-trimethoprim. Though there have been recent reports of the inadequacy of oral erythromycin in clinical cases of Legionnaires' disease, there was no erythromycin resistance noted among the 14 isolates tested.

The increasing importance of polymicrobial bacteremia.

Polymicrobial bacteremia increased from 6% in 1970 to 13% in 1975 in patients with bloodstream infections. This type of serious infection most commonly complicated genitourinary (27%) and gastrointestinal (26%) conditions, frequently followed invasive procedures (68%), was more common in hospitalized patients (73%), and was often associated with malignancies (25%) or immunosuppressive or cancer chemotherapy (34%). Although polymicrobial endocarditis was more commonly encountered in recent years, this infection accounted for only 4.5% of patients with multiple organism bacteremias. Gram-negative aerobic bacteria were isolated from 62% and anaerobic bacteria in 39% of patients with polymicrobial bacteremia compared with 37% and 14%, respectively, in patients with monomicrobial bacteremia. In the 88 patients with polymicrobial bacteremia, the mortality was 44.5%, compared with 18.0% in patients with monomicrobial bacteremia.

Ceforanide: in vitro and clinical evaluation.

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at

The compromised host and Legionnaires' disease.

Pneumonia caused by Legionnaires' disease bacterium was recognized in eight patients during a 7-month period. The patients were immunosuppressed by their underlying illness, corticosteroid therapy, and other exogenous immunosuppressive agents. Five of the patients had received immunosuppressive therapy for less than 16 days. Clinical presentation was similar to that of other bacterial pneumonias in compromised patients. Legionnaires' disease progressed to necrotizing pneumonia with abscess formation and respiratory failure in two patients. Diagnosis was made by [1] culture of lung tissue and bronchial washings; [2] direct fluorescent antibody staining of lung tissue, sputum, and bronchial washings; and [3] serologic evidence of infection. Therapy with oral erythromycin was ineffective. Intravenous erythromycin was given to six patients, with a good response. However, two patients showed further clinical improvement after rifampin was added. Because this illness may be more severe in compromised hosts, open lung biopsy and special microbiologic tests should be done when Legionnaires' disease is suspected.

Parenteral cephalothin therapy for pelvic gonococcal infections.

The efficacy of intravenous cephalothin was studied prospectively in 20 patients with acute pelvic inflammatory disease, all of whom presented with lower abdominal pain, cervical and adnexal tenderness, fever, and leukocytosis. Blood, cervical, and cul-de-sac cultures were obtained on admission. The latter was transported anaerobically and inoculated in routine and prereduced medium. Transgrow medium with trimethoprim was used for endocervical cultures. Neisseria gonorrhoeae was isolated from the endocervix in 15 patients and from the cul-de-sac in four patients. All received intravenous cephalothin, 2 gm every four hours for seven days. Clinical improvement was observed in 48 to 78 hours. The cervical cultures were negative for N. gonorrhoeae after 48 hours, at the completion of treatment, and two weeks post-treatment. The drug was well tolerated. It was concluded that cephalothin intravenously is an acceptable alternative antibiotic for the treatment of gonococcal pelvic infection.

Polymicrobial infective endocarditis: an increasing clinical entity.

Polymicrobial endocarditis was very uncommon until ten years ago. However, since that time, at least 21 cases were reported, and 10 patients with this mixed infection were seen at our hospital. All, except one of these infections, occurred in patients who had undergone heart surgery or abused intravenous drugs. Although, generally clinically indistinguishable from mono-microbial endocarditis, these mixed infections carried a very high mortality rate (greater than 30 per cent), and an unusually large number of the patients (greater than 50 per cent) needed heart surgery either to control the infection or to repair cardiac defects resulting from the infection. The prognosis depended on the species rather than the number of organisms isolated and on aggressive antimicrobial and surgical therapy.

Bacteremia, endocarditis, and the Hancock valve.

Among 373 patients with porcine xenografts, there were 27 instances of exposure of the xenograft to bloodstream or endocardial infection in 22 patients. Nine patients underwent 10 separate insertions of xenografts for active infective endocarditis. There were no early infections or valve failures. Three patients returned with a late prosthetic valve endocarditis (PVE) due to a new infection. There were 6 instances of bacteremia early after xenograft valve insertion with no early infection, no valve dysfunction, and 1 instance of late PVE. Eleven patients had PVE on a porcine xenograft. Blood cultures in the 10 patients treated with antibiotics promptly became negative. There were 3 valve-related deaths: 2 from valve incompetence and 1 from mitral and aortic xenograft stenosis. Our experience suggests that the Hancock porcine xenograft is: (1) as resistant to infection as are rigid prostheses in active infective endocarditis; (2) resistant to early postoperative bacteremias; and (3) easier to sterilize than rigid prostheses and more durable than other tissue valves in the face of PVE.

Tuberculous meningitis in an urban general hospital.

We analyzed the clinical and laboratory findings of 19 patients with tuberculous meningitis seen between 1966 and 1974 at the Henry Ford Hospital. Eighteen patients were adults at the time of diagnosis. In eight patients, the history suggested that the infection with the tubercle bacillus had occurred in the remote past. Cerebrospinal fluid analysis was often typical for tuberculous meningitis; stains for Mycobacterium tuberculosis were usually negative. Of 16 patients who were treated, five died and five suffered permanent neurological sequelae. The addition to rifampin to isoniazid therapy did not improve either survival or permanent sequelae. We were not able to analyze the effect of steroids on the disease.