A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin.

OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.

Survey of susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates to 26 antimicrobial agents: a prospective U.S. study.

An antimicrobial susceptibility surveillance study of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates was performed during the winter of 1996-1997 in order to determine their susceptibilities to 5 fluoroquinolones and 21 other antimicrobial agents. Broth microdilution MICs were determined for 2, 752 isolates from 51 U.S. medical centers. Of the 1,276 S. pneumoniae isolates, 64% were susceptible, 17% were intermediate, and 19% were highly resistant to penicillin. On the basis of the MICs at which 90% of isolates are inhibited and modal MICs, the hierarchy of the five fluoroquinolones from most to least active was grepafloxacin > sparfloxacin > levofloxacin = ciprofloxacin > ofloxacin. For S. pneumoniae isolates for which penicillin MICs were elevated, the MICs of the cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole were also elevated, but the MICs of the fluoroquinolones, vancomycin, and rifampin were not. The prevalence of penicillin-susceptible pneumococci varied by U.S. Bureau of the Census region (range, 44% in the East South Central region to 75% in the Pacific region). In addition, S. pneumoniae isolates from blood were significantly more susceptible to penicillin than those from respiratory, ear, or eye specimens, and pneumococci from patients

Comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial sinusitis.

This double-masked, multicenter, randomized clinical trial compared the efficacy and tolerability of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial maxillary sinusitis. A total of 263 patients with acute bacterial maxillary sinusitis were randomly assigned to receive 10 days of treatment with either cefuroxime axetil 250 mg twice daily (n = 132) or amoxicillin/clavulanate 500/125 mg 3 times daily (n = 131). Patients' responses to treatment were assessed once during treatment (6 to 8 days after the start of treatment), at the end of treatment (1 to 3 days posttreatment), and at follow-up (26 to 30 days after cessation of treatment). Clinical success, defined as cure or improvement, was equivalent in the cefuroxime axetil and amoxicillin/ clavulanate groups at the end-of-treatment and follow-up assessments. Patients in both groups showed improvements in symptoms of acute sinusitis at the during-treatment visit. Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events than treatment with cefuroxime axetil (29% vs 17%), primarily reflecting a higher incidence of gastrointestinal adverse events (23% vs 11%), particularly diarrhea. Two patients in the cefuroxime axetil group and 8 patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events (P = 0.06). These results indicate that cefuroxime axetil 250 mg twice daily is as effective as amoxicillin/clavulanate 500 mg 3 times daily in the treatment of acute sinusitis and produces fewer gastrointestinal adverse events. cefuroxime axetil, amoxicillin/clavulanate, acute sinusitis.

Clonal relationships among high-level penicillin-resistant Streptococcus pneumoniae in the United States.

During the past 6 to 7 years, the problem of antimicrobial resistance in Streptococcus pneumoniae has grown dramatically in the United States. Currently, approximately 26.5% of pneumococcal isolates express intermediate levels of resistance to penicillin; approximately 17.5% are highly penicillin resistant. We studied whether clonal relationships exist among current isolates of high-level penicillin-resistant S. pneumoniae (PRSP) in the United States. One hundred forty-seven PRSP isolates recovered in a 30-center surveillance study in the United States during 1994-1995 were characterized with respect to serotype, antimicrobial susceptibility pattern, and pulsed-field gel electrophoresis (PFGE) profile. Only six serotypes were observed among the 147 PRSP isolates examined in this study: 6A, 6B, 9A, 14, 19F, and 23F. One hundred three (70.1%) of the 147 strains were characterized by one of only nine PFGE types; 76 (51.7%) of the 147 isolates were characterized by only four PFGE profiles. Currently in the United States, most PRSP strains are represented by relatively few clonal groups.

In vitro activity of grepafloxacin and 25 other antimicrobial agents against Streptococcus pneumoniae: correlation with penicillin resistance.

Strains of Streptococcus pneumoniae from the United States that were susceptible, intermediately resistant, or highly resistant to penicillin were tested for susceptibility to 26 antimicrobial agents that have been used or considered for the treatment of patients with pneumococcal infections. The drugs tested included penicillins, one penicillin/beta-lactamase inhibitor combination, cephalosporins, macrolides, a lincosamide, fluoroquinolones, and four miscellaneous drugs (vancomycin, rifampin, tetracycline, and trimethoprim-sulfamethoxazole). The activities of the penicillins and macrolide agents were similar, but the activities within the cephalosporin and fluoroquinolone classes were often dissimilar. For the fluoroquinolones, the order of in vitro activity, from most to least active, was grepafloxacin, sparfloxacin, levofloxacin, ciprofloxacin, and ofloxacin. Increased resistance to penicillin in the pneumococcal isolates studied correlated with increased resistance to other penicillins, cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole but did not correlate with increased resistance to the fluoroquinolones, rifampin, or vancomycin. These findings may be helpful to health professionals selecting empiric therapy for respiratory tract infections involving S. pneumoniae.

Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study.

A total of 1,537 clinical isolates of Haemophilus influenzae were recovered in 30 U.S. medical center laboratories between 1 November 1994 and 30 April 1995 and were characterized in a central laboratory with respect to serotype and beta-lactamase production and the in vitro activities of 15 oral antimicrobial agents. Overall, 36.4% of the isolates were found to produce beta-lactamase. The rank order of activity of six cephalosporins on the basis of MICs was cefixime > cefpodoxime > cefuroxime > loracarbef > or = cefaclor > cefprozil. On the basis of current National Committee for Clinical Laboratory Standards (NCCLS) breakpoints ages of isolates found to be resistant or intermediate to these agents were as follows: 0.1, 0.3, 6.4, 16.3, 18.3, and 29.8, respectively (National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. M7-A4, 1995). Azithromycin was, on a weight basis, the most potent of the macrolides tested in this study, followed by erythromycin and then clarithromycin. Azithromycin was typically fourfold more active than erythromycin, which was, in turn, slightly more active than clarithromycin. However, when compared on the basis of the frequency of resistance determined by using current NCCLS breakpoints, there was essentially no difference between azithromycin and clarithromycin, i.e., 0.5 and 1.9%, respectively (P = 0.086). Interpretive breakpoints for erythromycin MIC tests versus H. influenzae have not been developed. Resistance to other non- beta-lactam agents was variable, as follows: trimethoprim-sulfamethoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%; and rifampin, 0.3%. Two conspicuous findings in this study were the identification of 39 strains H. influenzae that were beta-lactamase negative but ampicillin intermediate or resistant (BLNAR) and, even more surprisingly, 17 beta-lactamase-positive isolates that were resistant to amoxicillin-clavulanate (BLPACR). Strains of H. influenzae in the first group have heretofore been very uncommon; organisms in the second group have not previously been described in the literature. The percentages of all study isolates comprised of BLNAR and BLPACR organisms were 2.5 and 1.1, respectively. Overall resistance to ampicillin was thus 38.9%, and that to amoxicillin-clavulanate was 4.5%.

Prevalence of antimicrobial resistance among 723 outpatient clinical isolates of Moraxella catarrhalis in the United States in 1994 and 1995: results of a 30-center national surveillance study.

Seven hundred twenty-three isolates of Moraxella catarrhalis obtained from outpatients with a variety of infections in 30 medical centers in the United States between 1 November 1994 and 30 April 1995 were characterized in a central laboratory. The overall rate of beta-lactamase production was 95.3%. When the National Committee for Clinical Laboratory Standards MIC interpretive breakpoints for Haemophilus influenzae were applied, percentages of strains found to be susceptible to selected oral antimicrobial agents were as follows: azithromycin, clarithromycin, and erythromycin, 100%; tetracycline and chloramphenicol, 100%; amoxicillin-clavulanate, 100%; cefixime, 99.3%; cefpodoxime, 99.0%; cefaclor, 99.4%; loracarbef, 99.0%; cefuroxime, 98.5%; cefprozil, 94.3%; and trimethoprim-sulfamethoxazole, 93.5%.

Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30-center national surveillance study.

A total of 1,527 clinically significant outpatient isolates of Streptococcus pneumoniae were prospectively collected in 30 different U.S. medical centers between November 1994 and April 1995. Overall, 23.6% of strains were not susceptible to penicillin, with 14.1% intermediate and 9.5% high-level resistant. The frequencies of recovery of intermediate and high-level resistant strains varied considerably between different medical centers and in different geographic areas. In general, intermediate and high-level penicillin resistance was most common with isolates of S. pneumoniae recovered from pediatric patients. The in vitro activities of 22 other antimicrobial agents were assessed against this collection of isolates. Ampicillin was consistently 1 twofold dilution less active than penicillin. Amoxicillin and amoxicillin-clavulanate were essentially equivalent to penicillin in activity. The rank order of activity for cephalosporins was cefotaxime = ceftriaxone > or = cefpodoxime > or = cefuroxime > cefprozil > or = cefixime > cefaclor = loracarbef > cefadroxil = cephalexin. The National Committee for Clinical Laboratory Standards [Performance Standards for Antimicrobial Susceptibility Testing, Sixth Information Supplement (M100-S6), 1995] has established MIC breakpoints for resistance (i.e., > or = 2 micrograms/ml) with three cephalosporins versus S. pneumoniae, namely, cefotaxime, ceftriaxone, and cefuroxime. The overall percentages of strains resistant to these three antimicrobial agents were 3, 5, and 12, respectively. The overall frequency of resistance was 10% with all three macrolides examined in this study, clarithromycin, erythromycin, and azithromycin. The overall percentages of chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole resistance were 4.3, 7.5, and 18, respectively. The resistance percentages among the cephalosporins, macrolides, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole were consistently higher among penicillin-intermediate strains than among susceptible isolates and even higher still among organisms expressing high-level penicillin resistance. Multiply resistant strains represented 9.1% of the organisms examined in this study. Finally, rifampin resistance was uncommon (i.e., 0.5%), and vancomycin resistance was not detected. The quinopristin-dalfopristin combination was consistently active at concentrations of 0.25 to 4 micrograms/ml, but rates of resistance could not be determined in the absence of established interpretive criteria for MIC results.

Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. The Mupirocin Collaborative Study Group.

Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86-0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus.

Successful treatment of cat-scratch disease with ciprofloxacin.

Cat-scratch disease is usually a benign, self-limited disease. Infection may be asymptomatic but is commonly associated with painful regional lymphadenitis. Occasionally, disease may result in systemic symptoms and dissemination. Five adult patients, aged 24 to 57 years, were diagnosed as having cat-scratch disease, based on a positive history of cat scratches followed by typical symptoms including painful regional lymphadenitis, malaise, and positive cat-scratch skin tests. Diagnostic evaluations revealed no other cause for the lymphadenitis. Three patients had not received prior treatment with antibiotics, and two patients had failed to improve on other antibiotics. All five were treated with oral ciprofloxacin, 500 mg by mouth, twice daily. All patients had dramatic improvement in symptoms within a few days and none has relapsed during follow-up. This is the first report of successful treatment of cat-scratch disease with ciprofloxacin, which appears to be an effective therapy for cat-scratch disease in adults.

Human immunodeficiency virus and the surgeon.

To assess the exposure risks for surgeons and nurses treating HIV infected patients at the Medical University Hospital and the Charleston Memorial Hospital, a retrospective review of HIV positive patients who underwent surgical procedures from 1985-1988 was undertaken. During that period, 150 patients tested positive for HIV of which 30 (20%) underwent 19 surgical procedures. The prevalence of HIV infected patients at our institution has been increasing over the last two years. 5.3% of the patients tested were positive for the virus. Evidence of drug abuse was not a predictive factor of HIV infection but homosexuality was present in 57% of our patients. The mean age of the surgical group was 34 years. Seventy-three percent of the patients underwent minor operations and 27% had major surgical procedures. Almost half of the operations were performed to treat an AIDS-related complication or as a diagnostic aid in the workup of the AIDS patient. Major operations performed were for treatment of a co-morbid condition not related to the HIV infection. Only two patients had operations for trauma. Operative mortality was 10% but no death was directly related to surgical intervention. In addition to universal precautions in the pre and postoperative period, operating room personnel must follow established protocols in the conduct of the operation to ensure the safety of all staff.

Cauda equina syndrome secondary to disseminated zygomycosis.

We describe a case of cauda equina syndrome secondary to disseminated zygomycosis. A 52-year-old man had myelodysplastic syndrome, progressive weakness of the lower extremities, and incontinence. Neuroradiological findings were consistent with lumbar stenosis and probable disk herniation. A lung lesion was also discovered on the chest roentgenogram. The patient's condition rapidly deteriorated after surgical decompression. Attempts at determining other etiologies were unsuccessful. At autopsy, disseminated zygomycosis was found affecting the lung and the vasculature of the cauda equina and lumbosacral nerve roots, with resultant focal demyelination of these structures. Ribbon-like hyphal elements were also present in the caudal roots. This opportunistic pathogen is discussed along with the diagnostic challenge presented by its unusual clinical presentation.

Refractory esophageal candidiasis associated with a low molecular weight plasma inhibitor of T-lymphocyte function.

In a patient with chronic esophageal candidiasis due to C. tropicalis that was refractory to mycostatin and ketoconazole, a generalized cell-mediated immunodeficiency state was detected. Samples of plasma from this patient inhibited T-lymphocyte function, suppressing both rosette formation and mitogen responsiveness of T-cells derived from the patient and from normal individuals. Following plasma exchange, the patient's immune defect resolved and her candida infection disappeared. On further analysis, the plasma inhibitory factor was found to be of low molecular weight (less than 10,000) and heat labile. Preliminary studies suggested that this inhibitor was candida-derived, since it was removed from plasma by anti-candida antibodies in solid phase. Immunodeficiency in chronic candidiasis may be improved by removal of circulating inhibitory factors through plasma exchange.

Phaeohyphomycosis complicating compound skull fracture.

Intracranial infection is a well-recognized complication of compound skull fractures. In most cases various bacteria are identified as the etiologic agents. Fungal infection complicating open head trauma is unusual. We describe a patient who contracted fatal meningoencephalitis due to Drechslera spicifera, a rarely pathogenic soil saprophyte, after open head trauma.

Immunoglobulin class of anti-Candida antibodies in patients with vaginal candidiasis.

Studies of the immunoglobulin class of circulating anti-Candida antibodies in patients with vaginal candidiasis were undertaken with the aim of answering the question of whether these antibodies are predominantly IgA or IgG. Earlier work resulted in conflicting data that we felt would be clarified by the use of a quantitative technique, FIAX fluoroimmunoassay, which could objectively measure the relative amounts of antibody of each class. Results using this assay and the indirect immunofluorescence assay on whole Candida cells demonstrate that the immunoglobulin class distribution of the circulating anti-Candida antibodies of these patients is similar to that seen in other forms of Candida infection, the predominant antibody class being IgG.