Single-dose compared with 3-day norfloxacin treatment of uncomplicated urinary tract infection in women. Canadian Infectious Diseases Society Clinical Trials Study Group.

UNLABELLED: BACKGROUND--This study was undertaken to determine whether therapy for acute uncomplicated urinary tract infection in women with single-dose therapy with norfloxacin was superior to 3 days of norfloxacin therapy in efficacy or adverse effects. METHODS--The study was a multicenter, prospective, randomized, double-blind trial. Women with acute, uncomplicated urinary tract infection were randomized to receive norfloxacin, 800 mg as a single dose or 400 mg twice daily for 3 days. Clinical and laboratory evaluations were obtained before therapy and at days 3 and 7 and 4 to 6 weeks after initiation of therapy. RESULTS--The 83 subjects for whom data could be evaluated who received 3-day therapy had significantly improved outcome compared with the 73 subjects for whom data could be evaluated who received single-dose therapy at 3 days and 7 days after initiation of therapy. At 4 to 6 weeks, 88% of subjects who received 3 days of therapy remained cured, compared with 78% who received single-dose therapy. Three-day and single-dose therapy were equivalent for Escherichia coli infection, but single-dose therapy was significantly less effective for other organisms, primarily because of failure of treatment of Staphylococcus saprophyticus infection. Women older than 40 years were significantly less likely to be cured with either treatment regimen and with single-dose therapy. Adverse effects were similar for both treatment regimens. CONCLUSIONS: -Three days of norfloxacin therapy is more effective than single-dose therapy for women with acute, uncomplicated urinary tract infection. The two regimens are equally effective for E coli infection, but single-dose therapy is ineffective for S saprophyticus.

Group B streptococcal necrotizing fasciitis and streptococcal toxic shock-like syndrome in adults.

Necrotizing fasciitis, which is a severe and uncommon infection involving the subcutaneous tissues, is usually caused by group A streptococci. To our knowledge, however, group B streptococci (Streptococcus agalactiae) have been reported to cause necrotizing fasciitis in only 4 instances (2 involving neonates) over the past 4 decades. We report 3 cases of group B streptococcal necrotizing fasciitis in adults that occurred in southern Ontario and Quebec within a 10-month period. All 3 patients had significant underlying illness, and all required surgical debridement in addition to antibiotic therapy. One of the cases fulfilled the criteria for streptococcal toxic shock-like syndrome. Group B streptococcus has been recognized as a frequent cause of serious disease in adults. It has become evident over the past decade that invasive streptococcal infections are on the increase. We speculate that group B streptococcus has recently acquired an increased ability to cause necrotizing fasciitis and suggest that this may represent the emergence of a new clinical syndrome in adults.

Comparative efficacy of teicoplanin and cefazolin for cardiac operation prophylaxis in 3027 patients. The ESPRIT Group.

OBJECTIVE: Cephalosporins, especially cefazolin, are widely used in the prevention of postoperative wound infections after cardiac operations. As more and more Staphylococcus aureus and Staphylococcus epidermidis strains are becoming resistant to cephalosporins and other antibiotics, alternative agents, such as glycopeptides, are often used as prophylaxis. We performed a multicenter double-blind randomized controlled trial comparing teicoplanin, a glycopeptide antibiotic, with cefazolin. METHODS: A total of 3027 adult patients undergoing elective coronary artery bypass grafting, valve operations, or both were randomized to a single dose of teicoplanin (15 mg/kg) or a 2-day course of cefazolin (2 g initial dose, followed by 1 g every 8 hours for 6 more doses). Patients were followed up for a total of 6 months postoperatively. The primary objective was to compare, between groups, the incidence of surgical infections up to 30 days postoperatively. Secondary objectives were incidence of other infections, other complications, and death. RESULTS: A total of 3027 patients were randomized to receive either teicoplanin (n = 1518) or cefazolin (n = 1509). Thirty days postoperatively, there was a trend to more deep sternotomy wound infections in the teicoplanin group (31 vs 18, P =. 087), which became significant by 6 months (36 vs 19, P =.032). One hundred percent of the gram-positive strains infecting patients were susceptible to teicoplanin, whereas 8.3% were resistant to cefazolin. Pneumonia and urinary tract infections were more common in the teicoplanin group. Deep wound infections of the leg were more common in the cefazolin group. CONCLUSIONS: Cefazolin was more effective prophylaxis than teicoplanin against postoperative wound infections after elective cardiac operations. Infection rates were low with either treatment.

Transmission of hepatitis C in a pharmacologic study.

OBJECTIVE: To describe an outbreak of hepatitis C in a clinical research study. DESIGN: Observational study. SETTING: Tertiary-care hospital. PATIENTS: Healthcare workers who volunteered to be subjects in a study of the metabolic effects of inhaled and oral corticosteroids who were unwittingly exposed to hepatitis C virus (HCV). METHODS: Epidemiological investigation and serological analyses. RESULTS: One chronic carrier of HCV was identified. Four fellow workers volunteering in the studies became infected with HCV, with 96% homology among strains. There was no evidence of spread from infected healthcare workers to patients on whom they had performed arterial punctures (2 of 214 positive, unrelated to each other and to the outbreak strain). CONCLUSION: Infection control standards in clinical research must be maintained vigorously to prevent transmission of blood-borne pathogens such as HCV.

Aortitis with multiple aneurysms mimicking infective endocarditis.

Aortitis usually produces aortic insufficiency by aortic root dilation. In rare cases the inflammation may involve the aortic valve cusps, causing valvular insufficiency. A patient in whom aortitis produced valvular masses, with aortic and peripheral arterial aneurysms, embolic episodes and aortic insufficiency is described. Valve replacement for suspected infective endocarditis was complicated by homograft dehiscence and multiple false aneurysms. Although immunosuppression was successful in decreasing the patient's vasculitis, he became infected and died of complications of aspergillus infection.

Bacterial pericarditis after heart transplantation: successful management of two cases with catheter drainage and antibiotics.

OBJECTIVE: To describe the diagnosis and management of bacterial pericarditis after heart transplantation. PATIENTS AND METHODS: Two patients with Staphylococcus aureus pericarditis after heart transplantation were successfully treated conservatively with closed catheter drainage and antibiotics. RESULTS: The patients were alive three and six years, respectively, following surgery. At follow-up, right heart catheterization demonstrated normal hemodynamics in one patient and a pattern of constrictive pericarditis in the other patient which was man-aged with furosemide. CONCLUSIONS: Conservative management of bacterial pericarditis by closed catheter drainage and antibiotics can be considered in selected patients after heart transplantation.

Prospective, randomized comparison of intravenous and oral ciprofloxacin with intravenous ceftazidime in the treatment of nosocomial pneumonia.

OBJECTIVE: To compare the efficacy of intravenous and oral ciprofloxacin and intravenous ceftazidime in the treatment of nosocomial pneumonia. DESIGN: Randomized, nonblinded, multicentre comparative trial. SETTING: Seven Canadian university hospitals. POPULATION: Adult patients with moderate to severe pneumonia developing 72 h or longer after hospitalization. METHODS: After informed consent was obtained, patients were randomized to receive intravenous ciprofloxacin 300 mg every 12 h or ceftazidime 2 g every 8 h. After three days, patients in the ciprofloxacin arm could be switched to oral ciprofloxacin, 750 mg every 12 h. Concomitant clindamycin was allowed for three days in patients with syndromes consistent with Gram-positive or anaerobic infection. Erythromycin could be used if cultures revealed no pathogen. RESULTS: A total of 149 patients were enrolled, of whom 124 were eligible for efficacy analysis. Of 119 pathogens identified in 87 patients, 84 were Gram-negative, and 35 Gram-positive. The mean duration of ciprofloxacin therapy was 12.1 days, of which 9.2 days were given intravenously. Ceftazidime was given for a mean of 9.8 days. There was eradication or reduction of pathogens in 75.7% of ciprofloxacin patients and 70.6% of the ceftazidime group. Clinical resolution or improvement occurred in 87.1% of ciprofloxacin recipients and 87.3% of the ceftazidime group. Eight ciprofloxacin and six ceftazidime patients died. Overall outcomes were considered to be successful in 85.2% of ciprofloxacin patients and 87.1% of ceftazidime recipients. Adverse events were mild. CONCLUSIONS: There were similar efficacy and safety of intravenous and oral ciprofloxacin and intravenous ceftazidime in the treatment of patients with hospital-acquired pneumonia. Physicians were reluctant to use oral therapy in patients.

Whipple's disease with constrictive pericarditis: a rare disease with a rare presentation.

Whipple's disease is a multisystem disease that can affect the heart with predominantly endocardial and pericardial involvement and, less often, myocardial inflammation. Previously diagnosed at autopsy, cardiac involvement in Whipple's disease is being recognized clinically more often. A 58-year-old man with Whipple's-related constrictive pericarditis, arthralgias and lymphadenopathy is described. He underwent antibiotic treatment and pericardiectomy with improvement in his clinical state.

Barriers to the effective management of respiratory tract infections in the community.

The treatment of respiratory tract infections (RTIs) continues to challenge the knowledgeable and conscientious physician. Upper RTIs such as sinusitis and tonsillitis/pharyngitis - while not generally life-threatening - are associated with personal cost and suffering, while infections of the lower respiratory tract, including community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB), represent a more serious clinical challenge and account for almost half of all community-acquired infections. Moreover, such infections may be fatal. Laboratory tests for etiologic agents of RTIs are often insensitive and slow and identify the causative pathogen in only a minority of cases. Therapy for RTIs is, therefore, generally presumptive and instituted before there is a clear understanding of etiology. Such an approach requires antibacterials that possess a spectrum of activity which covers both the common and atypical/intracellular pathogens associated with RTIs to enable physicians to confidently prescribe treatment. A major barrier to the confident prescribing of empiric therapies for RTIs is the increasing prevalence of resistance to existing antibacterial agents among respiratory tract pathogens. Increasing levels of antibacterial resistance now threaten the utility of existing agents, primarily the beta-lactams and macrolides, and continue to drive the search for newer agents which retain activity against drug-resistant respiratory tract pathogens. This need is emphasized by recent evidence that bacterial resistance may be associated with poorer clinical outcomes, particularly for patients with severe infections. There is enormous concern and uncertainty about the factors that contribute to increasing bacterial resistance and treatment strategies that should be adopted to minimize this problem. The arguments have raged particularly around recent Infectious Diseases Society of America (IDSA) guidelines on the treatment of CAP, which have advocated a greater role for fluoroquinolones. One school of thought - driven in part by concerns over cost of therapy - advocates the use of older agents such as amoxicillin, in the hope that any resistance that is incurred will be to these agents, leaving the newer agents for select cases with acquired resistance. Advocates of the newer agents argue that this approach represents a false economy and that there is a greater likelihood of first-line success with newer agents, so that patients are less likely to require a second physician visit and a second course of antibacterial therapy.

Antimicrobial drug susceptibility of respiratory isolates of Hemophilus influenzae from adults.

Hemophilus influenzae isolates from sputum of 111 patients with chronic bronchitis were tested for susceptibility to 8 antimicrobial drugs. A new beta-lactam, LY-127935, was the most active agent tested. Ampicillin, cefamandole, tetracycline, and cefuroxime showed good activity against most isolates. Two strains, both nontypable, were resistant to ampicillin and produced beta-lactamase. Cefaclor was somewhat less effective, although most strains were susceptible. Erythromycin and cephalexin were of limited utility.

Adverse reaction to mefloquine associated with ethanol ingestion.

A 40-year-old man with no history of neuropsychiatric illness was taking one 250-mg tablet of mefloquine (MFQ) weekly for malaria prophylaxis while in Tanzania. He experienced no adverse reaction in association with his first two doses. Concurrently with both his third and his fourth dose he consumed about half a litre of whisky. On both occasions he experienced hallucinations, paranoid delusions and suicidal ideation. Thereafter he continued taking the MFQ, abstained completely from ethanol ingestion and had no recurrence of psychiatric symptoms. It is hypothesized that the combination of MFQ and ethanol caused the two episodes of severe psychiatric disturbance.

Induction of the in vitro anti-HBs response by hepatitis B surface antigen.

The production in vitro of antibody to hepatitis B surface antigen by peripheral blood mononuclear cells of healthy volunteers was studied after each of the three doses of hepatitis B vaccine. An in vitro hepatitis B surface antigen antibody response was successfully induced in 12% of the specimens taken over a 7 month period. The response to this antigen was induced in additional samples if cells had been treated previously with anti-CD4 and complement or anti-CD8 and complement prior to culture initiation. The addition of interleukin 2 could also induce the formation of antibodies to hepatitis B surface antigen. The results suggest that the antibody response to hepatitis B surface antigen is complex and varies depending on the individual and time of sampling.

Colitis associated with metronidazole therapy.

A 46-year-old woman was treated with oral metronidazole for trichomonal vaginitis and developed diarrhea, which persisted for five weeks. Tissue culture assay of stool supernatant showed a cytopathic toxin that was neutralized by Clostridium sordellii antitoxin, and cultures yielded Clostridium difficile, which produced a similar or identical cytotoxin in vitro. This isolate proved sensitive to metronidazole at 0.25 microgram/ml. Prior reports have indicated that metronidazole may also be used therapeutically in patients with antibiotic-associated colitis ascribed to other agents. The patient presented here shows the enigma that the same agent used for therapy of colitis may also cause this complication.

Nosocomial gram-negative parotitis.

Nosocomial parotitis is an uncommon postoperative complication, usually affecting elderly, debilitated, dehydrated patients. The preponderance of gram-positive pathogens has been emphasized. The authors present two cases of gram-negative parotitis and review the literature on this condition. Because the organisms producing nosocomial infection in patients receiving intensive care are commonly gram-negative bacilli, treatment should be based on the findings of Gram's staining of the pus obtained from Stensen's duct, altered when necessary by the final culture results.

Superoxol(catalase)test for identification of Neisseria gonorrhoeae.

The Superoxol (Merck & Co., Inc., Rahway, N.J.) test (catalase test using 30% H2O2) was used to differentiate Neisseria gonorrhoeae from other Neisseria species. A positive test was defined as immediate, brisk bubbling upon dropping 30% H2O2 onto a bacterial colony. One hundred percent of the gonococci were Superoxol positive. Only 1% of Superoxol-positive isolates on Thayer-Martin agar were organisms other than gonococci (99% specificity). The test was more reliable than the coagglutination test. Individual strains of a wide variety of Neisseria and Branhamella species were Superoxol positive. They could usually be differentiated from N. gonorrhoeae by their poor growth on selective media, colonial morphology on nonselective media, and simple biochemical tests. The Superoxol test is an excellent screening test for N. gonorrhoeae. A positive result on a clinical isolate growing on Thayer-Martin agar is strongly suggestive of the presence of gonococci.

Humoral and cellular immune responses by normal individuals to hepatitis B surface antigen vaccination.

The kinetics of the cellular and humoral responses of 30 recipients of hepatitis B vaccine were studied. All individuals exerted an HBsAg blastogenic response sometime throughout the study period but the maximum response was detected on day 28 and 56. The removal of CD8+ cells enhanced significantly the HBsAg response at the times tested, whereas treatment with anti-CD4, anti-CD8, C' and anti-CD4+ C' had no effect. Vaccination also led to the depression of phytohaemagglutinin (PHA) blastogenic response. This response was maximally suppressed 4 to 8 days after immunization at least for the primary and secondary responses and 28 days after the third dose of vaccine. The humoral response to HBsAg was detected only after the second dose of vaccine was given. The results suggest that a CD8+ cell controls the magnitude and intensity of the HBsAg blastogenic response, which may help to explain why several investigators had not been able to detect this response in hyperimmunized individuals. Primary immunization with HBsAg does lead to an expansion of B memory since a secondary response anti-HBsAg was observed.

Phytohemagglutinin mitogenic response of normal individuals vaccinated with hepatitis B vaccine.

The phytohemagglutinin (PHA) blastogenic response of normal healthy individuals was studied before and after vaccination with hepatitis B surface antigen. The PHA response was suppressed 2 d after the first dose of vaccine but was not affected by the second and the third doses of vaccine. The suppressed PHA blastogenic response on day 7 was not enhanced by the addition of interleukin-2 or indomethacin even though an increase in cell number expressing CD25 was observed. The removal of CD4+ or CD8+ cells enhanced the PHA response but only on days 2 or 4 and not at other sampling times, which suggests that the suppression is mediated by CD4+ or CD8+ cells. The addition of interleukin-2 alone or with PHA did not reverse the suppression at any time tested. In vitro induction of suppressor cells was performed and was blocked by the addition of indomethacin at the time of culture initiation.

Antibiotic prophylaxis in head and neck cancer surgery.

A randomized, placebo-controlled, double-blinded trial of cefamandole in the prophylaxis of infection after major head and neck surgery was performed. Patients were given the drug on call to the operating room, and again four and eight hours after the initial dose. Twenty of 25 patients were evaluable. Wound infection developed in five of nine placebo recipients (55%), and three of 11 (33%) receiving cefamandole. Mean duration of hospitalization was 91.1 days in the placebo group, 34.3 in the cefamandole group (p less than 0.05). The study was stopped because of excessive morbidity in the placebo group. Cefamandole decreases the duration of hospitalization following major head and neck cancer surgery.

Bacitracin treatment of antibiotic-associated colitis and diarrhea caused by Clostridium difficile toxin.

Four cases of antibiotic-associated colitis and diarrhea caused by Clostridium difficile were successfully treated with oral bacitracin, 25,000 units four times daily for 7-10 days. Diarrhea resolved in all of the cases, in 2 days, with disappearance of Clostridium difficile toxin in the stools in 3 out of 4 patients so measured. Two of the patients treated had relapses after vancomycin, while the other 2 were experiencing the first episodes. One patient relapsed after bacitracin treatment, but was treated successfully with vancomycin. Our preliminary experience indicates that bacitracin, being less expensive and more readily available world-wide than vancomycin, could be used as an alternative drug for toxin-induced colitis or diarrhea.