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.

Sputum versus bronchoscopy for diagnosis of Pseudomonas aeruginosa biofilms in cystic fibrosis.

The present authors hypothesised that bronchoscopy with protected specimen brush may sample biofilm-forming bacteria adherent to the airway wall, whereas traditional sputum collection may not. Pseudomonas aeruginosa obtained from sputum, bronchoalveolar lavage and protected brush, taken from the right upper lung bronchus of 12 adult patients with cystic fibrosis, were compared. Retrieved bacteria were genotyped, and grown in planktonic cultures and as biofilms, and susceptibilities to individual antibiotics and to antibiotic combinations were determined. Bacterial cultures obtained using bronchoscopy did not yield any new strains of bacteria that were not also found in sputum. A total of 10 patients (83%) had a single strain of P. aeruginosa found using sputum, bronchoalveolar lavage and protected brush techniques, and two patients (17%) had two strains recovered in sputum, but only one strain was recovered using bronchoscopic techniques. Susceptibility to single antibiotics and to antibiotic combinations were not different between planktonically or biofilm-grown bacteria derived from sputum, as compared to those obtained by bronchoalveolar lavage and protected brush. In conclusion, sputum collection provides as much information as bronchoscopy for characterising the genotype and antibiotic susceptibility of chronic Pseudomonas aeruginosa infection in patients with stable cystic fibrosis.

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.

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.

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.

Treatment of community-acquired pneumonia in the elderly: the role of cefepime, a fourth-generation cephalosporin.

In a prospective, multicentre double-blind trial, 151 patients over the age of 65 years were randomly assigned to receive either cefepime 2 g every 12 h for a minimum of 3 days and up to 14 days or ceftriaxone 1 g every 12 h for a minimum of 3 days and up to 14 days. Antibiotics were maintained until 48 h after fever had resolved; no other antibiotics were permitted. The average age in each group exceeded 77 years and significant co-morbidity was found in the majority of patients. The mean total duration of therapy was 5.8+/-2.4 days for the cefepime group and 6.7+/-2.7 days for the ceftriaxone group (P = 0.06). The clinical success rate at the end of therapy was 79.1% with cefepime and 75.4% with ceftriaxone (P = 0.62). At the end of follow-up, 91.7% of the cefepime-treated patients and 86.5% of the ceftriaxone patients had a satisfactory clinical response (P = 0.38). In 35 bacteriological evaluable patients, potential pathogens were eradicated in all but one patient receiving cefepime. Seven patients in each group died during the study period but in each case the death was unrelated to study drug. The commonest side-effect was diarrhoea (cefepime, five patients; ceftriaxone, two patients). The clinical and microbiological efficacy of cefepime is similar to that of ceftriaxone in elderly patients with community-acquired pneumonia requiring hospitalization. Cefepime is an appropriate choice for the treatment of community-acquired respiratory tract infections in the elderly.

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.

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.

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.

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.

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.

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.

Concentrations of teicoplanin in serum and atrial appendages of patients undergoing cardiac surgery.

The concentrations of teicoplanin in sera and heart tissues of 49 patients undergoing coronary bypass were measured. Each patient received a 6- or 12-mg/kg dose of teicoplanin administered in a slow intravenous bolus injection over 3 to 5 min beginning at the time of induction of anesthesia. Mean +/- standard error of the mean concentrations in serum were, for the two doses, respectively, 58.1 +/- 1.7 and 123.3 +/- 7.4 micrograms/ml 5 min after administration and 22.2 +/- 0.7 and 56.5 +/- 2.8 micrograms/ml at the time of removal of atrial appendages. Mean +/- standard error of the mean concentrations in tissue were 70.6 +/- 1.7 and 139.8 +/- 2.2 micrograms/g, respectively, giving mean tissue/serum ratios of 3.7 +/- 0.3 and 2.8 +/- 0.2, respectively. Teicoplanin penetrates heart tissue readily and reaches levels in the serum far in excess of the MICs for most pathogens that have been found to cause infections following open heart surgery.

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.

Once-daily therapy with ceftriaxone compared with daily multiple-dose therapy with cefotaxime for serious bacterial infections: a randomized, double-blind study.

A randomized, double-blind study was done to compare the efficacy and toxicity of daily single-dose therapy with intravenous ceftriaxone (2 g every 24 h) with daily multiple-dose therapy with cefotaxime (2 g every 6 h) for treatment of serious bacterial infections in nonneutropenic patients. Of the 325 patients who were evaluable for toxicity, 241 (74.2%) were evaluable for efficacy. Infection sites included lung (106), urinary tract (42), skin and soft tissue (43), bone and joint (23), bacteremia (21), and hepatobiliary (5). Definite infections were present in 173 cases (71.8%) and possible infections in 68 (28.2%). Analysis of clinical and bacteriologic responses and adverse drug reactions showed no significant differences between the regimens. Values for 95% confidence limits on the differences between regimens for positive clinical and bacteriological outcomes in definite infections were -0.8% to 3.0% and -1.9% to 9.1%, respectively. Thus, daily single-dose therapy with ceftriaxone was comparable to daily multiple-dose therapy with cefotaxime in treating these bacterial infections.

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.

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.