Impact of treating Staphylococcus aureus nasal carriers on wound infections in cardiac surgery.

Staphylococcus aureus is a common cause of postoperative wound infections, and nasal colonization by this organism is an important factor in the development of infections. Treatment with mupirocin can eradicate the organism in the short term, and prophylactic treatment of colonized patients may prevent postoperative S. aureus infections. A double-blind, randomized, placebo-controlled trial was performed to determine whether nasal mupirocin administered pre-operatively to S. aureus carriers reduces the rates of sternal and leg wound infections after cardiac surgery. The study enrolled 263 patients with nasal S. aureus undergoing elective cardiac surgery at St. Michael's Hospital, Toronto, Canada. Patients were assessed for infections in the immediate postoperative period and two months later. Two hundred and fifty-seven patients were included in the intention-to-treat analysis and re-analysed according to the actual treatment applied. Wound infections occurred in 17 (13.5%) mupirocin recipients and 11 (9.1%) placebo recipients (P=0.319), with seven (5.4%) and six (4.7%) sternal infections, respectively. Two (1.6%) wound infections were acquired postoperatively in the mupirocin group, neither of which were caused by S. aureus. The placebo group had three (2.4%) nosocomial wound infections, with two (1.6%) S. aureus bacteraemias (P=0.243). Among patients receiving mupirocin, 106 (81.5%) cleared S. aureus compared with 59 (46.5%) patients receiving placebo (P<0.0001). There was no significant difference between intention-to-treat and actual treatment groups. Prophylactic intranasal mupirocin administered to S. aureus carriers did not reduce the rates of overall surgical site infections by S. aureus, and only showed a trend towards decreased incidence of nosocomial S. aureus infections.

Cardiac involvement in human immunodeficiency virus-infected patients.

Heart involvement in patients with AIDS has been described in autopsy and clinical series, but the true incidence in HIV-infected patients is not clear. A prospective study was done on 101 unselected HIV-infected patients (71 with AIDS and 30 with pre-AIDS) and 24 healthy controls to assess the prevalence of cardiac abnormalities. Assessment included physical examination, electrocardiogram, two-dimensional echocardiogram, and Doppler studies. At least one abnormality was detected in 41 (40.6%) HIV-infected patients vs. 3 (12.5%) in controls (p = 0.003). Echocardiographic abnormalities were detected in 29 (28.7%) HIV-infected patients and 3 (12.5%) controls (p = 0.04). There were no significant differences in abnormalities on physical examination, electrocardiogram, or Doppler studies. Only six (5.9%) HIV-infected patients had abnormal cardiac findings on physical examination. We found no correlation between HIV staging, CD4 cell count, acute illness, or severity of illness and the presence of cardiac abnormalities. Cardiac abnormalities in HIV-infected patients are more frequent than in healthy controls, but most abnormalities are of no significant clinical consequence.

Escherichia coli emphysematous endophthalmitis and pyelonephritis. Case report and review of the literature.

Emphysematous escherichia coli endophthalmitis occurred in a 72-year-old patient as a complication of E. coli septicemia secondary to emphysematous pyelonephritis and endocarditis. This is the first reported case of endogenous emphysematous endophthalmitis secondary to E. coli septicemia.

Treatment of nongonococcal urethritis with ciprofloxacin.

A randomized, double-blind study was performed in 225 men with nongonococcal urethritis or postgonococcal urethritis, in which the efficacy of ciprofloxacin (750 mg twice daily for seven days) was compared with that of doxycycline (100 mg twice daily for seven days). Of the 145 evaluable patients completing three weeks or more of follow-up or reaching an end point, 74 patients received doxycycline and 71 received ciprofloxacin. Chlamydia trachomatis and mixed infections with Ureaplasma urealyticum were more frequent in the cip, ofloxacin group, but the differences were not significant. The overall cure rates were similar for the two regimens (52.1 percent for ciprofloxacin and 60.8 percent for doxycycline; p greater than 0.3). However, in patients with chlamydial infections alone, ciprofloxacin was significantly less effective than doxycycline (45.5 percent versus 75 percent; p = 0.04). In patients with U. urealyticum infections alone, there was a more favorable trend in the ciprofloxacin group (69.2 percent versus 45 percent; p = 0.12). In patients whose culture results were negative, the responses were very similar (60.9 percent for ciprofloxacin and 64.3 percent for doxycycline). Both drugs were well tolerated; side effects, which were mostly gastrointestinal in nature, were mild.

Active immunization of patients with HIV infection: a study of the effect of VaxSyn, a recombinant HIV envelope subunit vaccine, on progression of immunodeficiency.

Infection with the human immunodeficiency virus (HIV) leads to a progressive immunodeficiency characterized by decreasing levels of CD4+ T lymphocytes. VaxSyn, a vaccine based on the recombinant envelope glycoprotein subunit (rgp160) of HIV-1IIIB, was used to immunize HIV-infected patients to determine whether its administration was beneficial with respect to slowing disease progression. A 3-year multicenter, randomized, placebo-controlled, double-blinded, efficacy and safety trial of repeated immunization with VaxSyn was used to evaluate the long-term impact on the progression of immunodeficiency. VaxSyn in alum, or alum alone, was given to 278 HIV-infected asymptomatic individuals with initial CD4 counts of > or =500 cells/mm3. Clinical findings, the CD4 count, and both virological and immunological parameters were followed. No significant differences were observed between the treatment and placebo control groups in rate of CD4 T cell decline, time to initiation of antiretroviral therapy, incidence of opportunistic infections, HIV RNA plasma viremia, HIV viral infectivity as measured by quantitative HIV coculture assay, and death. This study revealed no effect on either clinical or laboratory virological parameters from the administration of VaxSyn.

The value of prophylactic antibiotics in aorat-coronary bypass operations: a double-blind randomized trial.

Prospective and retrospective studies were performed to determine the efficacy of prophylactic antibiotics in preventing infections in patients undergoing arota-coronary bypass. One-hundred five patients were randomized in a double-blind fashion to receive either methicillin or saline-placebo for 3 days. The over-all infection rate was 26.7% with 48.9% in the control group and 8.6% in the methicillin group (p less than 0.001). Significant sternal wound infection developed in 21.3% of the control group and 0% of the methicillin group (p less than 0.01). Staphylococcus aureus was the predominant organism causing significant sternal infection (methicillin group versus control group, 5.2% and 21.3%; p less than 0.05). The length of postoperative stay in hospital and the number of days with fever was significantly greater in the control group than in the methicillin group (p less than 0.001). During the same period of time, 160 patients were studied retrospectively. Of these, 150 patients received cephalothin prophylaxis and 10 received methicillin. Comparison of the rates of infection in the cephalothin group to the total methicillin group (prospective and retrospective) showed no significant difference. The study clearly demonstrated that a short course of prophylactic antistaphlococcal penicillin or cephalosporin is justified in aorta-coronary bypass.

Psychosocial aspects of chronic, clinically unconfirmed vulvovaginitis.

Women with chronic symptoms of vulvovaginitis referred to a university vulvovaginitis clinic were assessed on psychological and social (including sexual) variables to determine whether differences existed among women with unconfirmed vulvovaginitis, women with confirmed vulvovaginitis, and healthy controls. Eighty-three consecutive women with chronic symptoms of vulvovaginitis and 32 asymptomatic control women completed clinical examinations, cultures, and the following psychological tests or questionnaires: the Brief Symptom Inventory, the Center for Epidemiologic Studies--Depression Scale, the Dyadic Adjustment Scale, a sexual behavior and response questionnaire (Campion), and a study questionnaire. Statistical analyses (chi 2 and analysis of variance) were performed on the confirmed and unconfirmed vulvovaginitis and control groups of women. Women with confirmed and unconfirmed vulvovaginitis scored higher than control women on several psychological variables, but women with unconfirmed vulvovaginitis were found to be significantly more emotionally distressed on psychological tests and to report more discomfort during sexual intercourse than both women with confirmed vulvovaginitis and healthy controls. Psychosocial inquiry is important in the clinical assessment and management of such women.

Pharmacokinetics of fluconazole in serum and cerebrospinal fluid in a patient with AIDS and cryptococcal meningitis.

The detailed pharmacokinetics of fluconazole in serum and cerebrospinal fluid (CSF) were studied in a patient with acquired immunodeficiency syndrome and cryptococcal meningitis, after an intravenous dose of 400 mg. Fluconazole exhibited a serum elimination half-life of 34.2 hours, distribution volume of 0.56 L/kg, and clearance of 0.19 ml/min/kg. Peak CSF concentration occurred at 4 hours after the dose. Overall penetration of fluconazole based on the ratio of areas under the curve of CSF to serum was 70%. The drug exhibited an excellent pharmacokinetic profile for treatment of central nervous system fungal infections.

Clinical and cost considerations in the pharmacotherapy of vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is a frequent cause of morbidity in women of reproductive age. Most women will experience 1 or 2 episodes in their lifetime, but a smaller population develop chronic recurrent disease. There are few data on cost or pharmacoeconomic considerations in the management of this condition. The disease does not usually result in long term disability, loss of employment or death, but could affect a woman's work performance through irritability, frustration and unhappiness. This review attempts to estimate the least costly programme or regimen (as the efficacy of different regimens is similar) that would be applicable to patients, third-party payers and society. Nonprescription or over-the-counter (OTC) antifungal preparations could have an impact on overall cost in the management of VVC. In the management of infrequent acute VVC, an OTC preparation would be least costly to the healthcare system (provided that the diagnosis was correct). The strategies used to control symptoms in patients with chronic recurrent VVC should be based on the frequency of recurrent episodes. For patients with less than 12 episodes a year, empirical self-treatment at the onset of symptoms with an OTC agent (e.g. intravaginal clotrimazole 500mg) is less costly and preferable to patients than monthly prophylaxis. Patients with a greater frequency of recurrences may benefit from monthly, daily or twice weekly prophylaxis. At present, for very frequent recurrences, intravaginal clotrimazole 200mg twice weekly appears to be as effective as daily oral ketoconazole, and may be safer and less costly. However, because of the lack of prospective controlled studies, most of these recommendations are based on hypothetical reasonings. Furthermore, the disadvantages of OTC antifungals include the potential for overuse and inappropriate use, possibly resulting in the delayed diagnosis and treatment of other conditions. On balance, OTC preparations may provide patients with faster and more economical care, and improve healthcare delivery.

Case report: treatment of blastomycosis with fluconazole.

The authors present two cases of systemic blastomycosis successfully treated with fluconazole. In one case, the disease involved the respiratory tract, and the central nervous system was presumed to be involved. The second case consisted only of pulmonary blastomycosis. Both patients were treated with oral fluconazole 200 mg twice per day for 9 and 6 months, respectively. Treatment with this new triazole antifungal agent resulted in the complete resolution of the disease in both patients. They have remained asymptomatic for more than 6 months after the completion of therapy.

Poor response to oral ciprofloxacin in the treatment of peritonitis in patients on intermittent peritoneal dialysis.

OBJECTIVES: To assess the clinical value of oral ciprofloxacin in the treatment of peritonitis in an intermittent peritoneal dialysis (IPD) population. DESIGN: Open nonrandomized prospective study. SETTING: Nephrology Peritoneal Dialysis Unit in a tertiary care, teaching hospital of the University of Toronto. PATIENTS: Subjects were participants of the IPD program with an acute episode of peritonitis defined as at least two of the following: 1. signs and symptoms of peritonitis, 2. cloudy peritoneal fluid with a white blood cell count of > 100/microL, 3. demonstration of bacteria in peritoneal effluent by gram stain or culture. Ten patients were enrolled in the study, but two were withdrawn because of side effects and growth of a resistant bacteria. INTERVENTIONS: Ciprofloxacin 750 mg po q12h for 2 doses, then 750 mg daily or 500 mg twice daily for 10 days. MAIN OUTCOME MEASURES: Efficacy was determined by clinical and microbiological assessment. Cure was defined as resolution of signs and symptoms with eradication of the causative organism. Peritoneal effluent and blood samples were analyzed for ciprofloxacin concentration. RESULTS: Ciprofloxacin was effective in treating only one of ten episodes of peritonitis. Seven patients were defined as microbiological failures (persistence or relapse of organisms). The signs and symptoms of peritonitis improved in 2 patients, but the remaining 5 failed clinically. Only Gram-positive organisms were cultured. CONCLUSIONS: Ciprofloxacin cannot be recommended for the treatment of intermittent peritoneal dialysis-related Gram-positive bacterial peritonitis.

Medication use patterns in HIV-positive patients.

Patients with HIV infection or AIDS often receive several medications for treatment or prevention of their primary disease and/or associated complications. The objective of this study was to document patterns of drug use in an HIV-positive, outpatient population. Data were collected via one-on-one interviews with 26 HIV-positive patients; prescription and non-prescription drug use, adverse drug reactions and drug allergies were recorded. Anti-retroviral therapy was received by over 90 % of the patients. Over 90% of patients were on anti-infective agents, commonly cotrimoxazole or dapsone, while 27% received acyclovir. At least 70% of patients used three or more prescription medications concurrently. Every patient reported self-medicating with at least one over-the-counter (OTC) product and over half used three or more OTC products concurrently. Adverse reactions, mainly attributable to zidovudine, were reported by over 80% of patients. Non-compliance was a common drug-related issue; over 70% of patients omitted drug doses. In conclusion, the use of multiple medications in the ambulatory HIV-positive patients presents the health care team with potential drug-related problems that may ultimately affect the efficacy and toxicity of therapy. Thus pharmacists may play an active role in the provision of direct care to these patients.

Bacterial meningitis in HIV-infected patients: Case reports and review of the literature.

Meningitis is not an uncommon complication of the acquired immune deficiency syndrome. Purulent meningitis is not a well recognized infection in human immunodeficiency virus (HIV) positive patients. Three cases of bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis and Listeria monocytogenes are presented. These cases illustrate that common community organisms may present in HIV positive patients. An acquired B cell defect may predispose to bacterial infections responsible for meningitis in HIV-infected patients.

Stool examination and reports in the traveller.

Diarrhea is by far the most common illness in a returning traveller, so family physicians frequently request stool examination for these patients. Appropriate history and adequate specimens, obtained on three or four different days, are crucial to proper interpretation of results. Decisions on treatment will depend on the patient's current symptoms and type of pathogen. Not all pathogens require treatment and not all reported parasites are pathogenic. The patient's lifestyle and occupation may influence decision-making on treatment of asymptomatic carriers of certain parasites or bacterial intestinal pathogens. Guidelines for such decision-making are presented.

Prevention of haemodialysis and peritoneal dialysis catheter related infection by topical povidone-iodine.

Catheter related sepsis, especially with staphylococci, is one of the most important complications of haemodialysis or peritoneal dialysis. In a prospective, randomized, open study of 129 haemodialysis patients, exit site infection and bacteraemia were significantly greater in the untreated group (18.2% each) than the group treated with povidone-iodine (PVP-I) ointment (4.8% each), P < 0.02. In nasal carriers of S. aureus, PVP-I resulted in 100% risk reduction of bacteraemia and exit site infection (P < 0.05) and 70% risk reduction of catheter tip infections (P < 0.05). Preliminary results of an on-going randomized study in patients on intermittent peritoneal dialysis suggest, in the 69 patients so far studied, a reduced S. aureus infection rate in patients who received PVP-I ointment at the catheter exit site (2.9%) compared with the untreated group (8.8%) despite a higher nasal carriage rate in the PVP-I group. Statistical significance has not been demonstrated for these interim results and the study is continuing.

The role of fluoroquinolones in the management of skin, soft tissue, and bone infections.

The fluoroquinolones are a group of potent antimicrobials with marked in vitro activity against gram negative bacteria and, to a lesser extent, staphylococci. Their major advantages include the availability of oral preparations, relative safety, and excellent tissue penetration. Controlled clinical studies have shown that the oral quinolones are as effective as cephalexin in mild skin and soft tissue infections, and that ciprofloxacin is as effective as cefotaxime in more severe infections. Uncontrolled studies chiefly with ciprofloxacin in patients with acute and chronic osteomyelitis with staphylococci and gram negative bacteria have resulted in cure rates of 60-85%. The quinolones offer definite advances in the management of gram negative osteomyelitis and could be substituted for the aminoglycosides or third generation cephalosporins in nosocomial soft tissue infections. However, the quinolones offer no advantage over standard therapy for mild skin and soft tissue infections, particularly those caused by streptococci or methicillin-sensitive staphylococci. Development of resistant mutants may become a problem with indiscriminate use of these agents.

The rectal carriage of yeast in patients with vaginal candidiasis.

Reinfection from the lower gastrointestinal tract is a possible source of recurrent vulvo-vaginal candidiasis. A prospective study to assess the prevalence of yeast carriage in various orifices (including the rectum) in controls and patients, and the relationship to acute vaginitis, was conducted. Cultures for yeast were obtained from the mouth, rectum, vulva, and vagina every 1-2 months for 1 y from the patients. The prevalence of yeast carriage in healthy controls was 3/37 (8.1%) from the vulva, vagina, and rectum, and 4/37 (10.8%) from the mouth. In patients, yeast carriage during episodes of vaginitis was: from the vagina, 190/193 (98.4%); from the vulva, 107/193 (55.4%); from the rectum, 93/193 (48.2%); and from the mouth, 52/193 (26.9%). During visits without vaginitis, yeast carriage was lower: in the rectum, 59/587 (10.1%); in the vulva, 53/459 (11.6%); in the vagina, 77/587 (13.1%); and in the mouth, 89/587 (15.2%). Yeast in the lower bowel during symptomatic vaginitis is higher (p = 0.0001) than in controls, but not significantly greater during asymptomatic periods. Recurrence of Candida vaginitis is not dependent on yeast reservoir in the lower gut between symptomatic episodes.

Single-dose therapy of infectious diseases.

Single-dose antimicrobial therapy has clear advantages over multiple-dose therapy. Long-acting penicillins have been used for many years in single doses for treatment of streptococcal pharyngitis and early syphilis. More recently, shorter-acting agents are used for non-invasive mucosal infections. In trichomonas vaginitis, for instance, a 2g single dose of metronidazole is approximately 92% effective and is considered the treatment of choice. Controversy still exists about the value of single-dose therapy in women who have bacterial cystitis. However, there is good evidence that 2 or 3 double-strength tablets of co-trimoxazole are very effective and safe in the treatment of uncomplicated cystitis in healthy women.

The value of treating the sexual partners of women with recurrent vaginal candidiasis with ketoconazole.

OBJECTIVE: To determine whether treatment of the sexual partners of women with chronic vulvovaginal candidiasis with oral ketoconazole can reduce the recurrence rate of candida vaginitis. DESIGN: Single blind randomised study where all the women were treated with ketoconazole 400 mg daily for 7 days after an acute episode of candida vaginitis and half the male partners were treated with ketoconazole 200 mg daily for 5 days. SETTING: Women's Candida Clinic of St. Michael's Hospital, a University of Toronto teaching Hospital, Toronto, Ontario, Canada. SUBJECTS: Fifty-four women attending the clinic with at least four proven episodes of candida vaginitis and their male sex partners (stable monogamous relationships) were enrolled in the study. MAIN OUTCOME MEASURES: Clinical recurrence of candida vaginitis with confirmation by smear and culture. Follow-up was obtained one to two weeks after initial treatment, then monthly for one year. RESULTS: In the control group (untreated partners), 20 of 28 (71%) patients had recurrences in six months, versus 17 of 26 (65%) patients in the treated group (treated partners) (95% Confidence Interval (CI) for the difference in recurrence rate = -19% to 31%). At one year, 23 of 28 (82%) patients in the control group had recurrences, versus 22 of 26 (85%) in the treated group (CI = -23% to 17%). CONCLUSION: Treatment of the male partners, with a brief course of ketoconazole, is not of value in reducing the incidence of relapse in women with recurrent vaginal candidiasis. It is unlikely that a larger study would show a clinical important difference.

The value of chronic suppressive therapy with itraconazole versus clotrimazole in women with recurrent vaginal candidiasis.

OBJECTIVE: To determine the comparative efficacy of oral itraconazole versus intravaginal clotrimazole in suppressing recurrent episodes of vulvovaginal candidiasis. DESIGN: Prospective randomised open study of women with recurrent vulvovaginal candidiasis. Clinical and microbiological assessments were made monthly for 12 months. SETTING: Women's Clinic of a University teaching hospital. SUBJECTS: Forty-four otherwise healthy, non-pregnant women, with at least four proven episodes of candida vaginitis in the last year were enrolled into the study. INTERVENTION: After an acute episode of candida vaginitis, 22 women received oral itraconazole 200 mg daily for five days, then 200 mg twice weekly for six months; and 22 women received intra-vaginal clotrimazole 200 mg ovules daily for five days, then 200 mg twice weekly for six months. MAIN OUTCOME MEASURES: Symptomatic recurrent clinical vulvovaginal candidiasis during the first six months of suppressive therapy was the major endpoint. A secondary endpoint was recurrent candida vaginitis within six months after completion of therapy. RESULTS: Six patients did not complete the study, one in the itraconazole group and five in the clotrimazole group. Of the evaluable patients, seven of 21 patients (33.3%) in the itraconazole group versus none (0%) of 17 patients on clotrimazole were failures on suppressive therapy, p = 0.02. Following discontinuation of suppressive therapy, recurrences of candida vaginitis were similar, 10 (47.6%) of patients on itraconazole (95% confidence interval (CI) 27-67%), versus 11 (64%) patients on clotrimazole (CI 41-87%), p = 0.15. CONCLUSION: Intermittent suppressive therapy with clotrimazole was more effective than itraconazole in preventing recurrent candida vaginitis, provided patients adhered to the regimen. Recurrence of vaginitis was common with both regimens after stopping suppressive therapy.