Placebo found equivalent to amoxicillin for treatment of acute bronchitis in Nairobi, Kenya: a triple blind, randomised, equivalence trial.

BACKGROUND: Antibiotic treatment is not recommended for acute bronchitis in immunocompetent patients in industrialised countries. Whether these recommendations are relevant to the developing world and to immunocompromised patients is unknown. DESIGN, SETTING AND PARTICIPANTS: Randomised, triple blind, placebo controlled equivalence trial of amoxicillin compared with placebo in 660 adults presenting to two outpatient clinics in Nairobi, Kenya, with acute bronchitis but without evidence of chronic lung disease. MAIN OUTCOME MEASURE: The primary study end point was clinical cure, as defined by a >or=75% reduction in a validated Acute Bronchitis Severity Score by 14 days; analysis was by intention to treat with equivalence defined as

Association between bacterial vaginosis and acute cystitis in women using diaphragms.

We hypothesized that the increased vaginal fluid pH and altered vaginal microflora characteristic of bacterial vaginosis might predispose young women to introital colonization with Escherichia coli and to acute cystitis. To evaluate this hypothesis, we studied 291 women who presented with acute urinary symptoms for association of clinically defined bacterial vaginosis and vaginal conditions associated with this syndrome (increased vaginal fluid pH, absence of lactobacilli, and abnormal vaginal fluid gas-liquid chromatographic patterns) with E coli introital colonization and urinary tract infection. Escherichia coli introital colonization and urinary tract infection were both significantly more frequent among women with a high vaginal fluid pH, an absence of vaginal lactobacilli, or an abnormal vaginal fluid gas-liquid chromatographic pattern characteristic of bacterial vaginosis. Escherichia coli introital colonization was also more frequent in women with bacterial vaginosis. These associations and an association of bacterial vaginosis and E coli urinary tract infection were strong only among the 144 women who were diaphragm users. We conclude that bacterial vaginosis, or an altered vaginal microflora as reflected by an abnormal gas-liquid chromatographic pattern characteristic of bacterial vaginosis, is associated with E coli introital colonization and acute symptomatic urinary tract infection in women who use diaphragms.

Evaluation of chronic urethritis. Defining the role for endoscopic procedures.

We determined the prevalence of structural and functional abnormalities of the lower urinary tract in a carefully defined population of 36 men with chronic urethritis who were attending a sexually transmitted disease clinic. They had experienced symptoms for an average of 12.1 months and had been treated with an average of 5.1 courses of antimicrobial drugs. All had objective evidence of urethral inflammation and negative cultures for both Neisseria gonorrhoeae and Chlamydia trachomatis. Structural abnormalities were documented in nine (25%) of 36 patients but were considered clinically significant in only four. Physical examination and uroflow testing led to clinical suspicion of anatomic abnormalities in all four patients with significant lesions, which included urethral strictures in three patients and benign prostatic hypertrophy in one patient. Additional abnormal findings included wide-bore strictures in three patients and developmental abnormalities of doubtful significance in two patients. Increased numbers of inflammatory cells in expressed prostatic secretions were associated with the presence of structural abnormalities. We conclude that among men with chronic urethritis, careful physical examination and uroflow studies can be used to screen for evidence of structural abnormalities that merit endoscopic evaluation.

Life-threatening interactions between HIV-1 protease inhibitors and the illicit drugs MDMA and gamma-hydroxybutyrate.

Human immunodeficiency virus 1 (HIV-1) protease inhibitors have dramatically reduced the morbidity and mortality due to HIV-1 infection. However, most of these antiretrovirals are also potent inhibitors (and occasionally inducers) of hepatic and intestinal cytochrome P450 systems and, therefore, have the potential to alter the elimination of any substance that utilizes these metabolic pathways. We describe a patient infected with HIV-1 who was treated with ritonavir and saquinavir and then experienced a prolonged effect from a small dose of methylenedioxymetamphetamine (MDMA or ecstacy) and a nearly fatal reaction from a small dose of gamma-hydroxybutyrate (GHB). We also discuss the potential for HIV-1 protease inhibitors to alter the metabolism of other abusable prescribed and illicit substances.

Microbiologic evaluation of cutaneous cellulitis in adults.

Fifty patients with cellulitis were evaluated prospectively using cultures of aspirates from the advancing edge of cellulitis, skin biopsy specimens, and blood. Potential microbial pathogens were isolated in 13 patients. Biopsy specimen cultures were positive in ten patients, while aspirate and blood cultures were positive in five and two, respectively. Aspirate, biopsy, or blood cultures were more often positive in patients with apparent primary lesions than in patients without such lesions. Apparent primary sites of infection were identified and cultured in 24 patients. beta-Hemolytic streptococci were isolated from 17 primary lesions, and coagulase-positive staphylococci were present in 13. Both organisms were isolated from ten primary lesions. Among patients with positive aspirate, biopsy, and/or blood cultures, the same pathogens were also isolated from primary sites in ten of ten patients. Clinical features, including temperature, white blood cell count, and erythrocyte sedimentation rate, were not predictive of positive aspirate, biopsy, or blood cultures. These cultures provided no microbiologic information that was not obtainable from culture of primary lesions.

A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS Clinical Trials Group Protocol 135 Study Team.

OBJECTIVE: To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients. DESIGN: A randomized, open-labeled, comparative trial. SETTING: Outpatient clinics. PATIENTS: Seventy-four patients with HIV and symptomatic bacteremic M. avium infection. INTERVENTIONS: Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. MAIN OUTCOME MEASURE: Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium. RESULTS: No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups. CONCLUSIONS: The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.

A comparison of azithromycin and penicillin V for the treatment of streptococcal pharyngitis.

The safety and efficacy of azithromycin was compared with that of penicillin V in a multicenter study of the treatment of streptococcal pharyngitis in outpatients. Patients were randomized in a 2:1 ratio to either azithromycin 500 mg once on day 1 followed by 250 mg once daily for 4 days, or penicillin V (V-Cillin K) 250 mg every 6 hours for 10 days. Two hundred and forty-two patients from 29 centers were evaluable at the 11th day after enrollment. Five of 229 (2.2%) azithromycin-treated patients were not evaluable because their enrollment isolates of group A beta-hemolytic streptococci (GABHS) were resistant to the drug. In both treatment groups, 99% of patients were clinically cured or improved. Eradication of GABHS occurred in 91% of azithromycin-treated patients compared with 96% of penicillin-treated patients (p = 0.21). Of the patients who had a recurrence of GABHS, clinical evidence of infection occurred in 3 of 13 (23%) patients who had been treated with azithromycin and in 7 of 10 (70%) patients treated with penicillin. Adverse events, generally mild to moderate gastrointestinal complaints, were significantly more common in the azithromycin-treated patients (16.6%) than in penicillin-treated patients (1.7%) (p less than 0.001). Discontinuation because of side effects occurred with similar frequency in both groups. Azithromycin appears to be a safe and effective alternative treatment for streptococcal pharyngitis in adult outpatients.

Progress report on the evaluation of the efficacy of infection surveillance and control programs.

The main objective of the Study on the Efficacy of Nosocomial Infection Control (SENIC Project) is to determine whether infection surveillance and control programs have reduced the rates of nosocomial infection in United States hospitals. To study this question, we stratified all hospitals in the SENIC target population into 16 design strata defined by categories of a surveillance and a control index derived from hospitals' responses to a preliminary screening questionnaire, and estimated the nosocomial infection rates among 339,044 randomly selected patients admitted in 1970 and 1975 through 1976 to 338 hospitals selected randomly from the 16 design strata. Finding that the over-all infection rates, standardized for important confounding variables or covariates, in hospitals with higher intensity programs had increased less from 1970 to 1975-1976 than those of hospitals with low intensity programs would indicate the efficacy of these programs. Potentially important confounding variables and covariates being studied include individual patient risk factors, hospital characteristics and the completeness of hospitals' medical records. Since only the first has been explored sufficiently, no conclusions on efficacy can yet be drawn. The analytic techniques were illustrated with preliminary data on infection rates at the four individual sites of infection.

The joint associations of multiple risk factors with the occurrence of nosocomial infection.

To compare nosocomial infection rates estimated in different time periods or in different hospitals, it is necessary to control for differences in the distribution of factors that substantially influence a patient's susceptibility to infection. To evaluate the associations of multiple risk factors with the occurrence of infection at each of four major sites and to develop composite measures for use in controlling for differences in the distribution of risk among groups of patients, we used a multivariate categorical data analysis technique to study the infection experience of 169,518 patients admitted in 1970 to the 338 hospitals studied in the Study on the Efficacy of Nosocomial Infection Control (SENIC, Project). The relative importance of risk factors and their complex interactions varied by site. The factors found to be highly important for one or more sites were duration of urinary catheterization, the patients' intrinsic risk as reflected in their diagnoses and types of surgical procedures, duration of preoperative hospitalization, duration of operation, anatomic location of surgical procedure, previous infection and steroid or immunosuppressive therapy. Site-specific risk strata and estimates of each patient's probability of acquiring infection were developed from these data for use in future SENIC analyses.

Nosocomial infections in U.S. hospitals, 1975-1976: estimated frequency by selected characteristics of patients.

To obtain estimates of the frequency of nosocomial infections nationwide, those occurring at the four major sites--urinary tract, surgical wound, lower respiratory tract and bloodstream--were diagnosed in a stratified random sample of 169,526 adult, general medical and surgical patients selected from 338 hospitals representative of the "mainstream" of U.S. hospitals. We estimate that in the mid-1970s one or more infections developed in 5.23 percent (+/- 0.16) of the patients and that 6.62 (+/- 0.24) infections occurred among every 100 admissions. Risks were significantly related to age, sex, service, duration of total and of preoperative hospitalization, presence of previous nosocomial or community-acquired infection, types of underlying illnesses and operations, duration of surgery, and treatment with urinary catheters, continuous ventilatory support or immunosuppressive medications. Seventy-one percent of the nosocomial infections occurred in the 42 percent of patients undergoing surgery and 56 percent in the 38 percent financed by Medicare, Medicaid or other public health care plans.

Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium.

OBJECTIVE: To identify the effects of depomedroxyprogesterone acetate (DMPA) on vaginal microbial flora and epithelium. METHODS: Women who desired DMPA for contraception were evaluated before and at 3 and 6 months after initiation of 150-mg DMPA injections every 3 months. At each visit, we assessed genital symptoms, vaginal signs, vaginal microflora, and histopathology by vaginal biopsies. RESULTS: Among 38 women observed for 6 months, there was significant reduction in mean serum estradiol level (99.9 +/- 9.3 pg/mL to 26.6 +/- 1.6 pg/mL, P <.001). The number of subjects with any Lactobacillus did not change, but the number with hydrogen peroxide (H(2)O(2))-positive Lactobacillus decreased from 20% before to 12% after 6 months of DMPA (P =.005). The log concentration in colony-forming units per milliliter of vaginal fluid of H(2)O(2)-positive Lactobacillus decreased in a linear manner from 4. 0 +/- 0.6 at baseline to 2.5 +/- 0.6 after 6 months of DMPA use (P =. 006). The mean number of cell layers in the epithelium was reduced slightly from 28.1 +/- 0.7 to 25.9 +/- 0.9 (P =.05), epithelial thickness decreased from 1.02 +/- 0.04 mm to 0.89 +/- 0.05 mm (P =. 005), and the glycogen-positive thickness decreased from 0.81 +/- 0. 04 mm at baseline to 0.66 +/- 0.05 after 6 months of DMPA use (P =. 005). CONCLUSION: Depomedroxyprogesterone acetate produced a systemic hypoestrogenic state associated with decreased H(2)O(2)-positive Lactobacillus colonization and slight thinning of the glycogen vaginal epithelial layer. Such changes possibly compromise the vaginal barrier to infection.

Sexually transmitted diseases. Urethritis in men.

Gonococcal and nongonococcal urethritis (NGU) are among the most common syndromes afflicting men. NGU is caused primarily by Chlamydia trachomatis and Ureaplasma urealyticum, but the cause is unknown in approximately 20 to 30 percent of cases. Evaluation of a gram-stained urethral smear is generally sufficient to distinguish between gonococcal and nongonococcal urethritis. Owing to the frequent coexistence of Neisseria gonorrhoeae and C. trachomatis in heterosexual men, treatment regimens for gonococcal urethritis should generally include an effective antichlamydial regimen. Complications of urethritis are uncommon, but the causative pathogens produce serious morbidity in women. Prevention of urethritis is based on identification of asymptomatically infected persons who serve as the major reservoir of infection with both N. gonorrhoeae and C. trachomatis.

Diagnosis and treatment of uncomplicated urinary tract infection.

Acute uncomplicated urinary tract infection is one of the most common problems for which young women seek medical attention and accounts for considerable morbidity and health care costs. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials, although resistance is increasing to some of the commonly used agents. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole seem to be more effective than those with beta lactams, regardless of the duration. Because of increasing resistance to trimethoprim-sulfamethoxazole, an alternative regimen such as nitrofurantoin (in a 7-day regimen), a fluoroquinolone, or an oral third-generation cephalosporin may be a better empiric choice in some areas. Acute pyelonephritis caused by highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, but 10- to 14-day regimens are recommended. We prefer to use antimicrobials that attain high renal tissue levels, such as a fluoroquinolone, trimethoprim-sulfamethoxazole, or an aminoglycoside, for pyelonephritis. Acute uncomplicated cystitis or pyelonephritis in healthy adult men is uncommon but is generally caused by the same spectrum of uropathogens with the same antimicrobial susceptibility profile as that seen in women.

Recurrent urinary tract infection in women.

Recurrent urinary tract infections (UTI) are common among young healthy women even though they generally have anatomically and physiologically normal urinary tracts. Women with recurrent UTI have an increased susceptibility to vaginal colonization with uropathogens, which is due to a greater propensity for uropathogenic coliforms to adhere to uroepithelial cells. Risk factors for recurrent UTI include sexual intercourse, use of spermicidal products, having a first UTI at an early age, and having a maternal history of UTIs. Inherited factors may be important in some women with recurrent UTI. Many factors thought to predispose to recurrent UTI in women, such as pre- and post-coital voiding patterns, frequency of urination, wiping patterns, and douching have not been proven to be risk factors for UTI. In contrast to the predominantly behavioral risk factors for young women, mechanical and/or physiological factors that affect bladder emptying are most strongly associated with recurrent UTI in healthy postmenopausal women. The management of recurrent UTI is the same as that for sporadic UTI except that the likelihood of infection with an antibiotic resistant uropathogen is higher in women who have received recent antimicrobials. Strategies to prevent recurrent UTI in young women should include education about the association of recurrent UTI with frequency of sexual intercourse and the usage of spermicide-containing products. Continuous or post-coital prophylaxis with low-dose antimicrobials or intermittent self-treatment with antimicrobials have all been demonstrated to be effective in managing recurrent uncomplicated UTIs in women. Estrogen use is very effective in preventing recurrent UTI in post-menopausal women. Exciting new approaches to prevent recurrent UTI include the use of probiotics and vaccines. Further understanding of the pathogenesis of UTI will lead to more effective and safer methods to prevent these frequent infections.

Practice guidelines for urinary tract infection in the era of managed care.

Acute uncomplicated cystitis among young women is very common, relatively easy to diagnose, and easy to treat with short-course antimicrobial regimens. However, there is great variability among physicians in the approaches to diagnosis and management. Cystitis, therefore, lends itself well to management by clinical practice guidelines which de-emphasize costly office visits, pre-therapy urine cultures and long courses of therapy. As cystitis guidelines continue to be developed by medical care organizations, however, it is important that they be evidence based, include the participation of practicing physicians and provide a mechanism for evaluation to ensure that quality of care and patient satisfaction are not compromised.

The prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in young women.

Four hundred and fifty-two urine isolates from women with acute uncomplicated cystitis and a positive urine culture presenting to a sexually transmitted disease clinic were collected during 1989-1991, and 213 specimens were collected over 1995-1997. The predominant species was Escherichia coli, representing 68% of the isolates; others included Staphylococcus saprophyticus (8%), Group B streptococci (7%), Proteus spp. (6%), Klebsiella spp. (4%) and Enterococcus spp.(3%). More than 10% of the E. coli isolates were resistant to ampicillin, cephalothin, tetracycline and trimethoprim sulfamethoxazole (TMP SMX ) during both study periods, with the greatest increase in resistance to ampicillin and TMP/SMX between the two periods. Six hundred and four urinary tract infection isolates, including 83% E. coli, 7% S. saprophyticus, 3%, Klebsiella spp. 2% Proteus spp., 2% enterococci, 1% Enterobacter spp. and 2% other organisms, were collected from women with acute cystitis attending a university student health service during 1995. Among E. coli isolates, 25% were resistant to ampicillin, 24% to tetracycline and 11%, to TMP SMX. Resistance to fluoroquinolones was essentially absent among gram-negative pathogens. Continued evaluation of susceptibility patterns of pathogens causing acute uncomplicated cystitis to traditional as well as new antimicrobials in well defined populations is necessary to ascertain the optimal empiric therapy.

Urinary tract infection in adults: research priorities and strategies.

Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes, there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies.

Management of acute uncomplicated urinary tract infection in adults.

Acute uncomplicated UTI is one of the most common problems for which young women seek medical attention, and it accounts for considerable morbidity and health care costs. Acute cystitis is a superficial infection of the bladder mucosa, whereas pyelonephritis involves tissue invasion of the upper urinary tract. Localization tests suggest that as many as one third of episodes of acute cystitis are associated with silent upper tract involvement. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials. Because of the superficial nature of cystitis, single-dose and 3-day regimens have gained wide acceptance as the preferred methods of treatment. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole appear to be more effective than those with beta-lactams, regardless of the duration. Acute pyelonephritis does not necessarily imply a complicated infection. Upper tract infection with highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, and 14-day regimens are often used. We prefer to use antimicrobials that attain high renal tissue levels, such as trimethoprim-sulfamethoxazole or quinolones, for pyelonephritis. Women with frequently recurring infections can be successfully managed by continuous prophylaxis, either daily or thrice-weekly, by postcoital prophylaxis, or, in compliant patients, by early self-administration of single-dose or 3-day therapy as soon as typical symptoms are noted. Our drug of choice for all these regimens is trimethoprim-sulfamethoxazole. Acute uncomplicated cystitis in adult men is very uncommon, but it is occasionally noted in homosexual men who practice insertive and intercourse or in heterosexual men whose partners have vaginal colonization with E. coli.

The role of fluoroquinolones in sexually transmitted diseases.

The management of sexually transmitted diseases (STDs) has reached a new level in the era of antibiotic resistance and human immunodeficiency virus infection. To date, no single antimicrobial is capable of eradicating the commonly encountered STD pathogens including Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. Among the marketed fluoroquinolones, ciprofloxacin, ofloxacin, lomefloxacin, and enoxacin all provide excellent in vitro activity (MIC90 < 0.06 micrograms/ml) and excellent in vivo efficacy against N. gonorrhoeae, including multiply resistant isolates (penicillinase-producing N. gonorrhoeae and chromosomally mediated resistant N. gonorrhoeae). Ofloxacin is the only fluoroquinolone approved by the Food and Drug Administration for chlamydial infection. All of the quinolones lack reliable in vitro activity against Ureaplasma urealyticum, a cause of nongonococcal urethritis. Although limited data suggest the usefulness of ciprofloxacin and ofloxacin in the treatment of pelvic inflammatory disease, these drugs cannot currently be recommended for single-agent therapy. Haemophilus ducreyi infections, however, can be managed effectively with the fluoroquinolones. Although their role continues to evolve, this class of drugs cannot be used equally to treat all STDs, and notably, no quinolone to date inhibits T. pallidum.

Nosocomial surgical infections: incidence and cost.

The data reported in this article support the findings of Dr. Altemeier; that is, infections among surgical patients remain a serious problem today. Urinary tract infections account for approximately 40 per cent of nosocomial infections among surgical patients. Surgical wound and skin infections account for one third of the nosocomial infections among surgical patients. Rates for wound infections rise with age, with increased length of hospitalization before surgery, and with increased duration of surgery. They are higher for patients who have an infection at a distant site and for those who have the more hazardous surgical procedures as determined by risk categories. Gram-negative organisms are more prevalent than gram-positive organisms. A nosocomial surgical wound infection lengthens the hospitalization by an average of 7.4 days and raises the cost of hospitalization by more than 800 dollars. Further analysis of the data is necessary in order to identify the risk factors likely to be most helpful in determining which patients are at increased risk of acquiring a nosocomial infection. Only when these factors are identified can the most direct and effective contact and preventive measures be implemented.