Effect of foscarnet cream on experimental UV radiation-induced herpes labialis.

A topical 3% foscarnet cream formulation was evaluated for its ability to treat experimental UV radiation (UVR)-induced herpes labialis in a double-blind study. Healthy adult volunteers with a history of sunlight-induced herpes labialis were randomly assigned at four centers to receive either foscarnet cream (n = 152) or a vehicle control (n = 150). Following measurement of the minimal erythematous dose (MED), the subjects' lips were exposed to 4 MEDs of UV light. Subjects applied the cream on the UVR-exposed area approximately eight times daily beginning immediately after UVR exposure and continuing for 7 days, or until all lesions had a minimum of 4 days of treatment. There were no significant differences between groups in the percentages of subjects that developed any lesion, aborted lesions (did not progress beyond a papule), immediate lesions (developed within 48 h of UVR), or delayed classic lesions (developed 48 h to 7 days after UVR). Treatment with foscarnet significantly reduced the mean lesion area (49 versus 81 mm2; P = 0.01), the maximum lesion area (80 versus 141 mm2; P = 0.01), and the time to healing (P = 0.03) of the delayed classic lesions (n = 78). There was also a trend for a decrease in the mean duration of these lesions (156 versus 191 h; P = 0.08) and the duration of pain (3.9 versus 4.3 days; P = 0.06) in foscarnet-treated subjects. There were no clinically significant adverse reactions. These data suggest that topical foscarnet can be efficacious and deserves further evaluation for the treatment of herpes labialis.

Urinary tract infections.

Management of urinary tract infections may seem quite straightforward, but the patient's age, gender, and other factors can affect management and outcome. Appropriate management can forestall recurring problems and lead to a better quality of life. Dr. Schleupner reviews special situations and outlines treatment options for those cases where individualized care is important.

Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

OBJECTIVE: To determine the effect of acyclovir and prednisone treatment of herpes zoster on chronic pain and quality-of-life outcomes. DESIGN: Randomized, double-blind, placebo-controlled study with a 2 x 2 factorial design. SETTING: 15 university hospitals or affilliated clinics. PATIENTS: 208 immunocompetent patients older than 50 years of age who had localized herpes zoster that developed less than 72 hours before study enrollment. INTERVENTION: Acyclovir or a matched placebo was administered orally, 800 mg five times daily, for 21 days. Prednisone or a matched placebo was administered orally at 60 mg/d for the first 7 days, 30 mg/d for days 8 to 14, and 15 mg/d for days 15 to 21. The four treatments regimens given were acyclovir plus prednisone; acyclovir plus prednisone placebo; prednisone plus acyclovir placebo; and placebos for both acyclovir and prednisone. MEASUREMENTS: Patients were monitored daily for the first 28 days for lesion healing, resolution of pain, return to usual activity, and return to uninterrupted sleep. Monitoring was then done monthly for 6 months. Patients documented analgesic requirements each day, and adverse events and laboratory abnormalities were recorded at each clinical visit. An intention-to-treat analysis was used. RESULTS: Patients were randomly allocated to receive one of the four regimens. Demographic characteristics were similar for each group. Time to total crusting and healing was accelerated for patients receiving acyclovir plus prednisone compared with patients receiving two placebos; the risk ratios were 2.27 (95% Cl, 1.46 to 3.55) for total crusting and 2.07 (Cl, 1.26 to 3.38) for healing. Similarly, compared with the placebo group, patients receiving acyclovir plus prednisone had accelerated time to cessation of acute neuritis (risk ratio, 3.02 [Cl, 1.42 to 6.41]), time to return to uninterrupted sleep (risk ratio, 2.12 [Cl, 1.25 to 3.58]); time to return to usual daily activity (risk ratio, 3.22 [Cl, 1.92 to 5.40]); and time to cessation of analgesic therapy (risk ratio, 3.15 [Cl, 1.69 to 5.89]). In the acyclovir plus prednisone group, resolution of pain during the 6 months after disease onset did not statistically differ from that in the other groups. No important clinical or laboratory adverse events occurred in any group. CONCLUSIONS: In relatively healthy persons older than 50 years of age who have localized herpes zoster, combined acyclovir and prednisone therapy can improve quality of life.

Comparative study of the immunogenicity and safety of Engerix-B administered at 0, 1, 2 and 12 months and Recombivax HB administered at 0, 1, and 6 months in healthy adults.

A randomized trial compared the safety and immunogenicity of Engerix-B (EB) 20 micrograms administered intramuscularly (IM) at 0, 1, 2, and 12 months with Recombivax HB (RHB) 10 micrograms administered IM at 0, 1, and 6 months in healthy adults. At months 3 and 6, significantly more subjects who received EB were seroprotected compared to those who received RHB (84 vs 67%, p = 0.0027; 95 vs 76%, p < 0.001, respectively). SP rates were similar between the vaccination groups approximately 1 year after administration of the initial dose (91 and 83%, respectively; p = 0.1). The vaccines were well tolerated with injection site pain being the most commonly reported adverse event.

Concurrence of Clostridium difficile toxin A enzyme-linked immunosorbent assay, fecal lactoferrin assay, and clinical criteria with C. difficile cytotoxin titer in two patient cohorts.

The accurate and sensitive diagnosis of Clostridium difficile-related diarrhea, normally treated with vancomycin, has become increasingly important in light of the emergence of dangerous new strains of vancomycin-resistant enterococci. In order to improve the threshold for C. difficile diagnosis and treatment, a number of commonly used assays for the diagnosis of C. difficile diarrhea were examined. These included an enzyme-linked immunosorbent assay for C. difficile toxin A (ToxA), a CHO cell culture assay for fecal C. difficile (cyto)toxin B, and a lactoferrin latex agglutination assay for fecal lactoferrin (LFLA). We studied 722 fecal specimens submitted by physicians for C. difficile toxin testing at the Salem, Va., Veterans' Affairs Hospital and at the University of Virginia Medical Center in Charlottesville. Charts were reviewed from 123 Veterans' Hospital patients and 114 University of Virginia patients for clinical criteria indicative of C. difficile diarrhea. An increasing titer of CHO cell cytotoxicity was correlated with an increasing likelihood of ToxA positivity (5 to 90%), LFLA positivity (39 to 77%), and clinical agreement (28 to 85%). However, some data indicate that the CHO cell cytotoxicity assay may be nonspecific when positive only at low titers. When the CHO assay result is positive at high titers, it remains the best diagnostic tool. Yet, when it is positive at a low titer, careful interpretation of the results in conjunction with other assays and the clinical setting is warranted, especially in light of new drug-resistant strains of microorganisms.

A study of the etiologies and treatment of nosocomial pneumonia in a community-based teaching hospital.

OBJECTIVE: To compare the frequency of the pathogens of nosocomial pneumonia in a community-based teaching hospital to the frequencies previously published, and to evaluate recommendations for the therapy of nosocomial pneumonia in this setting. DESIGN: Retrospective review of prospectively acquired data accrued during 9 randomized single-blinded and 4 single-agent investigational antibiotic studies for the therapy of pneumonia in hospitalized patients between 1981 and 1989. SETTING: The study was performed at a university affiliated, community-based teaching Department of Veterans Affairs Medical Center. PATIENTS: Patients were hospitalized on the acute medical/surgical and intermediate medicine wards. Informed consent was obtained prior to enrolling patients into the respective antimicrobial studies. Pneumonia was documented radiographically and clinically for each patient. RESULTS: Two hundred thirty-one episodes of nosocomial pneumonia were treated. Overall, 51% of pneumonias were caused by Streptococcus pneumoniae or Hemophilus influenzae with or without other organisms that were not gram-negative bacilli. Gram-negative bacilli, with or without other organisms, accounted for only 26% of all nosocomial pneumonias. Overall, monotherapy with a cephalosporin (usually a broad-spectrum agent) was equally efficacious compared with combination therapy (87% versus 81%, respectively). Cure rates for nosocomial pneumonias from gram-negative bacilli treated with these 2 therapies also were similar (70% versus 60%, respectively). CONCLUSIONS: In nontertiary care settings, gram-negative bacilli may cause fewer episodes of nosocomial pneumonia (26% in this study) than noted by previously published reports, which indicated that these organisms account for 50% of nosocomial pneumonias. Further, S pneumoniae and H influenzae may account etiologically for many of these nosocomial pneumonias. Monotherapy with an extended-spectrum cephalosporin may be more appropriate than combined treatment with a beta-lactam and an aminoglycoside in a nontertiary care setting, thereby reducing potential toxicity in an older, hospitalized patient population.

Leptospirosis: a forgotten cause of aseptic meningitis and multisystem febrile illness.

Leptospirosis is a worldwide spirochetal zoonosis that spans a clinical spectrum from a mild febrile illness to a severe icteric disease with renal failure (Weil's syndrome). The illness is characteristically biphasic with conjunctival suffusion and an "immune" meningitis during the later phase of illness. Most patients, even those with severe disease, recover without residual organ impairment. The diagnosis is confirmed by serology, by culture of blood or spinal fluid during the first phase of illness, or by culture of urine during the second phase. Doxycycline is the recommended therapy and is effective if given within the first several days of illness; it may also have a role in prophylaxis.

Blinded comparison of cefuroxime to cefaclor for lower respiratory tract infections.

Cefuroxime axetil was compared with cefaclor for the therapy for lower respiratory tract infections. Sixty-one patients were randomized to receive the following drug dosages: (1) cefuroxime axetil, 250 mg orally every 12 hours (21 patients); (2) cefuroxime axetil, 500 mg orally every 12 hours (21 patients); and (3) cefaclor, 500 mg orally every eight hours (19 patients). Of these 61 patients, 80% were male, with a mean age of 59.5 years; 56% had acute pneumonia, and the remainder had an acute bronchitis. Causative pathogens included typical respiratory tract pathogens. Overall, 23 of 27 patients with bronchitis were clinically cured at the end of therapy. Thirty-one of 34 pneumonias were clinically cured or improved at the end of therapy; the three pneumonia treatment failures occurred in the lower dose cefuroxime (n = 2) and cefaclor (n = 1) treatment groups. Overall, bacteriologic cure occurred in 86% of patients treated with 500 mg of cefuroxime axetil compared with 60% of cefaclor-treated patients. Adverse clinical effects were uncommon. From this study, it was concluded that cefuroxime given every 12 hours is at least as clinically efficacious as cefaclor; it is a new oral cephalosporin with pharmacologic and bacterial spectrum advantages over many older agents.

Salmonellosis during infection with human immunodeficiency virus.

Salmonella bacteremia is being identified with increasing frequency in persons infected with the human immunodeficiency virus. Salmonellosis may occur in patients with an established diagnosis of acquired immunodeficiency syndrome (AIDS), or it may be the first manifestation of this disorder. In patients with AIDS, salmonellosis is characterized by recurrent bacteremia despite treatment and a relative paucity of gastrointestinal manifestations. Treatment regimens may be limited by antimicrobial resistance, poor penetration of antibiotics into phagocytes, and drug intolerance; optimal therapy remains to be established. Possible mechanisms to account for this increased frequency and severity of salmonellosis include altered cell-mediated immunity, hemolysis, prior use of antibiotics, and increased exposure to the pathogen. Salmonellae should be considered among the pathogens associated with human immunodeficiency virus infection.

Effect of ketoconazole on the 11-hydroxylation step of adrenal steroidogenesis.

We studied the effect of ketoconazole on glucocorticoid metabolism in three patients before and after a continuous four-hour infusion of ACTH. A single 400 mg oral dose of ketoconazole caused a decrease in serum cortisol concentration, while the concentration of 11-deoxycortisol and its ratio to cortisol increased. The decrease in serum cortisol levels was not accompanied by an increase in plasma ACTH concentration. A four-hour continuous infusion of ACTH resulted in an appropriate elevation of serum cortisol, but with a marked increase in serum concentration of 11-deoxycortisol and its ratio to serum cortisol. We conclude that 400 mg of ketoconazole can decrease cortisol synthesis apparently through a partial block of the 11-beta-hydroxylation step; the observed degree of inhibition may not be sufficient to stimulate the hypothalamic-pituitary-adrenal axis or to cause overt symptoms or signs of adrenal insufficiency; and this partial block of the 11-beta-hydroxylation step becomes more evident during a continuous infusion of ACTH, which can stimulate a normal response of cortisol.

Comparative multicentre evaluation of the safety and efficacy of ceftazidime versus cefamandole for pneumonia.

Ceftazidime and cefamandole were compared in a randomized multicentre trial in hospitalized patients with pneumonia. Of 290 patients enrolled, 92 patients in the ceftazidime group and 71 patients in the cefamandole group were evaluable. Geometric mean MICs of organisms isolated and tested to ceftazidime were within achievable therapeutic serum concentrations of ceftazidime. Satisfactory clinical responses were observed in 91% (84/92) of ceftazidime-treated patients and 83% (59/71) of cefamandole-treated patients (P greater than 0.05). Superinfection occurred in one (1%) ceftazidime-treated patient and in five (7%) cefamandole-treated patients. Side effects were infrequent with either treatment. Ceftazidime is as safe and effective as cefamandole for the treatment of pneumonia due to a variety of Gram-positive and Gram-negative pathogens.

Comparison of ceftazidime with cefamandole for therapy of community-acquired pneumonia.

Ceftazidime and cefamandole were compared in the treatment of pneumonia. The median MIC of ceftazidime for all Streptococcus pneumoniae (n = 17) and Haemophilus influenzae (n = 10) isolates was 0.125 microgram/ml. All other isolates were inhibited by less than 0.5 microgram of ceftazidime per ml, with the exception of a group B streptococcus (MIC = 4 micrograms/ml). Satisfactory clinical responses were observed in 91% (20 of 22) of cefamandole-treated patients and 85% (17 of 20) of ceftazidime-treated patients.

Clinical experience with cefotaxime for the therapy of bacteremias due to gram-positive organisms.

Fifty-five patients with gram-positive bacteremias were treated with cefotaxime after enrollment in comparative and non-comparative study protocols. Forty-nine of these 55 patients were evaluable and followed for their response to therapy and adverse effects. Most patients were white males 50 years of age or older (69%); 45% had two or more serious underlying diseases. Pneumonias caused 59% of these bacteremias, which were etiologically due to Streptococcus pneumoniae (22 episodes), Staphylococcus aureus (15), coagulase-negative staphylococci (3) and other streptococci (12). Overall, 90% of bacteremias were cured with cefotaxime therapy. Among five treatment failures were included three deaths, one due to cefotaxime-associated pseudomembranous colitis, one caused by a bacteremic superinfection due to Pseudomonas aeruginosa and one due to a progressive pneumonia despite therapy. Adverse effects of therapy were infrequent and noteworthy for only one patient with questionable nephrotoxicity and a lack of cefotaxime-associated coagulopathy.

Clinical evaluation of cefotaxime for therapy of lower respiratory tract infections.

A clinical trial was designed to evaluate the efficacy and safety of cefotaxime, a new semisynthetic, broad-spectrum cephalosporin, in the therapy of community-and hospital-acquired pneumonias. Thirty-nine males (mean age, 65 years) were treated for 41 episodes of pneumonia. Only five patient did not have a serious underlying disease; 15 had two or more significant disorders. Sixty-six percent of these pneumonias were due to Streptococcus pneumoniae or Haemophilus influenzae. The minimal inhibitory concentrations for all bacterial isolates ranged from 0.008 to 4 micrograms/ml. Peak serum cefotaxime levels during therapy ranged from 12 to 124 micrograms/ml 1 h after a 1-g dose. Satisfactory bacteriological and clinical responses were observed in 85% of the cases. Four episodes of pulmonary superinfections due to cefotaxime-resistant gram-negative bacilli were noted, each in a patient being mechanically ventilated. Pseudomonas was involved in each of these superinfections, and three were fatal. No serious toxicity or adverse reaction to cefotaxime was seen. The results of this study suggest that cefotaxime is an affective and well-tolerated new cephalosporin antimicrobial agent for the therapy of pneumonia due to susceptible organisms.

Mycobacterium fortuitum as a cause of mastoiditis and wound infection.

Mycobacterium fortuitum is uncommonly pathogenic for man. When implicated, this organism usually infects soft-tissue structures. Therapy necessitates surgical excision and prolonged antimicrobial therapy. A patient had a mastoiditis and wound infection due to this organism. Her successful treatment included radical debridement and prolonged therapy with several antimicrobials. The necessity for including mycobacteria in the differential diagnosis of ear, nose, and throat diseases is emphasized by our experience. The complexities of management of these infections are reviewed.

Peritoneal fluid concentrations of gentamicin in patients with spontaneous bacterial peritonitis.

Simultaneous peritoneal fluid and serum gentamicin assays were performed at 1- or 4-h intervals after the intravenous administration of gentamicin (3 to 5 mg/kg per day) during nine episodes of spontaneous bacterial peritonitis in cirrhotic patients. Mean peritoneal fluid levels were 4.2 micrograms/ml, whereas simultaneous mean serum levels were 6.1 micrograms/ml (mean percent diffusion into ascites of 67.8%). Three additional patients with uninflamed ascites demonstrated lower levels of diffusion. Regression analysis revealed a positive correlation between simultaneous serum and peritoneal fluid levels. We conclude that diffusion of gentamicin from serum into peritoneal fluid during spontaneous peritonitis is therapeutically adequate if sufficient serum levels are maintained.

A pseudoepidemic of pulmonary fungal infections related to fiberoptic bronchoscopy.

During a three-week period a pseudoepidemic of fungal infections occurred involving patients from two different services. Trichosporon cutaneum and a Penicillium species were isolated from bronchial washings and sputa obtained after fiberoptic bronchoscopy on eight clinically uninfected patients. Investigation revealed contamination of cocaine solutions used for topical anesthesia during bronchoscopy. Contamination is thought to have occurred during preparation of the solutions by pharmacy personnel. Revision of techniques used in formulating and dispensing the solutions resulted in cessation of the pseudoepidemic.