Hemorrhagic adenovirus cystitis after renal transplantation.

PURPOSE: Viral infections are a major cause of postoperative morbidity and mortality after renal transplantation. Although cytomegalovirus, Epstein-Barr virus, and polyoma virus infections are common, there have been only a few reports of adenovirus infections. MATERIALS AND METHODS: We report an unusual case of a patient with adenovirus-induced hemorrhagic cystitis (AHC). We also performed a comprehensive MEDLINE review to identify similar cases. We then compared the presentation, management, and outcome of all patients to identify patterns that may facilitate the diagnosis and management of AHC. RESULTS: Review of the literature revealed 36 other reported cases of AHC in renal transplant recipients. Thirty-six of the 37 cases occurred within 1 year of transplantation. These patients presented with fever, dysuria, hematuria, and graft dysfunction. Thirty-four received high-dose steroids for treatment of symptoms of acute rejection. Four patients received antiviral medications. The infection was self-limited with mean duration of symptoms being 20 days. In all cases, serum creatinine returned to baseline or near baseline levels with resolution of symptoms. CONCLUSIONS: Although uncommon, AHC usually presents within 1 year of renal transplantation with a consistent constellation of symptoms. The infection appears to be self-limited with full recovery in most patients within 4 weeks. The efficacy of antiviral medications could not be determined in this review.

Early discharge of infected patients through appropriate antibiotic use.

BACKGROUND: Patients with infections are usually discharged from the hospital with antibiotics when afebrile and clinically improved. OBJECTIVES: To compare outcomes of early vs conventionally discharged patients and to examine the role of antibiotic use in the discharge process. METHODS: One hundred eleven patients hospitalized with cellulitis, community-acquired pneumonia, or pyelonephritis (urinary tract infection) discharged from the hospital early in their clinical course before defervescence by an infectious diseases hospitalist (L.J.E.) were compared in a case-controlled study with 112 patients discharged from the hospital according to conventional standards of care by internal medicine (IM) hospitalists. Patients were matched for age, sex, diagnosis, and comorbidities. Outcomes were determined for average lengths of stay, readmission to the hospital within 30 days with the same diagnosis, satisfaction with their discharge program, and time to return to their normal activities of daily living. RESULTS: Patients cared for by the infectious diseases hospitalist had a shorter average length of stay (mean difference, 1.7 days), no readmissions, higher satisfaction scores, and a shorter time to return to their activities of daily living, compared with those cared for by the IM hospitalists. Analysis of the antibiotics that patients were discharged with revealed that the infectious diseases hospitalist used outpatient parenteral antibiotic therapy more frequently than IM hospitalists in the treatment of cellulitis, and switched from intravenous to oral antibiotics sooner than IM hospitalists for patients with community-acquired pneumonia and urinary tract infection. CONCLUSIONS: The infectious diseases hospitalist discharged patients from the hospital earlier than the IM hospitalists by more efficient use of antibiotics. The earlier discharge did not adversely affect outcomes.

Targeting lurking pathogens in acute traumatic and chronic wounds.

The appropriate antimicrobial treatment for skin and soft tissue following acute trauma is determined by the mechanism of injury, time from injury to treatment, environmental wound contamination, pathogenicity of colonizing bacteria, and patient-specific issues. These factors can be used to predict the risk of secondary infection of wounds. Although common skin pathogens (such as Staphylococcus aureus and group A Streptococcus) cause most secondary wound infections, antibiotic therapy sometimes must be directed against unusual pathogens that are associated with atypical wounds, such as animal bites (amoxicillin with clavulanate for Pasteurella multocida) and plantar puncture wounds (ciprofloxacin for Pseudomonas aeruginosa). This customized treatment approach is also appropriate for chronic wounds, such as pressure and diabetic foot ulcers. In addition to antibiotic therapy, wound management may include surgical debridement. Active areas of investigation in wound management include the use of growth factors and hyperbaric oxygen.

Mupirocin cream is as effective as oral cephalexin in the treatment of secondarily infected wounds.

BACKGROUND: Topical antimicrobials have been considered for treatment of secondarily infected wounds because of the potential for reduced risk of adverse effects and greater patient convenience. We compared mupirocin cream with oral cephalexin in the treatment of wounds such as small lacerations, abrasions, or sutured wounds. METHODS: In 2 identical randomized double-blind studies, 706 patients with secondarily infected wounds (small lacerations, abrasions, or sutured wounds) received either mupirocin cream topically 3 times daily or cephalexin orally 4 times daily for 10 days. RESULTS: Clinical success at follow-up was equivalent in the two groups: 95.1% and 95.3% in the mupirocin cream and the cephalexin groups, respectively (95% confidence interval [CI], -4.0% to 3.6%; P = .89). The intention-to-treat success rate was 83% in both groups. Bacteriologic success at follow-up was also comparable: 96.9% in the mupirocin cream and 98.9% in the cephalexin groups (95% CI, -6.0% to 2.0%; P = .22). The occurrence of adverse experiences related to study treatment was similar for the 2 groups, with fewer patients in the mupirocin cream group reporting diarrhea (1.1% vs 2.3% for cephalexin). CONCLUSIONS: Mupirocin cream applied topically 3 times daily is as effective as oral cephalexin given 4 times daily for the treatment of secondarily infected wounds and was well tolerated.

Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS.

BACKGROUND: Disseminated Mycobacterium avium complex infection eventually develops in most patients with the acquired immunodeficiency syndrome (AIDS). This infection results in substantial morbidity and reduces survival by about six months. METHODS: We conducted two randomized, double-blind, multicenter trials of daily prophylactic treatment with either rifabutin (300 mg) or placebo. All the patients had AIDS and CD4 cell counts < or = 200 per cubic millimeter. The primary end point was M. avium complex bacteremia as assessed monthly by blood culture. The secondary end points were signs and symptoms associated with disseminated M. avium complex infection, adverse events, hospitalization, and survival. RESULTS: In the first trial, M. avium complex bacteremia developed in 51 of 298 patients (17 percent) assigned to placebo and 24 of 292 patients (8 percent) assigned to rifabutin (P < 0.001). In the second trial, bacteremia developed in 51 of 282 patients in the placebo group (18 percent) and 24 of 274 patients in the rifabutin group (9 percent) (P = 0.002). Rifabutin significantly delayed fatigue, fever, decline in the Karnofsky performance score (by > or = 20 percent), decline in the hemoglobin level (by more than 10 percent), elevation in alkaline phosphatase, and hospitalization. The incidence of adverse events was similar with rifabutin and placebo. Overall survival did not differ significantly between the two groups, although there were fewer deaths with rifabutin (33) than with placebo (47) during the double-blind phase (P = 0.086). The distribution of minimal inhibitory concentrations of rifabutin among the isolates of M. avium complex did not differ significantly between the treatment groups. CONCLUSIONS: Rifabutin, given prophylactically, reduces the frequency of disseminated M. avium complex infection in patients with AIDS and CD4 counts < or = 200 per cubic millimeter.

Long-term suppression of recurrent genital herpes with acyclovir. A 5-year benchmark. Acyclovir Study Group.

BACKGROUND AND DESIGN: This multicenter trial (19 sites) was initiated in 1984 in more than 1100 immunocompetent individuals with a history of frequently recurring genital herpes (mean, > or = 12 episodes per year). The first year of this suppressive therapy trial was placebo controlled, with acyclovir being provided for episodic treatment in both groups. Thereafter, patients were treated with open-label acyclovir suppressive therapy on a long-term basis (400 mg twice daily) to continue to assess its long-term safety and efficacy. Complete data are available on 389 of the 430 patients who began the fifth year of the study. RESULTS: Patients were seen quarterly for review of diaries and clinical laboratory evaluations. The percentage of patients recurrence free for any 3-month quarter of the fifth year ranged from 86% to 90%. The mean annual number of recurrences per patient declined from 1.7 during the first year to 0.8 during the fifth year of suppressive therapy. The frequency of false prodromes has also decreased over time. More than 20% of the patients receiving suppressive therapy for 5 years have been recurrence free the entire time. The duration of herpetic outbreaks during suppressive therapy has not changed. CONCLUSION: This study extends the safety and efficacy profile of oral acyclovir in the suppression of genital herpes to 5 years. The majority of the patients were recurrence free on an annual basis during suppressive therapy. Therapy was well tolerated. Acyclovir usage was not associated with serious side effects or cumulative toxicity.

Recurrence of condylomata acuminata following cryotherapy is not prevented by systemically administered interferon.

OBJECTIVE: To determine whether interferon alpha-2a, when utilised as adjuvant chemotherapy following ablation of condylomata acuminata (genital warts) by cryotherapy, is effective in the prevention of recurrences. DESIGN: Randomised, placebo-controlled, double-blind study. Statistical analysis was by 2-tailed Fisher's Exact Test. PATIENTS: 97 patients with recurrent condylomata acuminata. INTERVENTION: 49 patients were treated with cryotherapy plus subcutaneously administered interferon alpha-2a, and 48 received cryotherapy plus placebo. Of these, 36 and 37 patients, respectively, completed the study and were evaluable. MAIN OUTCOME MEASURE: Clinical eradication of condylomata for six months following adjuvant chemotherapy. RESULTS: By completion of the adjuvant chemotherapy, 10 (28%) interferon recipients and 16 (43%) placebo recipients experienced recurrences. At six months follow-up, 25 (69%) interferon and 27 (73%) placebo recipients experienced recurrences. In the six months following interferon therapy, only 31% of interferon and 27% of placebo recipients remained free of recurrences (p = 0.99). CONCLUSIONS: Interferon alpha-2a administered subcutaneously offers no benefit as a chemotherapeutic adjuvant to cryotherapy when used alone in the therapy of genital warts in this population of patients with recurrent condylomata.

Continuous five-year treatment of patients with frequently recurring genital herpes simplex virus infection with acyclovir.

This study presents data relative to the efficacy and safety following the continuous use of oral acyclovir in the treatment of genital herpes over a 5-year period. In this study, 1,146 patients (53% males; 47% females) were originally enrolled. These included patients with a history of frequently recurring genital herpes (mean > 12 episodes per year). During the first year, patients were randomized between those receiving 400 mg of acyclovir twice daily and an equal number receiving placebo. Additionally, acyclovir was utilized for episodic treatment (ES) in both groups. Thereafter, patients received open-label acyclovir suppressive therapy for the remainder of the study period. Complete data are available on 389 patients who completed the fifth year of therapy. All the participants who completed the fifty year of the study had completed either 4 or 5 years of daily suppressive acyclovir therapy. During the first year, a significant decrease in the frequency of recurrences in patients receiving continuous acyclovir (SS) was noted as compared to the placebo group (1.7 vs. 12.5 recurrences; P < 0.0001). From year one to the end of year three, a progressive decrease in the frequency of recurrences was noted in both groups. Yet, those patients who had received SS for the full 3 years had significantly fewer recurrences than those who had received ES in the first year (P = 0.05). During years four and five, the decrease in frequency of recurrences between the ES and SS groups was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials.

OBJECTIVE: To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. DESIGN: Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. SETTING: Multiple centers in the United States. PATIENTS: Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. INTERVENTION: Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. MEASUREMENTS: Changes in mean hematocrit, transfusion requirement, and quality of life. RESULTS: Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. CONCLUSION: Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.

Oral ofloxacin for infections caused by bacteria resistant to oral antimicrobial agents.

We conducted an open trial of oral ofloxacin, 400 mg q 12 hr, in the treatment of infections caused by Pseudomonas aeruginosa and other bacteria resistant to traditional oral antibiotics. There were 53 evaluable subjects, 30 having infection of the skin/skin structure, 13 of the respiratory tract, six of bone, and four complicated infections of the genitourinary tract. Most subjects (72%) had previously failed a course of antibiotic therapy for their infections. Ofloxacin therapy was administered an average of 45 days per patient, and was well tolerated. Clinical success was observed in 40 (74%) subjects, with failure in 13 (26%). Responses ranged from 50% success for six lower respiratory tract infections to 100% success for six cases of osteomyelitis. There were 28 P. aeruginosa with 22 Gram-positive and 24 other Gram-negative infections. Of 28 cases in which P. aeruginosa was implicated as a pathogen, 19 (68%) were successfully treated with ofloxacin therapy. Overall, 63 (85%) of 74 pathogens were eradicated. Of the 11 persistent organisms, five were P. aeruginosa in which resistance to ofloxacin emerged during therapy. Our data imply ofloxacin to be effective for infections due to ofloxacin-susceptible organisms other than P. aeruginosa; for this pathogen, ofloxacin therapy is associated with a high degree of failure. If ofloxacin is used for infection due to P. aeruginosa, microbiologic surveillance is necessary for cases that either fail to respond or relapse clinically.

Parenteral antibiotic therapy in outpatients: quality assurance and other issues in a protohospital.

Antibiotics can be administered parenterally to outpatients in order to achieve adequate serum levels to treat such infections as endocarditis, osteomyelitis and diabetic foot infections, and to eradicate such difficult-to-treat organisms as methicillin-resistant Staphylococcus aureus, cephalothin-resistant gram-negative bacilli and invasive fungal infections. At Intracare, a free-standing clinic for such therapy, 3,247 outpatients have been treated to date. Besides the type of infection, criteria for patient selection include improvement in the patient's condition, a desire to leave the hospital, an adequate support structure at home, patient compliance and adequate insurance coverage. The most frequently treated infections have been osteomyelitis, followed by infection of skin and skin structure. Ceftriaxone and cefazolin are the two most frequently utilized antibiotics. The program at Intracare is used to examine such issues of quality assurance as patient compliance, therapeutic outcome, adverse events and patient satisfaction in this largely unregulated multibillion dollar industry. It is likely that such infusion centers will evolve into protohospitals, day care centers for present-day medical-surgical patients not occupying intensive care beds.

Multicenter study of a single 500-mg dose of cefotaxime for treatment of uncomplicated gonorrhea.

One hundred thirty-seven evaluable patients with uncomplicated gonorrhea were treated with a single 500-mg intramuscular dose of cefotaxime. All isolates were susceptible to concentrations of cefotaxime less than or equal to 0.1 microgram/ml. The minimum concentration of cefotaxime needed to inhibit 90% of isolates was less than 0.04 microgram/ml. At follow-up, infection was eradicated in 181 of 187 (97%) infection sites. Bacteriologic cures of 100 of 101 (99%), 55 of 56 (98%), 23 of 25 (92%), and 3 of 5 (60%) were attained at the urethral, endocervical, rectal, and oropharyngeal sites, respectively. Side effects were minor, and 90% of patients rated the injection-site pain as absent or mild. A single 500-mg dose of cefotaxime is an effective, economic treatment for uncomplicated gonorrhea.

A randomized trial of combination therapy with intralesional interferon alpha 2b and podophyllin versus podophyllin alone for the therapy of anogenital warts.

To determine the value of combining interferon with standard local therapy in the treatment of human papillomavirus infection, 97 patients with anogenital warts were randomized to a short course of either interferon plus podophyllin or podophyllin alone. Interferon alpha 2b (1.5 x 10(6) IU) was injected intralesionally and podophyllin resin applied topically to each of three warts once weekly for 3 weeks. Maximal responses occurred within 2 weeks of therapy, and overall there was complete clearance of treated warts in 67% of interferon and podophyllin versus 42% of podophyllin recipients (P less than .05, chi 2). Clearance rates were greater in women, patients with warts of less than or equal to 12 months' duration, and HIV-seronegative patients. Of patients with complete clearance, 67% of interferon and podophyllin and 65% of podophyllin recipients experienced recurrences. Thus, in short treatment courses of anogenital warts, intralesional interferon enhanced the effect of topical podophyllin, and trials of combination therapy using more intensive or prolonged regimens of interferon are warranted.

Characterization of clones of HIV-1 infected HuT 78 cells defective in gag gene processing and of SIV clones producing large amounts of envelope glycoprotein.

Single-cell clones of HIV-1 (FRE-3) or SIV/Mne infected HuT 78 cells were obtained by plating dilutions of virally infected HuT 78 cells on a monolayer of sheep choroid plexus cells in 96-well microtiter plates. Several of these clones produce HIV-1 virus mutants that accumulate the gag precursor polyprotein and lack a functional protease. These protease-deficient viruses are non-infectious and consist of aberrant "immature" virus particles as determined by electron microscopy. Several SIV mutants are also described that produce large amounts of either the envelope glycoprotein gp120 or the nucleic acid binding gag protein. These mutants are useful for the purification of these retroviral proteins, in developing assays of protease inhibitors, and in preparing SIV envelope protein vaccines.

A trial using early preoperative administration of cefonicid for antimicrobial prophylaxis with hysterectomies.

A single dose of cefonicid given 3.5-5.0 hours or 0.5-1.0 hour preoperatively was compared with cefoxitin given as five doses beginning 0.5-1.0 hour preoperatively for prophylaxis of infection in 202 patients undergoing vaginal or abdominal hysterectomy. The administration of cefonicid 3.5-5.0 hours preoperatively was intended to simulate situations where surgery may be delayed or prolonged. The trial was double-blind, and patients were randomized to one of the three regimens. Operative site infections were noted in 6.2 percent of patients (7/113) who received cefonicid 3.5-5.0 hours preoperatively, in 7.0 percent of patients (3/43) who received cefonicid 0.5-1.0 hour preoperatively, and in 4.3 percent of patients (2/46) who received cefoxitin (p greater than 0.05). Enterococci were isolated most frequently from operative-site infections. When administered 3.5-5.0 hours preoperatively, cefonicid was as effective as more traditional regimens.