Antiretroviral nonadherence and condomless sex in the HIV Outpatient Study, USA, 2007-2014.

Effective antiretroviral therapy (ART) reduces plasma HIV RNA viral load (VL) to undetectable levels and its effectiveness depends on consistent adherence. Consistent adherence and use of safe sex practices may substantially decrease the risk of HIV transmission. We sought to explore the potential association between self-reported nonadherence to ART and engaging in unsafe sexual practices capable of transmitting HIV. Using clinical and audio computer-assisted self-interview data from the prospective HIV Outpatient Study from 2007 to 2014, we assessed the frequency of self-reported ART nonadherence during the three days prior to the survey among HIV-infected persons in care and factors associated with self-reported ART nonadherence. Of 1729 patients included in this analysis (median age = 48 years, 74.3% men who have sex with men), 17% were nonadherent, 15% had a detectable VL, and 42% reported condomless anal or vaginal sex in the past six months. In multivariable analysis, self-reported nonadherence was independently associated with younger age (adjusted odds ratio [aOR] 0.8 per additional ten years, [95% CI] 0.7-1.0), non-Hispanic black race/ethnicity (aOR 1.9; 95% CI 1.4-2.6 versus white), public health insurance (aOR 1.6, 95% CI 1.2-2.3 compared with private), survey date in 2011-2014 versus 2007-2010 (aOR 0.7, 95% CI 0.5-0.9), CD4 cell count ≥ 500 versus < 200 cells/mm3 (aOR 0.3, 95% CI 0.2-0.5), greater number of ART regimen doses (aOR 1.6, 95% CI 1.3-2.2), and binge drinking (aOR 1.4, 95% CI, 1.1-1.9). In this analysis, self-reported nonadherence was not associated with engaging in condomless sex.

CD4 cell count at initiation of ART, long-term likelihood of achieving CD4 >750 cells/mm3 and mortality risk.

OBJECTIVES: We sought to evaluate associations between CD4 at ART initiation (AI), achieving CD4 >750 cells/mm(3) (CD4 >750), long-term immunological recovery and survival. METHODS: This was a prospective observational cohort study. We analysed data from ART-naive patients seen in 1996-2012 and followed ≥3 years after AI. We used Kaplan-Meier (KM) methods and log-rank tests to compare time to achieving CD4 >750 by CD4 at AI (CD4-AI); and Cox regression models and generalized estimating equations to identify factors associated with achieving CD4 >750 and mortality risk. RESULTS: Of 1327 patients, followed for a median of 7.9 years, >85% received ART for ≥75% of follow-up time; 64 died. KM estimates evaluating likelihood of CD4 >750 during 5 years of follow-up, stratified by CD4-AI <50, 50-199, 200-349, 350-499 and 500-750, were 20%, 25%, 56%, 80% and 87%, respectively (log-rank P < 0.001). In adjusted models, CD4-AI ≥200 (versus CD4-AI <200) was associated with achievement of CD4 >750 [adjusted HR (aHR) = 4.77]. Blacks were less likely than whites to achieve CD4 >750 (33% versus 49%, aHR = 0.77). Mortality rates decreased with increasing CD4-AI (P = 0.004 across CD4 strata for AIDS causes and P = 0.009 for non-AIDS death causes). Among decedents with CD4-AI ≥50, 56% of deaths were due to non-AIDS causes. CONCLUSIONS: Higher CD4-AI resulted in greater long-term CD4 gains, likelihood of achieving CD4 >750, longer survival and decreased mortality regardless of cause. Over 80% of persons with CD4-AI ≥350 achieved CD4 >750 by 4 years while 75% of persons with CD4-AI <200 did not. These data confirm the hazards of delayed AI and support early AI.

A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I).

BACKGROUND: No clinical trial results directly comparing two nucleoside analog pairs in a drug regimen for HIV that includes a protease inhibitor are available. OBJECTIVE: To compare the safety and efficacy of stavudine (d4T) + lamivudine (3TC) with zidovudine (ZDV) + 3TC, each in combination with indinavir (IDV). DESIGN: Randomized, open-label, multi-center. SETTING: Fifteen HIV clinical research centers. PATIENTS: Two-hundred and four antiretroviral-naive HIV-1-infected-patients with CD4 cell counts > or = 200 x 10(6)/l and HIV-1 RNA > or = 10,000 copies/ml (bDNA assay), modified to 5000 copies/ml. INTERVENTION: d4T 40 mg twice a day, 3TC 150 mg twice a day plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h (modified to 300 mg every 12 h) plus 3TC and IDV. MEASUREMENTS: Primary endpoint: plasma HIV-1 RNA < 500 copies/ml. Additional endpoints: HIV-1 RNA < or = 50 copies/ml; change from baseline in HIV-1 RNA and CD4 cell counts; safety and adverse events. RESULTS: For HIV-1 RNA, 62% of patients on d4T + 3TC + IDV and 54% of patients on ZDV + 3TC + IDV had < 500 copies/ml HIV RNA at weeks 40 through 48 [90% confidence interval, -0.204 to 0.036; P= 0.213], with 49% and 47% respectively achieving < or = 50 copies/ml at 48 weeks (90% CI, -0.134 to 0.096; P = 0.834). Median change in CD4 cell counts at 48 weeks was +227 x 10(6)/l and +198 x 10(6)/l for the d4T- and ZDV-containing arms, respectively. The median time-weighted average change from baseline in CD4 cell counts was significantly greater at 48 weeks in the d4T-containing arm (142 x 10(6)/l versus 110 x 10(6)/l; P = 0.033). Serious adverse events were not significantly different between treatment arms, but there were significant differences for frequency of adverse events of all severity with increased nausea and vomiting in the ZDV-containing arm, and increased diarrhea and rash in the d4T-containing arm. CONCLUSIONS: These results support the choice of d4T + 3TC as a nucleoside analog pair in combination with a protease inhibitor in an initial HIV treatment regimen.

Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

Discontinuation of chemoprophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection. HIV Outpatient Study (HOPS) Investigators.

BACKGROUND: HIV-infected patients with sustained immunologic improvement from antiretroviral therapy may be able to discontinue chemoprophylaxis against Pneumocystis carinii pneumonia (PCP). OBJECTIVE: To compare PCP incidence in HIV-infected patients who had sustained CD4+ lymphocyte counts greater than 200 cells/mm3 and who either discontinued or continued PCP prophylaxis. DESIGN: Nonrandomized prospective cohort study. SETTING: 10 HIV clinics in eight U.S. cities. PATIENTS: 146 patients had follow-up visits for a mean of 18.2 months after discontinuation of PCP prophylaxis, and 345 patients who continued PCP prophylaxis had follow-up visits for a mean of 14.0 months. MEASUREMENTS: Incidence of PCP. RESULTS: Patients who discontinued PCP prophylaxis had higher maximum and minimum CD4+ cell counts and lower vira loads than patients who continued PCP prophylaxis. Pneumocystis carinii pneumonia did not develop in either group (upper 95% exact binomial confidence limit of incidence for those who discontinued PCP prophylaxis, 2.3/100 person-years). CONCLUSIONS: Discontinuation of PCP chemoprophylaxis may be appropriate for some HIV-infected ambulatory patients.

Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV outpatient study (HOPS).

PURPOSE: Most HIV-infected persons are now treated as ambulatory patients. Obtaining continually updated data about these patients' changing conditions, therapies, and reimbursement is essential to health care provision and planning. The systematic tracking of patient medical and laboratory information in an ongoing commercial data collection program (The Health Research Network) allows clinicians to better understand health outcomes, practice patterns, and epidemiologic trends for their patients. METHODS: To evaluate trends in conditions and therapies of ambulatory HIV-infected patients, we analyzed such data electronically and prospectively collected in the HIV Outpatient Study (HOPS) from 1992 through 1996 from 1876 patients seen in 11,755 clinic visits to ten HIV clinical practices. RESULTS: Patients were as likely to be diagnosed with Mycobacterium avium complex ([MAC] 5.4 cases per 100 person-years) or wasting syndrome (7.8 cases per 100 person-years), as Pneumocystis carinii pneumonia ([PCP]; 7.6 cases per 100 person-years) or Kaposi sarcoma ([KS]; 6.9 cases per 100 person-years). A nested analysis showed that HIV-infected cigarette smokers were at substantially greater risk of pneumonia (relative hazard [RH] = 2.3), bronchitis (RH = 1.7) and hairy leukoplakia (RH = 1.9) than nonsmokers. By 1996, 35 (56%) of 62 patients with PCP, 9 (30%) of 30 patients with other pneumonias, 28 (90%) of 31 patients with KS, 35 (73%) of 48 patients with MAC, and 24 (63%) of 38 patients with cytomegalovirus retinitis were treated without hospitalization. CONCLUSIONS: The HOPS provides continually updated information on the changing characteristics, conditions, and therapy of ambulatory HIV-infected patients.

The use of a transscrotal testosterone delivery system in the treatment of patients with weight loss related to human immunodeficiency virus infection.

PURPOSE: Weight loss is a strong predictor of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. Men with acquired immunodeficiency syndrome (AIDS) lose body cell mass. Hypogonadism is also common. This study tested the efficacy of a testosterone transscrotal patch (6 mg/day) in improving body cell mass and treating hypogonadism in these patients. SUBJECTS AND METHODS: This multicenter, randomized, double-blinded, placebo-controlled trial was conducted from August 1995 to October 1996 in 133 men, 18 years of age and older, who had AIDS, 5% to 20% weight loss, and either a low morning serum total testosterone level (<400 ng/dL) or a low free testosterone level (<16 pg/mL). Outcomes included weight, body cell mass as measured using bioelectrical impedance analysis, quality of life, and morning measurements of serum testosterone and dihydrotestosterone levels, lymphocyte subsets, and HIV quantification. RESULTS: There were no significant differences in baseline weight, CD4 cell counts, or HIV serum viral quantification between treatment arms. Morning total and free testosterone levels increased in those treated with testosterone, but not with placebo. Following 12 weeks of treatment there were no differences (testosterone-placebo) in mean weight change (-0.3 kg [95% confidence interval (CI): -1.4 to 0.8]) or body cell mass (-0.2 kg [95% CI: -1.0 to 0.6]) in the two groups. There were also no changes in quality of life in either group. CONCLUSION: Hypogonadal men with AIDS and weight loss can achieve adequate morning serum sex hormone levels using a transscrotal testosterone patch. However, this system of replacement does not improve weight, body cell mass, or quality of life.

Rapidly progressive herpetic retinal necrosis: a blinding disease characteristic of advanced AIDS.

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.

Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia.

We studied the effects of long-term (12 months) dronabinol in 94 late-stage acquired immunodeficiency syndrome (AIDS) patients (mean CD4 count of 45/mm3) who previously participated in a 6-week study (placebo versus dronabinol). All patients received dronabinol orally-2.5 mg twice daily (90%) or 2.5 mg once daily (10%). Appetite was measured using a visual analogue scale for hunger (VASH). Dronabinol was associated with consistent improvement in mean appetite. Patients previously treated with dronabinol continued to show improvement in VASH (percent change from baseline of 6-week trial: 48.6-76.1% at each month), whereas those previously treated with placebo exhibited substantial improvement in mean appetite, particularly during the initial 4 months of treatment (48.5-69.9%). Thereafter, dronabinol was associated with a VASH change at least twice baseline. Patients tended toward stable body weight for at least 7 months. Adverse events were primarily related to known central nervous system effects of dronabinol. These data support long-term, safe use of dronabinol for anorexia associated with weight loss in patients with AIDS.

Randomised trial of MNrgp120 HIV-1 vaccine in symptomless HIV-1 infection.

BACKGROUND: Most individuals infected with HIV-1 show disease progression despite both cellular and humoral immune responses. We investigated whether immunisation of patients who had symptomless HIV-1 infection with an envelope subcomponent vaccine (MNrgp120) to augment immune response can slow progression of HIV-1 disease. METHODS: In a randomised, double-blind, placebo-controlled trial, carried out in university infectious disease clinics and community infectious disease practices, we enrolled 573 HIV-infected patients with CD4 counts above 600 cells/microL (0.6 x 10(9)/L). Patients received 600 micrograms vaccine or placebo by intramuscular injection monthly for 6 months then every alternate month throughout the study. The primary endpoint was the rate of decline in CD4 count; secondary endpoints were HIV-1 RNA concentrations in plasma and minor clinical events associated with HIV. Analysis was by intention to treat. FINDINGS: At baseline, the study participants had a mean CD4 count of 775 cells/microL (SD 172) and 89% of participants had detectable HIV RNA (> 200 copies/mL). These RNA-positive individuals had a median viral load of 9250 copies/mL (IQR 2670-26960). Analysis after 15 months of follow-up of the 568 subjects who had at least one CD4 count done after randomisation showed no difference between the 287 vaccine recipients and 281 placebo recipients in rate of decline of CD4 count (yearly decrease 53.8 [SE 7.6] vs 42.3 [7.6] cells/microL; ratio of mean gradients 1.27 [95% CI 0.63-2.55]) or in plasma HIV-1 RNA concentrations (p > or = 0.63). The study was designed with power to detect a vaccine-induced reduction in rate of decline in CD4 count of 60%; these results exclude with 95% confidence a reduction of 40% or more. More vaccine-treated patients than placebo recipients showed a 50% decrease in CD4 count (11 vs 5; relative risk 2.15 [95% CI 0.76-6.12], p = 0.13). The frequencies of HIV-related minor clinical events were similar in the two groups. Pain at the injection site was the only adverse event that occurred more frequently in vaccine-treated group. INTERPRETATION: Postinfection immunisation of symptom-free HIV-infected patients with MNrgp120 vaccine did not alter HIV-1 disease progression as measured by immunological, virological, and clinical endpoints over a 15-month period.

A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome.

BACKGROUND: Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic. METHODS: We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months. RESULTS: After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively). CONCLUSIONS: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.

Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.

The effects of dronabinol on appetite and weight were evaluated in 139 patients with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional study. Patients were randomized to receive 2.5 mg dronabinol twice daily or placebo. Patients rated appetite, mood, and nausea by using a 100-mm visual analogue scale 3 days weekly. Efficacy was evaluable in 88 patients. Dronabinol was associated with increased appetite above baseline (38% vs 8% for placebo, P = 0.015), improvement in mood (10% vs -2%, P = 0.06), and decreased nausea (20% vs 7%; P = 0.05). Weight was stable in dronabinol patients, while placebo recipients had a mean loss of 0.4 kg (P = 0.14). Of the dronabinol patients, 22% gained > or = 2 kg, compared with 10.5% of placebo recipients (P = 0.11). Side effects were mostly mild to moderate in severity (euphoria, dizziness, thinking abnormalities); there was no difference in discontinued therapy between dronabinol (8.3%) and placebo (4.5%) recipients. Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS.

The individual microbiologic effect of three antimycobacterial agents, clofazimine, ethambutol, and rifampin, on Mycobacterium avium complex bacteremia in patients with AIDS.

The individual antibacterial activities of clofazimine, ethambutol, and rifampin in the treatment of Mycobacterium avium complex bacteremia in patients with AIDS were determined. Sixty human immunodeficiency virus 1-infected patients who had at least one blood culture positive for M. avium complex were randomized to receive either clofazimine (200 mg), ethambutol (15 mg/kg), or rifampin (600 mg) once daily for 4 weeks. Only ethambutol resulted in a statistically significant reduction in the level of mycobacteremia. The median change in individual baseline colony counts was -0.60 log10 cfu/mL after 4 weeks of ethambutol (P = .046). In contrast, median changes in individual baseline colony counts were -0.2 log10 cfu/mL and +0.2 log10 cfu/mL for clofazimine and rifampin, respectively (both, P > .4). Ethambutol had greater antibacterial activity, as determined by changes in the level of mycobacteremia, than either rifampin or clofazimine, supporting its continued use in combination with other agents in the treatment of M. avium infection.

Multicenter in vitro comparative study of fluoroquinolones after four years of widespread clinical use.

In vitro activities of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, and seven other oral antimicrobials including amoxicillin-clavulanic acid (A/C), oxacillin, cefaclor, cefixime, cefuroxime, erythromycin, and trimethoprim-sulfamethoxazole (T/S) were evaluated against 1708 fresh bacterial isolates from four hospital laboratories approximately 4 years after the introduction of ciprofloxacin. T/S and ofloxacin had the lowest MIC90s and greatest percentage of susceptible strains overall, followed by the other three quinolones. Quinolones were the most active drugs tested against Gram-negative bacteria, with little variation in the activity among the four compounds against most species. Quinolone resistance was detected to some degree in the majority of Gram-negative species tested, with Pseudomonas, Acinetobacter, Xanthomonas, and Providencia demonstrating the highest percentage of resistant strains. Ofloxacin and ciprofloxacin were relatively more active against Gram-positive bacteria than were fleroxacin and lomefloxacin, but T/S and A/C had more susceptible strains than any of the quinolones. Oxacillin-resistant staphylococci, enterococci, and streptococci exhibited the least quinolone susceptibility. This study showed that while resistance is developing among several previously susceptible bacterial species, quinolones remain important alternatives for the oral treatment of many types of infections. Actions to prevent or limit resistance will be important to maintain the viability of the quinolones as therapeutic agents in both hospital and community environments.

Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. The Mupirocin Collaborative Study Group.

Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86-0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus.

Epidemiology and infectious complications of human immunodeficiency virus antibody positive patients.

From July 1, 1991 to March 31, 1992, 156 patients (pts) with positive antibody titers to the human immunodeficiency virus (HIV) were seen in our clinic. A retrospective review of the epidemiology and infectious complications of these patients is presented. There were 129 males and 27 females (4.8:1, ratio). Only 10/156 (12.8%) were non-whites (13 blacks and 7 hispanics). The majority, 126 (80.7%), were 25 to 44 years old. The most common risk factor was homosexuality or bisexuality 100 (64.1%), followed by heterosexual acquisition 25 (16%), intravenous drug abuse 23 (13.7%), unknown 6 (3.8%) and transfusion-related 3 (1.9%). Sixty-five pts had no infections. In the remaining 91 pts, the infections noted were: candidiasis (54 pts); Pneumocystis carinii pneumonia (25 pts); Herpes simplex (13 pts); cytomegalovirus (CMV) retinitis (11 pts) and CMV esophagitis (1 pt), central nervous system toxoplasmosis (8); Herpes zoster (6 pts); cryptococcal meningitis (5 pts); Mycobacterium avium complex bacteremia (4 pts); Molluscum contagiosum, hepatitis-B, staphylococcal infection, perirectal abscess and oral hairy leukoplakia (2 pts each); syphilis, cryptosporidiosis, nocardiosis, histoplasmosis and laryngeal papillomatosis (1 pt each). Infections were multiple in 57/91 (62%) pts and tend to occur more often when the helper cells are < 200 47/57 (82%) pts. Appropriate antimicrobials for prophylaxis and maintenance therapy appeared to decrease the occurrence or relapse of infections such as pneumocystosis, candidiasis, cryptococcosis, tuberculosis and toxoplasmosis.

Reduced urosepsis in a veterans' hospital.

A three-year study of infecting organisms in a 600-bed university hospital revealed that despite an overall high incidence of urinary sepsis by resistant organisms only a small portion (3.5%) occurred on the urology service. Possible explanatory causes for this low infection rate included avoidance of cross infection from known pools of resistant organisms, short hospital stays, and close adherence to strictly aseptic techniques in handling patient's tubes and collecting devices. Simple measures provided protection from costly, debilitating disease.

Twice daily intramuscular imipenem/cilastatin in the treatment of skin and soft tissue infections.

One hundred and two patients were enrolled in an open-label evaluation of intramuscular imipenem/cilastatin using doses of either 500 or 750 mg every 12 h in the treatment of mild to moderately severe skin and soft tissue infections. Seventy-four of 102 patients were clinically evaluable. Thirty-one patients had abscesses, 20 had cellulitis and 23 had wound infections. One hundred seventy-eight isolates were recovered from these 74 patients (average 2.4 isolates/patient). Sixty of 74 evaluable patients (82%) were cured; 12 of 74 (16%) were improved. Two patients failed to improve. Therapy was well tolerated. Adverse effects occurred in 8 patients. All of these effects were minor, and none required discontinuation of therapy. Eighty-two percent of patients reported no pain with injections. Therapy did not need to be interrupted or discontinued in the remaining 18% of patients reporting moderate local pain with injections. Peak and trough serum imipenem levels were measured in 15 patients receiving a 500-mg intramuscular dose of imipenem/cilastatin. The mean peak imipenem concentration in 15 patients was 10.7 micrograms/ml (range 3.3-17.8); the mean trough concentration was 2.1 micrograms/ml (range 0.8-4.9). The trough levels were higher than those found in healthy volunteers and may reflect the age and mild renal dysfunction in this group of treated patients. Imipenem/cilastatin used for mild or moderate skin and soft tissue infections was both efficacious and well tolerated. Intramuscular therapy with this agent offers advantages over intravenous therapy because of its long apparent half-life and pharmacokinetics.

A multicenter trial comparing the efficacy and safety of cefuroxime axetil and cefaclor in pneumonia of adults.

The 185 hospitalized patients (aged 19 to 95 years) with pneumonia were randomly assigned to receive 500 mg of cefuroxime axetil orally (250 mg q12h), 1,000 mg of cefuroxime axetil orally (500 mg q12h), or 1,500 mg of cefaclor orally (500 mg q8h), daily, for a mean of nine days. Among the 151 evaluable patients, clinical cure was noted in 58% of the 500-mg cefuroxime axetil group, 94% of the 1,000-mg cefuroxime axetil group, and 88% of the cefaclor group, and clinical improvement in 32%, 4%, and 9%. Bacteriologic outcome was similar in the three groups. Adverse events were minor and comparable among the treatment groups. Cefuroxime axetil is a safe and effective oral antimicrobial for the treatment of pneumonia in adults.