Ajay K. Sethi

Association between Adherence to Antiretroviral Therapy and Human Immunodeficiency Virus Drug Resistance

Nonadherence to highly active antiretroviral therapy (HAART) is a major cause of human immunodeficiency virus (HIV) drug resistance; however the level of nonadherence associated with the greatest risk of resistance is unknown. Beginning in February 2000, 195 patients at the Johns Hopkins Outpatient Center (Baltimore, MD) who were receiving HAART and who had HIV loads of <500 copies/mL were recruited into a cohort study and observed for 1 year. At each visit, adherence to HAART was assessed and plasma samples were obtained and stored for resistance testing, if indicated. The overall incidence of viral rebound with clinically significant resistance was 14.5 cases per 100 person-years. By multivariate Cox proportional hazards regression, a cumulative adherence of 70%-89%, a CD4 cell nadir of <200 cells/microL, and the missing of a scheduled clinic visit in the past month were independently associated with an increased hazard of viral rebound with clinically significant resistance. Clinicians and patients must set high adherence goals to avoid the development of resistance.

Reduction of Clostridium Difficile and vancomycin-resistant Enterococcus contamination of environmental surfaces after an intervention to improve cleaning methods

BackgroundContaminated environmental surfaces may play an important role in transmission of some healthcare-associated pathogens. In this study, we assessed the adequacy of cleaning practices in rooms of patients with Clostridium difficile-associated diarrhea (CDAD) and vancomycin-resistant Enterococcus (VRE) colonization or infection and examined whether an intervention would result in improved decontamination of surfaces.MethodsDuring a 6-week period, we cultured commonly touched surfaces (i.e. bedrails, telephones, call buttons, door knobs, toilet seats, and bedside tables) in rooms of patients with CDAD and VRE colonization or infection before and after housekeeping cleaning, and again after disinfection with 10% bleach performed by the research staff. After the housekeeping staff received education and feedback, additional cultures were collected before and after housekeeping cleaning during a 10-week follow-up period.ResultsOf the 17 rooms of patients with VRE colonization or infection, 16 (94%) had one or more positive environmental cultures before cleaning versus 12 (71%) after housekeeping cleaning (p = 0.125), whereas none had positive cultures after bleach disinfection by the research staff (p < 0.001). Of the 9 rooms of patients with CDAD, 100% had positive cultures prior to cleaning versus 7 (78%) after housekeeping cleaning (p = 0.50), whereas only 1 (11%) had positive cultures after bleach disinfection by research staff (p = 0.031). After an educational intervention, rates of environmental contamination after housekeeping cleaning were significantly reduced.ConclusionOur findings provide additional evidence that simple educational interventions directed at housekeeping staff can result in improved decontamination of environmental surfaces. Such interventions should include efforts to monitor cleaning and disinfection practices and provide feedback to the housekeeping staff.

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users.

ObjectiveStudies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. MethodsA cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society–USA panel (IAS–USA) guidelines. ResultsBy 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. ConclusionsSelf-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.

Persistence of Skin Contamination and Environmental Shedding of Clostridium difficile during and after Treatment of C. difficile Infection

BACKGROUND Current guidelines for control of Clostridium difficile infection (CDI) suggest that contact precautions be discontinued after diarrhea resolves. However, limited information is available regarding the frequency of skin contamination and environmental shedding of C. difficile during and after treatment. DESIGN We conducted a 9-month prospective, observational study involving 52 patients receiving therapy for CDI. Stool samples, skin (chest and abdomen) samples, and samples from environmental sites were cultured for C. difficile before, during, and after treatment. Polymerase chain reaction ribotyping was performed to determine the relatedness of stool, skin, and environmental isolates. RESULTS Fifty-two patients with CDI were studied. C. difficile was suppressed to undetectable levels in stool samples from most patients during treatment; however, 1-4 weeks after treatment, 56% of patients who had samples tested were asymptomatic carriers of C. difficile. The frequencies of skin contamination and environmental shedding remained high at the time of resolution of diarrhea (60% and 37%, respectively), were lower at the end of treatment (32% and 14%, respectively), and again increased 1-4 weeks after treatment (58% and 50%, respectively). Skin and environmental contamination after treatment was associated with use of antibiotics for non-CDI indications. Ninety-four percent of skin isolates and 82% of environmental isolates were genetically identical to concurrent stool isolates. CONCLUSIONS Skin contamination and environmental shedding of C. difficile often persist at the time of resolution of diarrhea, and recurrent shedding is common 1-4 weeks after therapy. These results provide support for the recommendation that contact precautions be continued until hospital discharge if rates of CDI remain high despite implementation of standard infection-control measures.

Both Oral Metronidazole and Oral Vancomycin Promote Persistent Overgrowth of Vancomycin-Resistant Enterococci during Treatment of Clostridium difficile-Associated Disease

ABSTRACT For treatment of mild to moderate Clostridium difficile-associated disease (CDAD), oral metronidazole has been recommended as the preferred agent, in part due to concern that vancomycin may be more likely to promote colonization by vancomycin-resistant enterococci (VRE). We performed a prospective observational study to examine the effects of oral metronidazole or vancomycin treatment of CDAD on acquisition and concentration of VRE stool colonization. Before, during, and after 90 courses of CDAD therapy, stool samples were cultured for VRE, and the concentrations were quantified. Eighty-seven subjects (97%) had received antibiotics within the past month. For 56 treatment courses in which preexisting VRE colonization was present, metronidazole (n = 37 courses) and vancomycin (n = 19 courses), each promoted persistent VRE overgrowth during therapy, and the concentration decreased significantly in both groups by ∼2 weeks after completion of treatment (P <0.049). For 34 treatment courses in which baseline cultures were negative for VRE, new detection of VRE stool colonization occurred during 3 (14%) of the 22 courses of metronidazole and 1 (8%) of the 12 courses of vancomycin (P = 1.0). These results demonstrate that both oral metronidazole and oral vancomycin promote the overgrowth of VRE during treatment of CDAD. New CDAD treatments are needed that are less likely to disrupt the intestinal microflora and promote overgrowth of healthcare-associated pathogens.

Comparison of Clinical and Microbiological Response to Treatment of Clostridium difficile–Associated Disease with Metronidazole and Vancomycin

BACKGROUND There have been recent reports of frequent treatment failure associated with the use of metronidazole for treatment of Clostridium difficile-associated disease. We tested the hypothesis that treatment failure with metronidazole is associated with a suboptimal microbiological response in comparison with that of vancomycin. METHODS We conducted a 9-month prospective observational study of patients with C. difficile-associated disease. Cox proportional hazards models were used to compare metronidazole-treated and vancomycin-treated patients in terms of time to resolution of diarrhea and time to reduction of C. difficile in stool to an undetectable level. RESULTS Of 52 study patients with C. difficile-associated disease, 34 (65%) received initial therapy with oral metronidazole, and 18 (35%) received initial therapy with oral vancomycin. Diarrhea resolved in >90% of patients who completed 10 days of treatment with either agent. However, vancomycin-treated patients were more likely to develop undetectable levels of C. difficile (adjusted hazard ratio, 3.99; 95% confidence interval, 1.41-11.3;P = .009) and to have resolution of diarrhea (adjusted hazard ratio, 4.17; 95% confidence interval, 1.53-11.40;P = .005) during the first 5 days of therapy. Ten metronidazole-treated patients (29%) had their treatment changed to oral vancomycin because of persistent symptoms. Seven (70%) of these 10 patients had <1 log reduction in C.difficile concentration; however, only 4 had completed > or = 6 days of metronidazole treatment at the time of the treatment change. CONCLUSION In an observational study with a limited number of subjects, a majority of patients with C. difficile-associated disease responded to therapy with metronidazole or vancomycin. Failure with metronidazole treatment may be attributable to a slower and less consistent microbiological response than that with oral vancomycin treatment.

An Environmental Disinfection Odyssey: Evaluation of Sequential Interventions to Improve Disinfection of Clostridium difficile Isolation Rooms

OBJECTIVE. Effective disinfection of hospital rooms after discharge of patients with Clostridium difficile infection (CDI) is necessary to prevent transmission. We evaluated the impact of sequential cleaning and disinfection interventions by culturing high-touch surfaces in CDI rooms after cleaning. DESIGN. Prospective intervention. SETTING. A Veterans Affairs hospital. INTERVENTIONS. During a 21-month period, 3 sequential tiered interventions were implemented: (1) fluorescent markers to provide monitoring and feedback on thoroughness of cleaning facility-wide, (2) addition of an automated ultraviolet radiation device for adjunctive disinfection of CDI rooms, and (3) enhanced standard disinfection of CDI rooms, including a dedicated daily disinfection team and implementation of a process requiring supervisory assessment and clearance of terminally cleaned CDI rooms. To determine the impact of the interventions, cultures were obtained from CDI rooms after cleaning and disinfection. RESULTS. The fluorescent marker intervention improved the thoroughness of cleaning of high-touch surfaces (from 47% to 81% marker removal; P < .0001). Relative to the baseline period, the prevalence of positive cultures from CDI rooms was reduced by 14% (P=.024), 48% (P <.001), and 89% (P=.006) with interventions 1, 2, and 3, respectively. During the baseline period, 67% of CDI rooms had positive cultures after disinfection, whereas during interventions periods 1, 2, and 3 the percentages of CDI rooms with positive cultures after disinfection were reduced to 57%, 35%, and 7%, respectively. CONCLUSIONS. An intervention that included formation of a dedicated daily disinfection team and implementation of a standardized process for clearing CDI rooms achieved consistent CDI room disinfection. Culturing of CDI rooms provides a valuable tool to drive improvements in environmental disinfection.

Quality of life and social support among patients receiving antiretroviral therapy in Western Uganda

Abstract Quality of life (QOL) among patients with HIV/AIDS has been shown to improve once treatment with antiretroviral therapy (ART) has been initiated. We conducted a cross-sectional study in Western Uganda to examine the factors associated with QOL among patients who had received ART for the duration of at least six months. We interviewed 330 patients attending the HIV/AIDS clinic at two government-supported hospitals in Western Uganda. We measured QOL using a culturally adapted version of the Medical Outcomes Study (MOS-HIV) tool and calculated the physical health summary (PHS) and mental health summary (MHS) scores. In addition, data were collected on sociodemographic factors, three-day self-reported adherence, social support, sexual behavior, CD4 count and viral load. Informational social support was significantly positively correlated with PHS (p=0.001) and MHS (p=0.002). Affectionate support was also significantly positively correlated to PHS (p=0.05) and MHS (p=0.03) but tangible support was not (PHS p value=0.85 and MHS p value=0.31). In the univariate analysis, older age, rural dwelling, alcohol use, CD4 count less than 200, and ART duration of less than one year were significantly associated with lower PHS scores. Lower PHS scores were also associated with sexual inactivity. In multivariate analysis, higher scores on informational social support and CD4≥200 were associated with higher PHS score and past or recent alcohol consumption was associated with lower scores on MHS. Optimizing ART to restore CD4 count and provision of informational and affectionate social support but not tangible support, to HIV/AIDS patients may improve their QOL.

Sustained reduction in inappropriate treatment of asymptomatic bacteriuria in a long-term care facility through an educational intervention

BACKGROUND In long-term care facilities, treatment of asymptomatic bacteriuria (ASB) is common. However, randomized, controlled trials suggest that such treatment offers no benefit and may promote antimicrobial resistance. METHODS For 3 months before and 30 months after instituting an educational intervention, we monitored the appropriateness of urine culture collection and antibiotic treatment based on published guidelines and examined the effect on total antimicrobial use. The intervention included education of nursing staff to discourage the collection of urine cultures in the absence of symptoms suggestive of urinary tract infection and of primary care practitioners to not treat ASB. RESULTS In preintervention period, 23 of 38 (61%) antibiotic regimens prescribed for urinary tract indications were for ASB. In the 6 months after the intervention, inappropriate submission of urine cultures decreased from 2.6 to 0.9 per 1000 patient-days (P < .0001), overall rate of treatment of ASB was reduced from 1.7 to 0.6 per 1000 patient-days (P = .0017), and total antimicrobial days of therapy were reduced from 167.7 to 117.4 per 1000 patient-days (P < .001). These reductions were maintained for 30 months after beginning the intervention. CONCLUSION Educational interventions requiring minimal resources can result in sustained reductions in inappropriate treatment of ASB in long-term care and decreased total antimicrobial use. Education of the nursing staff regarding appropriate criteria for requesting urine cultures should be a component of such interventions.

Unnecessary use of fluoroquinolone antibiotics in hospitalized patients

BackgroundFluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for Clostridium difficile infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use.MethodsWe conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy.ResultsOf 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens).ConclusionsIn our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for management of urinary syndromes could significantly reduce overuse of fluoroquinolones.