Kwan Kew Lai

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of ‘covert’ virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

Failure to eradicate vancomycin-resistant enterococci in a university hospital and the cost of barrier precautions.

OBJECTIVE To describe the effect of infection control interventions on the incidence of vancomycin-resistant enterococci (VRE), the utility of pharyngeal cultures for surveillance for VRE colonization, and the cost of barrier precautions. DESIGN Evaluation of the occurrence of VRE infection or colonization, rates of vancomycin use, results of surveillance cultures before and after interventions, and the cost of increased barrier precautions. SETTING University of Massachusetts Medical Center, a 347-bed tertiary-care teaching hospital with eight intensive-care units, one burn unit, and one bone marrow transplant unit. PARTICIPANTS Patients in the intensive-care units and staff who were involved with patients colonized or infected with VRE. METHODS Infection control interventions included placement of patients with VRE in private rooms, strict contact isolation, cohorting of patient and nursing staff, prohibiting of equipment sharing, and monitoring of compliance with the vancomycin restriction policy, with hand washing, and of the adequacy of environmental cleaning. Both rectal and pharyngeal cultures were obtained from patients at the beginning of the outbreak, and the utility of pharyngeal cultures was evaluated. The cost of barrier precautions was estimated by comparing the cost of glove and gown use before and after the outbreak began. RESULTS The interventions decreased the number of new cases of VRE, but total eradication of VRE was not achieved. Compliance with the room-cleaning protocol was 91% (141/155 observations). Hand washing following interaction with patients who were not in isolation was 51%, vs 100% for patients in isolation. Overall, handwashing compliance was 71% (319/449): 56% (130/231) for physicians and 86% (187/218) for nurses (P<.0001). The mean number of doses of vancomycin dispensed per 1,000 patient days decreased from 145 to 114 per 1,000 patient days (P<.001). Compliance with vancomycin-use guidelines was 85%. Forty-six (77%) of 60 surveillance rectal swabs yielded enterococci, as compared to only 4 (11%) of 36 pharyngeal cultures (P<.0001). Expenses on glove and gowns alone increased by over

Infections Associated with Implantable Cardioverter Defibrillators Placed Transvenously and via Thoracotomies: Epidemiology, Infection Control, and Management

11,000 per year since the epidemic began. CONCLUSIONS Implementation of the various infection control measures did not eradicate VRE cases from the hospital. Rectal cultures were more useful than pharyngeal cultures for surveillance of VRE. Controlling VRE epidemics can be costly.

Influenza in Human Immunodeficiency Virus-Infected Patients during the 1997–1998 Influenza Season

In 1993, the incidence of infection associated with implantable cardioverter defibrillators (ICDs) excluding generator, lead, and patch placements was 16.7% at our institution. Eighty-eight percent of the ICD implantations were two-staged procedures: the cardiologists performed the electrophysiologic studies in their laboratories, and implantations were performed in the operating rooms a few hours to a few days later by cardiothoracic surgeons. In 1994, both the electrophysiologic studies and ICD implantations were performed in the operating rooms without waiting periods. From 1993 to 1995, the proportion of ICDs placed transvenously increased from 56% to 100%, whereas the proportion of two-staged ICD placements decreased from 88% to zero. From 1992 to 1993 the infection rate decreased concomitantly from 16.7% to zero. From 1992 through 1995, the infection rate for implantable ICDs alone was 4.8%, and the overall infection rate for implantable ICDs (including generator, lead, and patch placements) was 6.9%, comparable to the rate reported in the literature (2.2% to 7.2%). The elimination of the two-stage procedure and the increased proportion of transvenously placed ICDs has contributed to the decrease in infection rate.

Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control.

A cluster of cases of severe influenzal disease was recognized in HIV-infected individuals during the 1997-1998 influenza season. Both primary influenza pneumonia and concomitant viral and bacterial pneumonia were found.

Long-Term Laboratory Contamination by Mycobacterium abscessus Resulting in Two Pseudo-Outbreaks: Recognition with Use of Random Amplified Polymorphic DNA (RAPD) Polymerase Chain Reaction

OBJECTIVES To evaluate the effectiveness of specific infection control measures on the incidence of Clostridium difficile-associated diarrhea (CDAD) and to identify risk factors for its development. SETTING 370-bed, tertiary-care teaching hospital with approximately 12,000 to 15,000 admissions per year. METHODS Several infection control measures were implemented in 1991 and 1992, and the attack rates of CDAD were calculated quarterly. Antibiotic use for 1988 through 1993 was analyzed. A case-control study was conducted from January 1992 to December 1992 to identify risk factors for acquisition of CDAD. RESULTS From 1989 to 1992, the attack rate of CDAD increased from 0.49% to 2.25%. An increase in antibiotic use preceded the rise in the incidence of CDAD in 1991. Despite implementation of various infection control measures, the attack rate decreased to 1.32% in 1993, but did not return to baseline. Ninety-two cases and 78 controls (patients with diarrhea but with negative toxin assay) were studied. By univariate analysis, history of prior respiratory tract infections (odds ratio [OR], 3.6; 95% confidence interval [CI95], 1.2-10.4), the number of antibiotics, and the duration of exposure to second-generation cephalosporins (OR, 3.55; CI95, 1.47-9.41) and to ciprofloxacin (OR, 7.27; CI95, 1.13-166.0) were related significantly to the development of CDAD. By stepwise logistic regression analysis, only exposure to antibiotics and prior respiratory tract infections (P = .0001 and .0203, respectively) were found to be significant. CONCLUSION Antibiotic pressure might have contributed to failure of infection control measures to reduce the incidence of CDAD to baseline.

Impact of a program of intensive surveillance and interventions targeting ventilated patients in the reduction of ventilator-associated pneumonia and its cost-effectiveness

Beginning in 1993, an increase in clinical isolates of Mycobacterium abscessus was observed in a single hospital microbiology laboratory. This involved a cluster of four patients in June 1993 and five patients and a quality-control culture of distilled water in May 1994. Twenty-three M. abscessus isolates recovered between 1991 and 1996 were compared by random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Sixteen of 21 clinical isolates recovered over a 6-year period and the distilled water isolate had identical RAPD-PCR patterns consistent with a single strain or clone. Only six of 15 patients had findings suggestive of clinical disease. Since the use of in-house-prepared distilled water was discontinued, no further laboratory contamination of clinical specimens has been observed. Molecular typing was the key to defining distilled water as the source of this pseudo-outbreak. Recognition of such outbreaks is important for prevention of unnecessary therapeutic and diagnostic interventions.

The epidemiology of fecal carriage of vancomycin-resistant enterococci

OBJECTIVE We hypothesized that a program of prospective intensive surveillance for ventilator-associated pneumonia (VAP) and concomitant implementations of multimodal, multidisciplinary preventive and intervention strategies would result in a reduction in the incidence of VAP and would be cost-effective. SETTING Medical and surgical intensive care units (ICUs) in a university teaching hospital. INTERVENTIONS All ventilated patients in the medical and surgical ICUs were monitored for VAP from January 1997 through December 1998. Interventions including elevation of the head of the bed, use of sterile water and replacement of stopcocks with enteral valves for nasogastric feeding tubes, and prolongation of changing of in-line suction catheters from 24 hours to as needed were implemented. RESULTS The rates of VAP decreased by 10.8/1,000 ventilator-days in the medical ICU (CI95, 4.65-16.91) and by 17.2/1,000 ventilator-days in the surgical ICU (CI95, 2.85-31.56) when they were compared for 1997 and 1998. With the use of the estimated cost of a VAP of dollars 4,947 from the literature, the reduction resulted in cost savings of dollars 178,092 and dollars 148,410 in the medical and surgical ICUs, respectively, for a total of dollars 326,482. In addition, dollars 25,497 was saved due to the lengthening of the time for the change of in-line suction catheters, resulting in a cost savings of dollars 351,979. This total cost savings of dollars 351,979 minus the cost of enteral valves of dollars 2,100 resulted in total net savings of dollars 349,899. CONCLUSION Intensive surveillance and interventions targeted at ventilated patients resulted in reduction of VAP and appeared to be cost-effective.

Impact of alcohol-based, waterless hand antiseptic on the incidence of infection and colonization with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci

An outbreak of vancomycin-resistant enterococci (VRE) began at the University of Massachusetts Medical Center in May 1993. As of September 1995, we had a total of 253 patients infected or colonized with VRE, with consequent increasing demand for private rooms. We analyzed results of surveillance cultures for VRE of 49 patients known to be colonized or infected with VRE. Of these, 34 (70%) were classified as persistent carriers, defined as patients with at least three consecutively positive cultures from any site taken over at least a 2-week period. The length of carriage varied from 19 to 303 days (median, 41 days); 11 patients were converters, defined as patients with three consecutive negative cultures from all previously colonized sites taken over a 3-week period. These patients were free of VRE for 39 to 421 days (median, 142 days). Four were recolonizers after they were documented to be clear of VRE for 33 to 106 days. VRE carriage tends to be prolonged, and hospitalization of patients with VRE will require continued isolation and contact precautions for control of transmission.

Rapid eradication of a cluster of Serratia marcescens in a neonatal intensive care unit: use of epidemiologic chromosome profiling by pulsed-field gel electrophoresis.

OBJECTIVE Colonized and infected inpatients are major reservoirs for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), and transient carriage of these pathogens on the hands of healthcare workers remains the most common mechanism of patient-to-patient transmission. We hypothesized that use of alcohol-based, waterless hand antiseptic would lower the incidence of colonization and/or infection with MRSA and VRE. METHODS On June 19, 2001, alcohol hand antiseptic was introduced at the University campus and not the nearby Memorial campus of the University of Massachusetts Medical School (Worcester, MA), allowing us to evaluate the impact of this antiseptic on the incidence of MRSA and VRE colonization and infection. From January 1 through December 31, 2001, the incidence of MRSA colonization or infection was compared between the 2 campuses before and after the hand antiseptic was introduced. Its effect on VRE colonization and infection was only studied in the medical intensive care unit at the University campus. RESULTS At the University campus, the incidence of MRSA colonization or infection decreased from 1.26 cases/1,000 patient-days before the intervention to 0.75 cases/1,000 patient-days after the intervention, for a 1.46-fold decrease (95% confidence interval, 1.04-2.58; P = .037). At the Memorial campus, the incidence of MRSA colonization or infection remained virtually unchanged, from 0.34 cases/1,000 patient-days to 0.49 cases/1,000 patient-days during the same period. However, a separate analysis of the University campus data that controlled for proximity to prevalent cases did not show a significant improvement in the rates of infection or colonization. The incidence of nosocomial VRE colonization or infection before and after the hand antiseptic decreased from 12.0 cases/1,000 patient-days to 3.0 cases/1,000 patient-days, a 2.25-fold decrease (P = .018). Compliance with rectal surveillance for detection of VRE was 86% before and 84% after implementation of the hand antiseptic intervention. The prevalences of VRE cases during these 2 periods were 25% and 29%, respectively (P = .017). CONCLUSIONS Alcohol hand antiseptic appears to be effective in controlling the transmission of VRE. However, after controlling for proximity to prevalent cases (ie, for clustering), it does not appear to be more effective than standard methods for controlling MRSA. Further controlled studies are needed to evaluate its effectiveness.