Severity of illness scoring systems in patients with bacteraemic pneumococcal pneumonia: implications for the intensive care unit care.

Severity of illness scoring systems are useful for decisions on the management of patients with community-acquired pneumonia (CAP), including assessing the need for intensified therapy and monitoring, or for intensive care unit (ICU) admission. We compared the accuracy of the Pneumonia Severity Index (PSI), the CURB-65 and CRB-65 score, the modified-American Thoracic Society score (ATS), the IDSA/ATS guidelines and the Pitt Bacteraemia score (PBS) in evaluating severity of illness in 766 patients with bacteraemic pneumococcal pneumonia. We evaluated the sensitivity and specificity, the positive predictive value (PPV) and the negative predictive value (NPV) and the accuracy of the classification in predicting 14-day mortality. The PSI and the IDSA/ATS guidelines were the most sensitive whereas the PBS and modified-ATS scoring systems were the most specific in predicting mortality. The NPV was comparable for all four scoring systems (all above 90%), but the PPV was highest for PBS (54.2%) and lowest for PSI (23.2%). The predictive accuracy and discriminating power as measured by the receiver-operating characteristic (ROC) curve was highest for the PBS. Both the modified-ATS and the PBS scoring systems identified those patients who might benefit most from intensified care and monitoring. The PBS and modified-ATS proved superior to the IDSA/ATS guidelines, CURB-65 and CRB-65 with respect to their specificity and PPV. The low PPV of the PSI rendered it not usable as a parameter for decision-making in severely-ill patients with pneumococcal bacteraemia.

Prevention of posttransplant cytomegalovirus disease and related outcomes with valganciclovir: a systematic review.

The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT recipients were synthesized for descriptive analysis. CMV disease occurred in 2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and prophylaxis, respectively. Although the incidence of early-onset (90 days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic group, respectively. On the contrary, no patients developed late-onset CMV disease in preemptive group. Both approaches with valganciclovir have successfully decreased CMV disease in SOT recipients. Late-onset CMV disease is a complication observed uniquely with valganciclovir prophylaxis, particularly in R-/D+ patients, but not with preemptive therapy.

Antifungal management practices in liver transplant recipients.

We sought to determine the approach to antifungal prophylaxis, and diagnostic and therapeutic practices for the management of invasive aspergillosis in liver transplant recipients. Data were collected by an electronic survey questionnaire sent to all active liver transplant programs in North America; 63% (67/106) of the sites completed the survey. Overall, 91% of the sites employed antifungal prophylaxis; 28% used universal prophylaxis and 72% targeted it toward high-risk patients. Fluconazole was the most commonly used agent for universal and targeted prophylaxis. The leading choice for mold-active agents for antifungal prophylaxis was the echinocandins. Combination therapy was used as primary therapy for invasive aspergillosis in 47%, and as salvage in 80%. Thus, a vast majority of the surveyed programs employ antifungal prophylaxis and most use targeted prophylaxis. Consideration of these practices could guide clinical trial design to optimize antifungal prophylaxis in these patients. Our findings also merit investigations to better define the role of diagnostic assays and combination therapeutic strategies for invasive aspergillosis in liver transplant recipients.

A survey of CMV prevention strategies after liver transplantation.

The degree of variability in the use of CMV prevention strategies and choice of antiviral regimens among LT centers has not been previously investigated. An electronic survey on current CMV prevention strategies was sent to all US and Canadian LT centers. A total of 58 (53%) centers completed the survey. Most use CMV PCR for screening or diagnosis. Prophylaxis was the most common prevention strategy for all donor/recipient subtypes except D-/R- who often receive no prophylaxis. Prophylaxis was usually given for 3 months after LT with valganciclovir the most frequently used agent. In the small percentage of centers utilizing the preemptive approach, monitoring for CMV was typically performed with PCR for 3 months and valganciclovir was most frequently used for treatment of detectable CMV viremia. In conclusion, the majority of LT centers utilize CMV prophylaxis over other strategies. Valganciclovir is the most commonly used agent for both antiviral prophylaxis and treatment of CMV viremia in the preemptive approach.

Bacteremia in lung transplant recipients in the current era.

Current trends in the epidemiology, outcome and variables influencing mortality in bacteremic lung transplant recipients have not been fully described. We prospectively studied bacteremias in lung transplant recipients in a multicenter study between 2000-2004. Bacteremia was documented in 56 lung transplant recipients, an average of 172 days after transplantation. Multiple antibiotic resistance was documented in 48% of the isolates; these included 57% of the Gram-negative and 38% of the Gram-positive bacteria. Pulmonary infection was the most common source of resistant gram-negative bacteremias. Mortality rate at 28 days after the onset of bacteremia was 25% (14/56). Mechanical ventilation and abnormal mental status correlated independently with higher mortality (p < 0.05 for both variables). Bacteremia remains a significant complication in lung transplant recipients and is associated with considerable mortality. Recognition of variables portending a high risk for antibiotic resistance and for poor outcome has implications relevant for optimizing antibiotic prescription and for improving outcomes in lung transplant recipients.

T-helper cell responses in liver transplant recipients: correlation with cytomegalovirus and other major infections.

Mitogen concanavalin A (ConA) response and cytomegalovirus (CMV)-specific memory response were assessed in 24 liver transplant recipients and compared with healthy subjects. Transplant recipients as compared to healthy subjects had a lower CMV memory response at 2 weeks (P=0.023), and at 1 month (P=0.06), but a comparable response at 3 months. CMV recipient+/donor+(R+/D+) patients had the greatest increase in CMV-specific memory response at 2-3 months as compared to all other groups. Within this R+/D+ group, CMV-specific memory response was significantly more robust in patients who never had CMV infection as compared to those who developed CMV infection (P=0.035). ConA response at 2 weeks was significantly lower in patients with major infections as compared to those without them (SI 5.4 vs. 38.1, P=0.039). Thus, reconstitution of CMV-specific T-helper cell response was distinct for subsets of liver transplant recipients based on the recipient and donor CMV serostatus. Impairment in proliferative response to ConA identified a subgroup of patients with major infections after liver transplantation.

Changing epidemiology and predictors of mortality in patients with spontaneous bacterial peritonitis at a liver transplant unit.

OBJECTIVES: To determine whether antimicrobial resistance in pathogens and outcome in patients with spontaneous bacterial peritonitis (SBP) has evolved over time. METHODS: Sixty-one consecutive episodes of SBP were studied in patients with end-stage liver disease undergoing evaluation for liver transplantation between 1991 and 2001. Patients were dichotomized into a cohort between 1991 and 1995 (the earlier cohort) and 1996-2001 (the later cohort). RESULTS: Overall, 19% of all bacteria were multiply-antibiotic resistant. The frequency of multiple-antibiotic resistance in bacteria increased from 8.3% to 38.5% in the earlier as compared to the later cohort (P = 0.07). Overall, mortality at 30 days in the study patients was 26% and had remained unchanged between the two cohorts. The mortality rate was significantly higher in patients with multiply-antibiotic-resistant bacteria than in those with other bacteria (P = 0.045). However, the Child-Pugh score (P = 0.003), and renal failure (P = 0.04) were the only independently significant predictors of mortality in patients with SBP. CONCLUSIONS: Mortality in patients with end-stage liver disease who developed SBP has remained unchanged over the last decade. Although multiple-antibiotic resistance in bacteria causing SBP has increased over time, the severity of hepatic and renal dysfunction were the predominant determinants of outcome in these patients.

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study.

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.

Seasonal pattern of early mortality and infectious complications in liver transplant recipients.

Seasonal variation has been documented in the frequency and attributable mortality of a number of medical illnesses and infections in the nontransplantation setting. Whether similar trends exist in transplant recipients is not known. Seasonal rates of overall and early mortality and contributory variables stratified by season were assessed in 190 consecutive liver transplant recipients who underwent transplantation over a 10-year period. The frequency of infectious complications and rejection was also assessed and stratified by season of transplantation. Early (deaths occurring in the first year posttransplantation), but not overall, mortality correlated significantly with seasonality. Of patients with early mortality, 43% (13 of 30 patients) died in winter; 23% (7 of 30 patients), in spring; 13% (4 of 30 patients), in summer; and 20% (6 of 30 patients), in fall. The frequency of deaths in winter was significantly greater than for all other seasons (P = .022). The high wintertime mortality could not be explained by previously recognized risk factors portending a poor outcome, e.g., United Network for Organ Sharing status, Child-Pugh score, surgical time, blood loss, pretransplantation and posttransplantation dialysis, infections, rejection, or increased immunosuppression. Strong trends toward a higher rate of cytomegalovirus disease in patients who underwent transplantation in fall (P = .09) and bacterial infections in those who underwent transplantation in winter were documented (P = .09). There was no correlation between seasonality and rejection. Early mortality in winter in liver transplant recipients was significantly greater than if the deaths were totally random. Whether the seasonal clustering of deaths and infections is triggered by respiratory viruses, yet unrecognized viruses, or unknown exogenous factors remains to be determined.

Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.

Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients.

Dyslipidaemia in HIV-infected patients: association with adherence to potent antiretroviral therapy.

Metabolic complications are being increasingly recognized among HIV-infected patients treated with potent combination antiretroviral therapies. We sought to assess the association of dyslipidaemia with adherence to protease inhibitor (PI) therapy and with the markers of clinical response to antiretroviral therapy (CD4 count, HIV RNA viral level) through a prospective, cross-sectional cohort study. Fifty-six HIV-infected patients who were already on, or who were started on PI-containing antiretroviral therapy were monitored for the development of dyslipidaemias. Therapy with PI-containing antiretroviral therapy was significantly associated with elevated serum triglyceride level (>250 mg/dl) (52% vs 8%, P=0.001). Patients with an adherence rate of at least 80% to a PI-containing regimen were significantly more likely to have elevated low density lipoprotein (LDL) cholesterol level as compared to patients with an adherence rate of <80% (79% vs 26%, P=0.03). Patients with an adherence rate of at least 80% to a PI-containing regimen were also significantly more likely to have severe hypertriglyceridaemia (>800 mg/dl) as compared to patients with an adherence rate of <80% (21% vs 4%, P=0.04). Viral load at the last study visit did not correlate with total cholesterol (r=-0.39, P=0.30), LDL cholesterol (r=0.57, P=0.30), or triglyceride level (r=0.55, P=0.20). However, there was a significant correlation between the last viral load and high density lipoprotein (HDL) cholesterol (r=0.79, P=0.035), i.e. lower viral load was associated with higher HDL cholesterol level. In conclusion, dyslipidaemia in patients with HIV infection was significantly associated with adherence to PI-containing antiretroviral therapy. Patients who are adherent to PI-containing regimens at least 80% of the time warrant close monitoring for the development of dyslipidaemia.

Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy.

BACKGROUND: Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. METHODS: A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. RESULTS: Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. CONCLUSION: Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.

Posttransplantation dialysis-associated infections: morbidity and impact on outcome in liver transplant recipients.

The aim of this study is to assess the predictors, impact on infectious morbidity, and outcome of posttransplantation dialysis in liver transplant recipients and to compare the results with data from patients who did not require dialysis after transplantation. The study sample included 176 consecutive patients undergoing liver transplantation; the median follow-up was 4.3 years. All patients were administered tacrolimus as primary immunosuppression. Overall, 16% (28 of 176 patients) of the patients required dialysis after transplantation. Patients requiring dialysis had significantly greater pretransplantation creatinine levels (2.4 v 1.2 mg/dL; P =.009), were more likely to require pretransplantation dialysis (21% v 1%; P =.0001), and had a greater rate of biopsy-proven rejection episodes (50%, 14 of 28 episodes v 20%, 30 of 148 episodes; P =.0009) and longer posttransplantation intensive care unit lengths of stay (P =.0001). The incidence of infections (91% v 41%; P =.0001) and episodes of infection per patient (2.4 v 0.7 episodes; P =.0001) were significantly greater in patients undergoing dialysis compared with those not undergoing dialysis. There was no difference in the frequency of cytomegalovirus (CMV) infection or disease; however, bacterial infections (87% v 31%; P =.0001) and invasive fungal infections (39% v 7%; P =.0001) were significantly more likely to occur in patients requiring dialysis. In logistic regression, dialysis (P =.0006) and CMV infection (P =.007) were independent significant predictors of major infections. Overall survival (assessed by Kaplan-Meier probability) was less in patients undergoing dialysis compared with those not undergoing dialysis (P =.0001). Among dialyzed patients, only 10% of those who survived had an invasive fungal infection compared with 46% of those who died (P =.08); 5 of 6 patients died within 1 month of the fungal infection. The need for dialysis portended a grave outcome in liver transplant recipients and identified a subgroup of patients at a significantly greater risk for major infections, particularly fungal infections, after liver transplantation.

Evolving trends in multiple-antibiotic-resistant bacteria in liver transplant recipients: a longitudinal study of antimicrobial susceptibility patterns.

The incidence, sources, impact on outcome, and temporal trends in multiple-antibiotic-resistant bacteria in liver transplant recipients over the last decade (from 1990 through 1999) were assessed. Of 165 consecutive patients who underwent transplantation, 31% (51 of 165 patients) had at least 1 infection caused by multiple-antibiotic-resistant bacteria. Overall, 69% (66 of 96 infections) of all bacterial infections were multiple-antibiotic resistant. Ninety-one percent (45 of 49 isolates) of the Staphylococcus aureus isolates, 50% (6 of 12 isolates) of the enterococci, and 54% of the gram-negative bacteria (47%; 7 of 15 Pseudomonas aeruginosa, and 60%; 12 of 20 Enterobacteriaceae) were multiple-antibiotic resistant. A significant trend toward an increase in infections caused by multiple-antibiotic-resistant bacteria (P =.003), largely caused by an increase in gram-positive infections, was documented through the decade. There was a significant increase in infections caused by methicillin-resistant S aureus (P =.0001) and vancomycin-resistant enterococci (P =.04) over time. The proportion of gram-negative isolates that were multiple-antibiotic resistant (P =.447) did not increase significantly over time. However, a strikingly high frequency of resistance to piperacillin or ceftazidime suggests that extended-spectrum beta-lactamase production in our Enterobacteriaceae may have been more prevalent than realized. Mortality at 1 year was significantly greater in patients with multiple-antibiotic resistant bacteria compared with all other patients (P =.001). These longitudinal trends have implications not only for guiding therapeutic practices, but ultimately for devising strategies to curtail multiple-antibiotic resistance in liver transplant recipients.

Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial.

BACKGROUND: The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary. METHODS: Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days. RESULTS: Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease. CONCLUSIONS: Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.

Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription.

Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS

Human herpesvirus-6 in liver transplant recipients: role in pathogenesis of fungal infections, neurologic complications, and outcome.

BACKGROUND: The clinical impact and relevance of human herpesvirus-6 (HHV-6) infection in liver transplant recipients, has not been fully discerned. METHODS: A prospective study of 80 consecutive liver transplant recipients was performed using surveillance cultures for HHV-6 at weeks 2, 3, 4, and 6 after transplantation. Viral isolation was used for the detection of HHV-6. RESULTS: HHV-6 infection occurred in 39% (31 of 80) of the patients. Patients with HHV-6 infection were more likely to have hepatocellular carcinoma as underlying liver disease (P=.09). Mental status changes of unidentifiable etiology were significantly more likely to occur in patients with HHV-6 compared with those without (26%, 9 of 31 vs. 6%, 3 of 49, P=.008). HHV-6 infection was an independent predictor of invasive fungal infections (odds ratio 8.3, 95% confidence interval, 1.2-58.0, P=.03). A significant association between HHV-6 infection and CMV infection after transplantation, CMV recipient and donor serostatus, rejection, or fever of unknown origin, could not be documented. Mortality at last follow-up in patients with HHV-6 infection (29%, 9 of 31) was significantly greater than those without HHV-6 (6%, 3 of 49, P=.008). CONCLUSIONS: Central nervous system complications of unknown etiology after liver transplantation may be related to HHV-6 infection. HHV-6 viremia was an independently significant predictor of invasive fungal infections and was associated with late mortality in liver transplantation recipients.

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

BACKGROUND: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. OBJECTIVE: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. DESIGN: Prospective, observational study. SETTING: HIV clinics in a Veterans Affairs medical center and a university medical center. PATIENTS: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). MEASUREMENTS: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). RESULTS: During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. CONCLUSIONS: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

Late-onset renal failure after liver transplantation: role of posttransplant alcohol use.

BACKGROUND: Late-onset renal failure is being increasingly recognized as a complication in patients undergoing liver transplantation for hepatitis C virus (HCV). However, its precise incidence, predisposing risk factors, and impact on outcome after liver transplantation, have not been defined. METHODS: The development of late-onset renal failure (defined as serum creatinine persistently >2.0 mg/dl, occurring more than 6 months posttransplant) was assessed in 120 consecutive liver transplant recipients who survived at least 6 months after transplantation. Fifty-seven percent (68/120) of the patients had undergone transplantation for liver disease due to HCV. The median follow-up was 5 years. RESULTS: Late-onset renal failure developed in 28% (33/120)of the patients. Posttransplant alcohol use (P=0.0001), posttransplant diabetes (P=0.0042), and recurrent HCV hepatitis (P=0.019) were significantly associated with late onset renal failure. In multivariate analysis, alcohol use (O.R. 10.7, 95%; CI 2.4-35.9, P=0.001) and diabetes (O.R. 2.1, 95%; CI 1.1-9.9, P=.03) were independently significant predictors of late onset renal failure. When only patients transplanted for HCV were analyzed, posttransplant alcohol use (P=0.004) was the only significant independent predictor of late-onset renal failure. HCV genotype 1b, as compared with other HCV genotypes, was associated with a higher rate of late-onset renal failure in patients with HCV; 70% of the patients with genotype 1b versus 32% of those with 1a and 33% of those with 2b, developed late onset renal failure (P=0.03). At a median follow up of 5 years, mortality in patients with HCV with late-onset renal failure was 52% as compared with 2% in those without renal failure (P=.0001). CONCLUSION: Late-onset renal failure in patients with HCV portended a grave outcome. Alcohol use was an independent predictor of late-onset renal failure in patients with HCV and represents a potentially modifiable risk factor for late-onset renal failure in these patients.

Methicillin-resistant Staphylococcus aureus: the other emerging resistant gram-positive coccus among liver transplant recipients.

We undertook a study of the characteristics and clinical impact of infections due to methicillin-resistant Staphylococcus aureus (MRSA) after liver transplantation. Of 165 patients who received liver transplants at our institution from 1990 through 1998, 38 (23%) developed MRSA infections. The predominant sources of infection were vascular catheters (39%; n=15), wound (18%; n=7), abdomen (18%; n=7), and lung (13%; n=5). A significant increase in MRSA infections (as a percentage of transplant patients infected per year) occurred over time (P=.0001). This increase was greater among intensive care unit patients (P=.001) than among nonintensive care unit hospital patients (P=.17). Cytomegalovirus seronegativity (P=.01) and primary cytomegalovirus infection were significantly associated with MRSA infections (P=.005). Thirty-day mortality among patients with MRSA infections was 21% (8/38). Mortality was 86% in patients with bacteremic MRSA pneumonia or abdominal infection and 6% in those with catheter-related bacteremia (P=.004). Thus the incidence of MRSA infection has increased exponentially among our liver transplant recipients since 1990. These infections have unique risk factors, time of onset, and a significant difference in site-specific mortality; deep-seated bacteremic infections, in particular, portend a grave outcome.