The shifting picture of HIV treatment, comorbidity and substance use among US MSM living with HIV.

OBJECTIVES: People living with HIV (PLWH) have increased risk of chronic disease and poor mental health. We aimed to explore HIV disease indicators, comorbidity, and risk behavior of recent antiretroviral therapy (ART) initiators to inform current needs of PLWH. METHODS: Men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS) who initiated ART between 2010 and 2018 (recent initiators) were compared with age-, race- and geographic location-matched men who initiated ART during 2000-2009 (early initiators). Measures of HIV disease, behavior, comorbidity and mental health were collected prospectively every 6 months using standardized forms. RESULTS: Recent initiators had higher current CD4 (median CD4 451 vs. 307 cells/µL, P < 0.0001) and nadir CD4 (451 vs. 300 cells/µL, P < 0.0001) than earlier initiators. The proportion achieving viral suppression within a year of starting ART was significantly higher in recent compared with earlier initiators (92% vs. 74%, P < 0.0001). Median [interquartile range (IQR)] time from HIV diagnosis to ART initiation was 5.4 (1.7-23.1) months in recent initiators. Comorbidity prevalence was high in recent initiators, including obesity (24%), hypertension (25%) and kidney disease (15%). Substance use continues to be common, including cigarette use (40%), daily alcohol use (88%) and marijuana use (46%). CONCLUSIONS: Improvements in getting individuals onto ART at an early stage have led to substantially higher CD4 cell counts at initiation. However, the high burden of comorbidity, substance use and poor mental health affecting MSM living with HIV in the US underscore ongoing challenges and our need to adapt and coordinate care.

Lymphopenia is associated with late onset Pneumocystis jirovecii pneumonia in solid organ transplantation.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) affected 5%-15% of solid organ transplant (SOT) recipients prior to universal prophylaxis, classically with trimethoprim-sulfamethoxazole (TMP-SMX). Guidelines generally recommend 6-12 months of prophylaxis post-SOT, yet optimal duration and robust PJP risk stratification have not been established. METHODS: A retrospective, single-center, case-control study of PJP among SOT recipients from January 1998 to December 2013 was conducted. Cases had positive PJ direct fluorescent antibody assay of respiratory specimens. Controls were matched 4:1 by nearest date of SOT. Univariate testing and multivariate logistic regressions were performed. RESULTS: Fifteen cases were identified among 5505 SOT recipients (0.27% rate) and analyzed vs 60 controls. PJP occurred on average 6.1 years (range 0.9-13.8) post-SOT; no case was receiving PJP prophylaxis at diagnosis. Most were treated with reduced immunosuppression and TMP-SMX plus steroids (80%). Six patients (40%) required critical care; 3 (20%) died. There were no significant demographic differences, though cases tended to be older at SOT (54 vs 48 years, P = .1). In univariate analysis, prior viral infection was more common among cases (67% vs 37%, P = .08). Lower absolute lymphocyte count (ALC) at diagnosis date was strongly associated with PJP (400 vs 1230 × 106  cells/µL, P < .001); odds of infection were high with ALC ≤ 500 × 106 cells (OR 18.7, P < .01). CONCLUSION: Pneumocystis jirovecii pneumonia is a rare, late complication of SOT with significant morbidity and mortality. Severe lymphopenia may be useful in identifying SOT recipients who warrant continued or reinstated PJP prophylaxis.

Ganciclovir-resistant cytomegalovirus infection in solid organ transplant recipients: a single-center retrospective cohort study.

BACKGROUND: Ganciclovir-resistant cytomegalovirus (GCV-R CMV) is an emerging challenge among solid organ transplant (SOT) recipients. The literature suggests that about 1% of abdominal transplant recipients develop GCV-R CMV infection. The epidemiology and outcome of GCV-R CMV in SOT recipients who have received alemtuzumab induction is not well described. METHODS: After Institutional Review Board approval, a single-center, retrospective review of 2148 abdominal SOT recipients between January 2006 and July 2011 at our institution (n = 2148) was conducted to identify patients with proven or empirically treated GCV-R CMV. Descriptive statistics on collected demographics, clinical course, and therapeutic outcomes were performed. RESULTS: Of 116 SOT recipient treated for CMV, 14 patients (12.1% of cases; 0.65% of all SOT patients) had proven or suspected GCV-R CMV. Eight (50%) developed GCV-R CMV while receiving valganciclovir (valGCV) prophylaxis. The remainder developed late-onset disease, after having completed an average 212 days (range 83-353) of prophylaxis. Resistance was clinically suspected an average of 103 days (range 10-455) after CMV infection was initially identified; 10 patients had confirmed genotypic resistance. Foscarnet therapy was associated with resolution of CMV in 13. CONCLUSION: Suboptimal dosing of valGCV is associated with development of GCV-R CMV. Our observed rate of GCV-R CMV in alemtuzumab-induced patients is similar to rates seen to historical data for other induction agents.

Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus.

Norovirus is a major cause of self-limited gastroenteritis worldwide. Prevention and treatment are thwarted by rapid viral evolution, and thus supportive care remains the mainstay of therapy. Chronic infection in immunocompromised hosts is increasingly described. We report a case of norovirus infection lasting 2543 days in a pancreas transplant recipient. Serial fecal specimens were obtained, from which a map of genetic relatedness was derived. The clinical course was complicated by renal failure that progressed to end-stage renal disease. Minimization of immunosuppression was associated with resolution of the infection. Subsequently, the patient experienced a suspected allograft rejection that did not compromise pancreas function. The patient later underwent living-related renal transplantation without recurrence of enteritis.

Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies.

BACKGROUND: The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management. METHODS: As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. RESULTS: All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. CONCLUSIONS: The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies.

BK virus replication and nephropathy after alemtuzumab-induced kidney transplantation.

BK virus nephropathy (BKVN) is a recognized cause of graft failure in kidney transplant recipients. There are limited data on the epidemiology of BK virus (BKV) infection after alemtuzumab induction. By clinical protocol, the kidney transplant recipients at our center were screened with BKV plasma PCR monthly for the first 4 months posttransplant then every 2-3 months for 2 years. A single center retrospective cohort study of all kidney transplant recipients from January 2008 to August 2010 was conducted to determine incidence and outcomes of BKV infection. Descriptive statistics and Kaplan-Meier analysis was performed. Of 666 recipients, 250 (37.5%) developed viruria, 80 (12%) developed viremia and 31 (4.7%) developed BKVN at a median of 17, 21 and 30 weeks, respectively. Induction with alemtuzumab did not significantly affect incidence of BKVN. Increased recipient age, African American race, acute graft rejection and CMV infection were significantly associated with the development of BKVN in multivariate analysis. The incidence of BK viruria, viremia and nephropathy was not significantly different among kidney transplant recipients who received alemtuzumab induction compared to patients receiving less potent induction.

Liver transplant outcomes in HIV+ haemophilic men.

Hepatitis C virus infection is the major cause of end-stage liver disease and the major indication for transplantation (OLTX), including among HIV-HCV co-infected individuals. The age of HCV acquisition differs between haemophilic and non-haemophilic candidates, which may affect liver disease outcomes. The purpose of the study was to compare rates of pre- and post-OLTX mortality between co-infected haemophilic and non-haemophilic subjects without hepatocellular cancer participating in the Solid Organ Transplantation in HIV Study (HIV-TR). Clinical variables included age, gender, race, liver disease aetiology, BMI, antiretroviral therapy, MELD score, CD4 + cell count, HIV RNA PCR and HCV RNA PCR. Time to transplant, rejection and death were determined. Of 104 HIV-HCV positive subjects enrolled, 34 (32.7%) underwent liver transplantation, including 7 of 15 (46.7%) haemophilic and 27 of 89 (30.3%) non-haemophilic candidates. Although haemophilic subjects were younger, median 41 vs. 47 years, P = 0.01, they were more likely than non-haemophilic subjects to die pre-OLTX, 5 (33.3%) vs. 13 (14.6%), P = 0.03, and reached MELD = 25 marginally faster, 0.01 vs. 0.7 years, P = 0.06. The groups did not differ in baseline BMI, CD4, detectable HIV RNA, detectable HCV RNA, time to post-OLTX death (P = 0.64), graft loss (P = 0.80), or treated rejection (P = 0.77). The rate of rejection was 14% vs. 36% at 1-year and 36% vs. 43% at 3-year, haemophilic vs. non-haemophilic subjects, respectively, and post-OLTX survival, 71% vs. 66% at 1-year and 38% vs. 53% at 3-year. Despite similar transplant outcomes, pretransplant mortality is higher among co-infected haemophilic than non-haemophilic candidates.

Use of the QuantiFERON-TB Gold interferon-gamma release assay for screening transplant candidates: a single-center retrospective study.

BACKGROUND: Tuberculosis (TB) reactivation is a rare but significant complication of organ transplantation, and screening of all transplant candidates for latent infection is recommended with either an interferon-γ release assay (IGRA) or tuberculin skin test (TST). METHODS: After institutional review board approval, we retrospectively collected data to describe the yield of transplant candidate screening using the QuantiFERON-TB Gold (QFT) and QuantiFERON-TB Gold In-Tube (QFT-IT) assays since the institution of TB screening in 2008 and the epidemiology of all cases of post-transplant TB in our institution since 2004. RESULTS: A total of 2392 patients were screened with either the QFT or QFT-IT assay through October 2009; 245 (10.2%) tested positive and 206 (8.6%) were indeterminate. Of those with positive results, 107 (43.7%) were foreign born and most of the remainder had prior TB exposures. Of the tests performed at a reference lab, 29% were indeterminate, whereas 14% were indeterminate using our in-house lab. The majority of indeterminate results were seen in liver transplant candidates (40.6% vs. 11.8% in non-liver candidates). Three of 694 (0.43%) screened patients who underwent transplantation developed TB post transplant. CONCLUSIONS: Post-transplant TB occurs at a low rate with universal IGRA-based candidate screening, which is comparable to studies using TST screening.

Carbapenem-resistant Acinetobacter baumannii infections after organ transplantation.

Multi-drug resistant (MDR) gram-negative infections among solid organ transplant (SOT) recipients have long been associated with high morbidity and mortality. Acinetobacter baumannii has emerged as a potent nosocomial pathogen with the recent acquisition of resistance to broad-spectrum beta-lactams, aminoglycosides, fluoroquinolones, and most notably, carbapenems. Despite a national rise in carbapenem-resistant A. baumannii (CRAB) infections, outcomes among SOT recipients with this emerging MDR pathogen are largely unknown. This single-center cohort is the first to describe the characteristics, complications, and outcomes among abdominal organ transplant recipients with CRAB. The current study suggests that SOT patients with CRAB suffer from prolonged hospitalization, infection with other MDR organisms, allograft dysfunction and loss, and high overall infection-related mortality.

Expanded infectious diseases screening program for Hispanic transplant candidates.

Most guidelines for pre-transplant screening recommend enhanced screening among patients with potential exposure to such pathogens as Strongyloides stercoralis and Trypanosoma cruzi, the cause of Chagas disease. The incidence of these diseases in the Hispanic immigrant population has not been extensively studied. Transplant candidates who were evaluated by our program's Hispanic Transplant Program were referred for expanded infectious disease screening including Mycobacterium tuberculosis, S. stercoralis, Leishmania, and T. cruzi. Between December 2006 and December 2008, 83 patients were screened. Most were from Mexico but we also screened patients from Ecuador, Puerto Rico, and Peru. Most patients lived in urban locations before moving to the United States. Latent tuberculosis infection (LTBI) was found in 20%, and 6.7% had serologic evidence of S. stercoralis infection. These patients underwent treatment of latent infection without difficulty. To date, 14 patients have undergone living-donor kidney transplantation. Two of these patients had positive Leishmania titers and are being followed clinically, 1 was treated for S. stercoralis, and 2 were treated for LTBI pre-transplant. All have done well without evidence of screened pathogens an average of 348 days (range 65-766 days) post transplant. Expanded screening identifies endemic infections in the Hispanic immigrant population that can be treated before transplant, thereby minimizing post-transplant infectious complications.

Cryptogenic liver disease in HIV-seropositive men.

OBJECTIVES: In the era of highly active antiretroviral therapy (HAART), liver disease has become a leading cause of morbidity and mortality in HIV-seropositive individuals. Although liver disease is commonly caused by viral co-infection, it has also been described in patients without viral hepatitis. In this study, we determined clinical factors associated with the development of cryptogenic liver disease in HIV-infected individuals. METHODS: HIV-seropositive and -seronegative patients undergoing evaluation for liver transplantation were selected if they met clinical criteria for cryptogenic liver disease. Clinical data were collected retrospectively, and radiological and histological data were reviewed separately. RESULTS: Nine HIV-seropositive individuals were compared with 41 HIV-seronegative patients with cryptogenic liver disease. Only one HIV-seropositive patient (11%) had cirrhosis, compared to 39 HIV-seronegative patients (93%) (P<0.001). Three HIV-infected patients (33%) had histological evidence of nodular regenerative hyperplasia. HIV-seropositive patients had significantly lower body mass indices, and lower Child-Pugh-Turcotte and Model for Endstage Liver Disease scores than HIV-seronegative patients (P<0.05). CONCLUSIONS: Advanced cryptogenic liver disease in HIV-infected patients is infrequently caused by cirrhosis, and more frequently by nodular regenerative hyperplasia. This disease entity may become more common in the HAART era, and may contribute to an increased morbidity in HIV-infected individuals.

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.

Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients.

Voriconazole, a new antifungal agent, is increasingly being used after HSCT. The hepatic cytochrome P450 isoenzyme 2C19 plays a significant role in voriconazole metabolism. As CYP2C19 exhibits significant genetic polymorphism, some patients metabolize voriconazole poorly resulting in increased plasma drug levels. The clinical significance of this is unknown, and the utility of monitoring voriconazole levels is unclear. Steady-state trough plasma voriconazole levels were obtained in 25 allogeneic HSCT recipients using an HPLC assay. Patients had drug levels checked once (n=13), twice (n=10), or > or =3 times (n=2) 5-18 days (median 10) after starting voriconazole or dose modification. The 41 voriconazole levels were 0.2-6.8 microg/ml (median 1.6); 6 (15%) were <0.5 (possibly below the in vitro MIC90 for Aspergillus spp.). Voriconazole concentrations correlated with aspartate aminotranferase (AST) (r=0.5; P=0.0009) and alkaline phosphatase (r=0.34; P=0.03), but not with creatinine, bilirubin and alanine aminotransferase (ALT). Since liver dysfunction is common after HSCT, it was not possible to determine if elevated AST and alkaline phosphatase levels were the cause or the consequence of higher voriconazole levels. We conclude that trough voriconazole levels vary considerably between patients, and suggest monitoring levels in patients receiving voriconazole for confirmed fungal infections, and in those with elevated AST or alkaline phosphatase levels.

Enterococcus faecium bacteremia: does vancomycin resistance make a difference?

BACKGROUND: Enterococcus faecium has received increased attention, primarily due to the emergence of vancomycin resistance. The purpose of this investigation was to study the epidemiological characteristics of vancomycin-resistant E faecium (VRE) bacteremia and to determine the clinical impact of vancomycin resistance on the outcome of patients with this infection. METHODS: We retrospectively analyzed the clinical features and outcome of 53 patients with E faecium bacteremia. RESULTS: From January 1992 until December 1995, there were 32 episodes of bacteremia caused by vancomycin-susceptible E faecium (VSE) and 21 caused by VRE. An intra-abdominal site was the most common source of bacteremia in both groups. All of the VRE and 78% of VSE bacteremia cases were nosocomially acquired. Previous administration of vancomycin was associated with VRE bacteremia (P<.001), as were indwelling bladder catheters (P=.01). Fifty-nine percent of the patients with VSE bacteremia survived vs 24% with VRE (P=.009), despite similar severity-of-illness scores. In 62% of the patients with VRE sepsis, death was related to the bacteremia (P=.01). Patients infected with VRE had longer hospitalizations than those with VSE (34.8 vs 16.7 days, respectively) (P=.004), were more likely to be on the medical service (P=.03), and on the average, had hospitalization costs of more than $27,000 per episode than did patients with VSE bloodstream infection ($83,897 vs $56,707, respectively) (P=.04). CONCLUSIONS: Vancomycin-resistant E faecium bacteremia is a complication of prolonged hospitalization in debilitated patients. Vancomycin resistance has a negative impact on survival in patients with E faecium bacteremia and leads to higher health care costs.

Detection of vancomycin-resistant enterococci before and after antimicrobial therapy: use of conventional culture and polymerase chain reaction.

Antimicrobial therapy can increase the colonization density of gastrointestinal vancomycin-resistant enterococci (VRE). Among previously VRE-colonized patients, we evaluated VRE colonization before and after initiation of antimicrobial therapy by means of polymerase chain reaction (PCR) and culture. Perianal swab samples were obtained at admission to the hospital and after receipt of antimicrobial therapy. At admission, 12 (21%) of 56 patients were culture positive, and 17 (30%) had vanA or vanB genes detected by PCR. Culture results showed that 25 (86%) of 29 culture-negative patients from whom a second swab sample was obtained remained culture negative, 2 (6.9%) had a relapse of colonization with a strain related to the previously colonizing strain type (2 and 6 days after admission), and 2 (6.9%) tested positive for a previously undetected strain type (16 and 19 days after admission). PCR at admission detected VRE in 1 of the 2 patients who later relapsed. Patients with negative results of culture of the initial swab sample and of PCR were unlikely to relapse after receipt of antimicrobial therapy.

Recovery of vancomycin-resistant enterococci on fingertips and environmental surfaces.

OBJECTIVE: To determine the recovery of vancomycin-resistant enterococci (VRE) on fingertips, gloved fingertips, and environmental surfaces commonly encountered in the healthcare setting, and to examine the importance of handwashing on the removal of these organisms. DESIGN: Two clinical isolates of VRE (Enterococcus faecalis and Enterococcus faecium) were inoculated onto the hands of healthy human volunteers and the following environmental surfaces: countertops, bedrails, telephones, and stethoscopes. Following inoculation, samples were obtained at various time intervals to determine rates of recovery of organisms. To evaluate the effects of handwashing on enterococcal recovery, two different soap preparations were tested. Hands were washed with water alone or with one of the soaps and water. The soap and water studies were performed with a 5-second and a 30-second wash. RESULTS: Both enterococcal strains survived for at least 60 minutes on gloved and ungloved fingertips. The E faecalis was recoverable from countertops for 5 days; the E faecium persisted for 7 days. For bedrails, both enterococcal species survived for 24 hours without significant reduction in colony counts. The bacteria persisted for 60 minutes on the telephone handpiece and for 30 minutes on the diaphragmatic surface of the stethoscope. A 5-second wash with water alone resulted in virtually no change in recovery of enterococci; a 30-second wash with water plus either soap was necessary to eradicate the bacteria from hands completely. CONCLUSION: VRE are capable of prolonged survival on hands, gloves, and environmental surfaces. Hands should be washed thoroughly and gloves removed following contact with patients infected or colonized with these multidrug-resistant bacteria. Finally, environmental surfaces may serve as potential reservoirs for nosocomial transmission of VRE and need to be considered when formulating institutional infection control policies.

Molecular epidemiology of vancomycin-resistant enterococci: a 2-year perspective.

OBJECTIVE: To determine the molecular epidemiology of vancomycin-resistant enterococci (VRE) at our medical center in order to identify the extent of strain clonality and possible transmission patterns of this pathogen. DESIGN: An important facet of our infection control program includes molecular typing of all clinical and surveillance isolates of VRE to determine transmission patterns in the hospital. Molecular strain typing is performed by restriction endonuclease analysis (REA) of genomic DNA. REA patterns are visually compared to categorize VRE strains into type and subtype designations. SETTING: A 588-bed, university-affiliated, tertiary-care hospital and a neighboring 155-bed rehabilitation facility. RESULTS: From January 1995 through December 1996, 379 VRE isolates were collected from 197 patients. Thirty-three genotypes were determined by REA typing; 15 genotypes were implicated in 29 instances of potential nosocomial transmission. Three major clusters of VRE involving patients on multiple nursing units and two adjacent hospitals were identified. The remaining instances of nosocomial transmission occurred in small patient clusters. CONCLUSIONS: In conclusion, the VRE epidemic at this medical center is polyclonal. VRE transmission patterns are complex, and, while large clusters do occur, the usual pattern of nosocomial acquisition of this pathogen occurs in the setting of "mini-clusters".

Molecular typing for investigating an outbreak of Candida krusei.

Invasive infections due to Candida krusei are often observed in immunocompromised patients who have received prior therapy with fluconazole, although infection has also occurred in patients in the absence of this antifungal agent. From August 25 through September 19, 1995, we identified four patients with C. krusei fungemia on our hematology/oncology unit. Molecular typing of all the isolates was performed by restriction endonuclease analysis of genomic DNA using HinfI. A total of 7 patients found to be colonized or infected with C. krusei were matched with 14 controls. There was no difference between the cases and controls with respect to underlying disease, duration of hospitalization, or neutropenia. The numbers of days of hyperalimentation, corticosteroids, and antibiotics were similar between both groups. The mean number of antibiotics was greater in the cases versus controls (5.0 versus 2.5; p = .003). There was no difference with respect to total dose or duration of fluconazole administration. Molecular typing of the isolates revealed that four had identical DNA banding patterns, plus another two that differed by one band and were considered related. Three historical strains were unrelated. In conclusion, this report demonstrates that molecular typing can be used to define clonality and, thereby, support increased infection control practices to eliminate such outbreaks when evidence of clonal spread is present.

Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin: a phenotypic assessment of NCCLS guidelines.

Between December 1, 1993, and December 1, 1996, we tested 4,411 isolates of Enterococcus sp. at gentamicin concentrations of 500 micrograms/mL and 2000 micrograms/mL using agar dilution to phenotypically categorize them into 3 groups: those with a MIC < or = 500 micrograms/mL (n = 3,132; 71%); a MIC > 500, but < or = 2000 micrograms/mL (n = 441; 10%); and those with a MIC > 2000 micrograms/mL (n = 838; 19%). Ten unique strains of each phenotype were tested to determine which gentamicin concentration was the best in vitro predictor of synergy with ampicillin. Testing was done by a time-kill method using clinically achievable levels of ampicillin and gentamicin. We found that for the gentamicin MIC < or = 500 micrograms/mL group, 7 of 10 isolates demonstrated synergy with ampicillin as manifested by a > or = 2 log10 increase in killing versus the effect of ampicillin alone (at 1/2 the MIC for ampicillin). In the group sensitive to a gentamicin MIC range between > 500 and < or = 2,000 micrograms/mL, none of the 10 isolates demonstrated synergy. Absence of synergy was also found in the group resistant to 2,000 micrograms/mL of gentamicin. Assessment of eight additional enterococcal isolates with reduced sensitivity to ampicillin (MIC from 32-256 micrograms/mL) found no correlation between gentamicin sensitivity at 500 micrograms/mL and any in vitro test for synergy, nor with clinical therapeutic outcome. Gentamicin at 2 micrograms/mL combined with ampicillin was as effective in enhancing killing as a higher level of 4 micrograms/mL. These findings validate the current NCCLS guideline for predicting synergistic activity against enterococci in strains with usual susceptibility to ampicillin, and suggest that a therapeutic level less than maximal recommended dosing is sufficient when using gentamicin in this setting.

Therapeutic options for HIV-associated bodyweight loss. A risk-benefit analysis.

Involuntary bodyweight loss, a common complication of infection with HIV, is an indicator of poor prognosis and decreased survival. Because of the multifactorial pathogenesis of HIV-related wasting, emerging therapies are directed at the multiple proposed mechanisms of involuntary bodyweight loss. The initial evaluation and treatment of HIV-related bodyweight loss is focused on the identification and treatment of reversible causes of bodyweight loss, such as secondary opportunistic infections or endocrine dysfunction. Nutritional intervention should begin in the early stages of HIV infection and continue throughout the life of the patient. Of the appetite stimulants, megestrol most consistently promotes bodyweight gain, but with a predominance of fat, not lean, body mass. Anabolic therapies such as testosterone derivatives and recombinant human growth hormone (somatropin) stimulate the addition of lean body mass and are begin actively researched for the treatment of HIV-associated wasting. Finally, thalidomide, a potent inhibitor of tumour necrosis factor-alpha, is a potentially useful therapy that is still under investigation. New research into the treatment of HIV-related bodyweight loss is focusing on combination therapies.