MANAGEMENT OF ENDOCRINE DISEASE: Cardiovascular risk assessment, thromboembolism, and infection prevention in Cushing's syndrome: a practical approach.

Cushing's syndrome (CS) is associated with increased mortality that is driven by cardiovascular, thromboembolic, and infection complications. Although these events are expected to decrease during disease remission, incidence often transiently increases postoperatively and is not completely normalized in the long-term. It is important to diagnose and treat cardiovascular, thromboembolic, and infection complications concomitantly with CS treatment. Management of hyperglycemia/diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with clinical care standards. Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism, and treatment adjustments can be made based on disease pathophysiology and drug-drug interactions. Thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding. Pneumocystis jiroveci pneumonia prophylaxis should be considered for patients with high urinary free cortisol at the initiation of hypercortisolism treatment.

Diagnosing Pneumocystis jirovecii pneumonia: A review of current methods and novel approaches.

Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization of the life-forms in bronchoalveolar lavage fluid. This method has proven insensitive, and invasive procedures may be needed to obtain adequate samples. Molecular methods of detection such as polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and antibody-antigen assays have been developed in an effort to solve these problems. These techniques are very sensitive and have the potential to detect Pneumocystis life-forms in noninvasive samples such as sputum, oral washes, nasopharyngeal aspirates, and serum. This review evaluates 100 studies that compare use of various diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) in patient samples. Novel diagnostic methods have been widely used in the research setting but have faced barriers to clinical implementation including: interpretation of low fungal burdens, standardization of techniques, integration into resource-poor settings, poor understanding of the impact of host factors, geographic variations in the organism, heterogeneity of studies, and limited clinician recognition of PCP. Addressing these barriers will require identification of phenotypes that progress to PCP and diagnostic cut-offs for colonization, generation of life-form specific markers, comparison of commercial PCR assays, investigation of cost-effective point of care options, evaluation of host factors such as HIV status that may impact diagnosis, and identification of markers of genetic diversity that may be useful in diagnostic panels. Performing high-quality studies and educating physicians will be crucial to improve the rates of diagnosis of PCP and ultimately to improve patient outcomes.

Estimating the burden of invasive and serious fungal disease in the United Kingdom.

BACKGROUND: The burden of fungal disease in the UK is unknown. Only limited data are systematically collected. We have estimated the annual burden of invasive and serious fungal disease. METHODS: We used several estimation approaches. We searched and assessed published estimates of incidence, prevalence or burden of specific conditions in various high risk groups. Studies with adequate internal and external validity allowed extrapolation to estimate current UK burden. For conditions without adequate published estimates, we sought expert advice. RESULTS: The UK population in 2011 was 63,182,000 with 18% aged under 15 and 16% over 65. The following annual burden estimates were calculated: invasive candidiasis 5142; Candida peritonitis complicating chronic ambulatory peritoneal dialysis 88; Pneumocystis pneumonia 207-587 cases, invasive aspergillosis (IA), excluding critical care patients 2901-2912, and IA in critical care patients 387-1345 patients, <100 cryptococcal meningitis cases. We estimated 178,000 (50,000-250,000) allergic bronchopulmonary aspergillosis cases in people with asthma, and 873 adults and 278 children with cystic fibrosis. Chronic pulmonary aspergillosis is estimated to affect 3600 patients, based on burden estimates post tuberculosis and in sarcoidosis. CONCLUSIONS: Uncertainty is intrinsic to most burden estimates due to diagnostic limitations, lack of national surveillance systems, few published studies and methodological limitations. The largest uncertainty surrounds IA in critical care patients. Further research is needed to produce a more robust estimate of total burden.

Grouped Cases of Pulmonary Pneumocystosis After Solid Organ Transplantation: Advantages of Coordination by an Infectious Diseases Unit for Overall Management and Epidemiological Monitoring.

OBJECTIVE To determine the origin of grouped cases of Pneumocystis pneumonia in solid-organ transplant recipients at our institution. DESIGN A case series with clinical examinations, genotyping, and an epidemiological survey. SETTING A university hospital in France. PATIENTS We report 12 solid-organ transplant recipients with successive cases of Pneumocystis pneumonia that occurred over 3 years; 10 of these cases occurred in a single year. METHODS We used molecular typing of P. jirovecii strains by multilocus sequence typing and clinical epidemiological survey to determine potential dates and places of transmission. RESULTS Between May 2014 and March 2015, 10 solid-organ transplant recipients (5 kidney transplants, 4 heart transplants, and 1 lung transplant) presented with Pneumocystis pneumonia. Molecular genotyping revealed the same P. jirovecii strain in at least 6 patients. This Pneumocystis strain was not identified in control patients (ie, nontransplant patients presenting with pulmonary pneumocystosis) during this period. The epidemiological survey guided by sequencing results provided information on the probable or possible dates and places of contamination for 5 of these patients. The mobile infectious diseases unit played a coordination role in the clinical management (adaptation of the local guidelines) and epidemiological survey. CONCLUSION Our cardiac and kidney transplant units experienced grouped cases of pulmonary pneumocystosis. Genotyping and epidemiological surveying results suggested interhuman contamination, which was quickly eliminated thanks to multidisciplinary coordination. Infect Control Hosp Epidemiol 2017;38:179-185.

Burden of serious fungal infections in Belgium.

We aimed to estimate the total number of serious fungal infections occurring yearly in Belgium. The number of cryptococcal infections was retrieved from the National Reference Center for Mycosis. Populations at risk and fungal infections frequencies in these populations were used to estimate incidence or prevalence of other fungal infections. The Belgian population consists of 11.10 million people. Cryptococcal meningitis is rare. In all, 15 of the 1227 newly diagnosed HIV/AIDS cases presented with Pneumocystis jirovecii pneumonia. This accounts for ±14% of total PCP cases (n = 120). The incidence of candidaemia is estimated as 5/100,000 resulting in 555 cases and 213 deaths. A total number of 675 invasive aspergillosis cases and ≥169 deaths attributed to this infection were calculated. Chronic pulmonary aspergillosis is estimated to be prevalent in 662 cases. Allergic bronchopulmonary aspergillosis cases were estimated to be 23,119 applying a 2.5% and 15% rate in adult asthma and cystic fibrosis patients respectively. Severe asthma with fungal sensitisation cases was estimated to be 30,402. There were 174,760 women with recurrent Candida vaginitis assuming a 6% rate in women aged between 15 and 50. Approximately 233,000 people of the Belgian population (2.1%) are estimated to suffer from a fungal infection on a yearly basis.

Burden of serious fungal infections in the Czech Republic.

We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care.

Burden of serious fungal infections in Nepal.

There are few reports of serious fungal infections in Nepal though the pathogenic and allergenic fungi including Aspergillus species are common in the atmosphere. Herein, we estimate the burden of serious fungal infections in Nepal. All published papers reporting fungal infection rates from Nepal were identified. When few data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Of the 27.3 M population, about 1.87% was estimated to suffer from serious fungal infections annually. We estimated the incidence of fungal keratitis at 73 per 100,000 annually. Chronic obstructive pulmonary disease is common with 215,765 cases, contributing to 1119 cases of invasive aspergillosis annually. Of 381,822 adult asthma cases, we estimated 9546 patients (range 2673-13,364) develop allergic bronchopulmonary aspergillosis and 12,600 have severe asthma with fungal sensitisation. Based on 26,219 cases of pulmonary tuberculosis, the annual incidence of new chronic pulmonary aspergillosis (CPA) cases was estimated at 1678 with a 5 year period prevalence of 5289, 80% of CPA cases. Of 22,994 HIV patients with CD4 counts <350 not on antiretrovirals, Pneumocystis pneumonia was estimated at 990 cases annually. Cases of oral and oesophageal candidiasis in HIV/AIDS patients were estimated at 10,347 and 2950, respectively. There is a significant burden of serious fungal infections in Nepal. Epidemiological studies are necessary to validate these estimates.

Burden of fungal infections in Qatar.

Few estimates of fungal disease frequency have been attempted in the Middle East. We have estimated the burden of fungal infections in Qatar. The aim of the study was to compute and determine the burden of serious fungal infections, in an attempt to estimate fungal disease frequency, which has not previously been attempted in this country. Disease statistics were collected from the Microbiology laboratory database and from 2011 WHO statistics. The data are expressed per 100,000 populations. The reported cases of candidaemia rose to 288 with an estimated rate of 15.4/100,000. A real increase in the burden of candidaemia was found over that previously reported (12.9/100,000) for the years 2004-2009. Candida peritonitis was estimated in 8.02 cases/100,000 population. Recurrent (≥4 year(-1) ) vaginal infections affect at least 32,782 women with a rate of 3506/100,000 inhabitants. Severe asthma with fungal sensitisation affected 1486 people, allergic bronchopulmonary aspergillosis 1126 people and chronic pulmonary aspergillosis 176 people. Rhinosinusitis, mucormycosis and Fusarium infection occurred at rates of 2.31, 1.23, 1.86 cases/100,000 respectively. The estimated rate of invasive aspergillosis was very low (0.6/100,000). Low rates of Cryptococcus meningitis and Pneumocystis pneumonia are attributable to low HIV infection rates. In conclusion, fungal infections are increasingly reported, especially candidaemia. Surveillance and guidelines are needed to optimise care and management of common fungal infections. In addition, a fungal registry system needs development for surveillance.

The burden of serious fungal diseases in Russia.

The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082.

Burden of serious fungal infections in Tanzania.

The incidence and prevalence of fungal infections in Tanzania remains unknown. We assessed the annual burden in the general population and among populations at risk. Data were extracted from 2012 reports of the Tanzanian AIDS program, WHO, reports, Tanzanian census, and from a comprehensive PubMed search. We used modelling and HIV data to estimate the burdens of Pneumocystis jirovecii pneumonia (PCP), cryptococcal meningitis (CM) and candidiasis. Asthma, chronic obstructive pulmonary disease and tuberculosis data were used to estimate the burden of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Burdens of candidaemia and Candida peritonitis were derived from critical care and/or cancer patients' data. In 2012, Tanzania's population was 43.6 million (mainland) with 1,500,000 people reported to be HIV-infected. Estimated burden of fungal infections was: 4412 CM, 9600 PCP, 81,051 and 88,509 oral and oesophageal candidiasis cases respectively. There were 10,437 estimated post-tuberculosis CPA cases, whereas candidaemia and Candida peritonitis cases were 2181 and 327 respectively. No reliable data exist on blastomycosis, mucormycosis or fungal keratitis. Over 3% of Tanzanians suffer from serious fungal infections annually, mostly related to HIV. Cryptococcosis and PCP are major causes of mycoses-related deaths. National surveillance of fungal infections is urgently needed.

Burden of serious fungal infections in Ukraine.

Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually.

Estimating the burden of fungal disease in Vietnam.

Data regarding the prevalence of fungal infections in Vietnam are limited yet they are likely to occur more frequently as increasingly sophisticated healthcare creates more iatrogenic risk factors. In this study, we sought to estimate baseline incidence and prevalence of selected serious fungal infections for the year 2012. We made estimates with a previously described actuarial method, using reports on the incidence and prevalence of various established risk factors for fungal infections from Vietnam, or similar environments, supplemented by personal communications. Global data were used if local data were unavailable. We estimated 2,352,748 episodes of serious fungal infection occurred in Vietnam in 2012. Frequent conditions included recurrent vaginal candidiasis (3893/100,000 women annually), tinea capitis (457/100,000 annually) and chronic pulmonary aspergillosis (61/100,000/5 year period). We estimated 140 cases of cryptococcal meningitis, 206 of penicilliosis and 608 of Pneumocystis jirovecii pneumonia. This is the first summary of Vietnamese fungal infections. The majority of severe disease is due to Aspergillus species, driven by the high prevalence of pulmonary tuberculosis. The AIDS epidemic highlights opportunistic infections, such as penicilliosis and cryptococcosis, which may complicate immunosuppressive treatments. These estimates provide a useful indication of disease prevalence to inform future research and resource allocation but should be verified by further epidemiological approaches.

Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an important infection-related complication, whose mode of transmission remains uncertain. METHODS: We investigated a nosocomial cluster of 14 PJP cases (11 confirmed and 3 probable) in kidney transplant recipients using epidemiological and genotyping methods. RESULTS: Poisson regression calculated an incidence density ratio of 42.8 (95% confidence interval [CI], 14.1-129.3) versus background 0.64 cases of 1000 patient-years (P<0.001). All patients presented with respiratory failure, 10 required ventilation, two died, and six transplants failed, costing $31,854 (±SD $26,048) per patient. Four-locus multilocus sequence typing analysis using DNA extracts from 11 confirmed cases identified two closely related genotypes, with 9 of 11 sharing an identical composite multilocus sequence typing genotype. Contact tracing found colocalization of cases within clinic waiting areas, suggesting person-to-person transmission. Minimal and maximal PJP incubation periods were 124±83 to 172±71 days, respectively. Oropharyngeal washes from outpatient staff and ambient air samples were negative for P. jirovecii DNA. Cohort analysis (14 cases vs. 324 unaffected clinic control patients) identified independent risk factors including previous cytomegalovirus infection (odds ratio [OR], 65.9; 95% CI, 7.9-550; P<0.001), underlying pulmonary disease (OR, 10.1; 95% CI, 2.3-45.0; P=0.002), and transplant dysfunction (OR=1.61 per 10 mL/min/1.73 m, 95% CI, 1.15-2.25, P=0.006). The outbreak was controlled by reintroduction of trimethoprim/sulfamethoxazole prophylaxis to all potentially exposed clinic patients and its extension to 12 months in recent recipients. CONCLUSIONS: Nosocomial PJP clusters are likely due to interhuman transmission by airborne droplets to susceptible hosts. Prompt recognition and a strategy of early preemptive blanket PJP prophylaxis to all exposed transplant clinic recipients from the third confirmed case are recommended to limit outbreak escalation.

Cost-effectiveness analysis of diagnostic options for pneumocystis pneumonia (PCP).

BACKGROUND: Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented. METHODS AND FINDINGS: We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options. CONCLUSIONS: For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.

Critical illness in HIV-infected patients in the era of combination antiretroviral therapy.

As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non-AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research.

High rates of primary Mycobacterium avium complex and Pneumocystis jiroveci prophylaxis in the United States.

BACKGROUND: National data from the mid-1990s demonstrated that many eligible patients with HIV infection do not receive prophylaxis for opportunistic infections (OIs) and that racial and gender disparities existed in OI prophylaxis receipt. OBJECTIVE: We examined whether demographic disparities in use of OI prophylaxis persist in 2001 and if outpatient care is associated with OI prophylaxis utilization. RESEARCH DESIGN: Demographic, clinical, and pharmacy utilization data were collected from 10 U.S. HIV primary care sites in the HIV Research Network. SUBJECTS: This study consisted of adult patients (>or=18 years old) in longitudinal HIV primary care. MEASURES: Indications for Pneumocystis jiroveci pneumonia (PCP) or Mycobacterium avium complex (MAC) prophylaxis were 2 or more CD4 counts less than 200 or 50 cells/mm(3) during calendar year (CY) 2001, respectively. Using multivariate logistic regression, we examined demographic and clinical characteristics associated with receipt of PCP or MAC prophylaxis and the association of outpatient utilization with appropriate OI prophylaxis. RESULTS: Among eligible patients, 88.1% received PCP prophylaxis and 87.6% received MAC prophylaxis. Approximately 80% had 4 or more outpatient visits during CY 2001. Adjusting for care site, male gender (odds ratio [OR], 1.47), Medicare coverage (OR, 1.60), and having 4 or more outpatient visits in a year (OR, 2.34) were significantly associated with increased likelihood of PCP prophylaxis. Adjusting for care site, having 4 or more outpatient visits in a year (OR, 1.85) was associated with increased likelihood of receipt of MAC prophylaxis. There were no demographic or insurance characteristics associated with receipt of MAC prophylaxis. CONCLUSIONS: The overall prevalence of OI prophylaxis has increased since the mid-1990s, and previous racial and HIV risk factor disparities in receipt of OI prophylaxis have waned. Integration into the healthcare system is an important correlate of receiving OI prophylaxis.

Analysis of a population-based Pneumocystis carinii pneumonia index as an outcome measure of access and quality of care for the treatment of HIV disease.

OBJECTIVES: A population-based Pneumocystis carinii pneumonia (PCP) Index was developed in New York City to identify geographic areas and subpopulations at increased risk for PCP. METHODS: A zip code-level PCP Index was created from AIDS surveillance and hospital discharge records and defined as (number of PCP-related hospitalizations)/(number of persons living with AIDS). RESULTS: In 1997, there were 2262 hospitalizations for PCP among 39 740 persons living with AIDS in New York City (PCP Index =.05691). PCP Index values varied widely across neighborhoods with high AIDS prevalence (West Village =.02532 vs Central Harlem =.08696). Some neighborhoods with moderate AIDS prevalence had strikingly high rates (Staten Island =.14035; northern Manhattan =.08756). CONCLUSIONS: The PCP Index highlights communities in particular need of public health interventions to improve HIV-related service delivery.

Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued?

Solid organ transplant recipients are at risk for Pneumocystis carinii pneumonia (PCP), but the risk of PCP beyond 1 year is poorly defined. We identified 25 cases of PCP in 1,299 patients undergoing solid organ transplantation between 1987 and 1996 at The Cleveland Clinic Foundation (4.8 cases per 1,000 person transplant-years [PTY]). Ten (36%) of 28 PCP cases (transplantation was performed before 1987 in three cases) occurred > or = 1 year after transplantation, and no patient developed PCP while receiving prophylaxis for PCP. The incidence of PCP during the first year following transplantation was eight times higher than that during subsequent years. The highest rate occurred among lung transplant recipients (22 cases per 1,000 PTY), for whom the incidence did not decline beyond the first year of transplantation. We conclude that the incidence of PCP is highest during the first year after transplantation and differs by type of solid organ transplant. Extending the duration of PCP prophylaxis beyond 1 year may be warranted for lung transplant recipients.

Experience with a managed care approach to HIV infection: effectiveness of an interdisciplinary team.

To evaluate the function and effectiveness of a multidisciplinary team for managing human immunodeficiency virus (HIV) infection, we conducted a follow-up cohort study of HIV-positive patients managed according to a clinical care path at a staff-based health maintenance organization (HMO). The study group consisted of 230 HIV-positive health plan members who received care at the Kaiser Permanente Santa Rosa medical center (KPMC-SRO). In 1994, the comparison group consisted of 4747 HIV-positive health plan members who received care at Kaiser Permanente's 18 other medical centers in northern California. The percentages of acquired immunodeficiency syndrome (AIDS) and HIV-positive patients as determined by CD4+ T-cell counts were similar (P = 0.97). Compared with patients at the other Kaiser Permanente medical centers, KPMC-SRO patients had more visits with nurse practitioners (rate ratio [RR] = 1.72) and nutritionists (RR = 12.3) and fewer visits with primary care physicians (RR = 0.82). More HIV-positive members at KPMC-SRO received social workers' services (27% at KPMC-SRO vs 6% for patients at the other Kaiser Permanente medical centers) and fewer used emergency services (RR = 0.92) and psychiatric services (RR = .89). At KPMC-SRO, the mean number of days that AIDS patients spent in the hospital decreased from 7.8 (1991) to 2.01 (1994). Hospital admissions were fewer (AIDS patients, RR = 0.67; HIV-positive patients without AIDS, RR = 0.45), and length of stay was briefer, compared with patients at the other Kaiser Permanente Medical Centers. The mean cost of HIV-related drugs for patients seen at KPMC-SRO ($2343 per infected member) was lower than that for patients seen elsewhere in the region ($3289 per infected member). These results suggest that in an HMO setting, managed care provided by a dedicated interdisciplinary team according to a clinical care path can substantially and favorably affect resource use.