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Objective: To determine if a general dentist with human immunodeficiency virus (HIV) infection transmitted HIV to any of his patients.Design: A cohort study in which all patients treated by a dentist who developed the acquired immunodeficiency syndrome (AIDS) were identified and attempts were made to contact all patients for HIV antibody testing.Setting: A general dentistry clinic operated by the Department of Veterans Affairs in southeastern Florida.Participants: All patients treated by a dentist during the 5 3/4 years before he developed AIDS were identified in a computerized registry of dental care.Main Outcome Measures: Attempts were made to contact all living patients for counseling and HIV antibody testing. Living patients with newly identified HIV infection were interviewed, and DNA sequence analysis was performed to compare genetic relatedness of their HIV to that of the dentist. Death certificates were obtained for decreased patients, and the medical records of those with diagnoses suggestive of HIV disease or drug abuse and those dying under the age of 50 years were reviewed in detail.Results: There were 1192 patients who had undergone 9267 procedures, of whom 124 were deceased. A review of the death certificates of the deceased patients identified five who had died with HIV infection, all of whom were either homosexuals or users of illicit intravenous drugs. We were able to locate 962 (92%) of the remaining 1048 patients, and 900 agreed to be tested. Infection with HIV was documented in five of the 900 patients, including four who had clear evidence of risk factors for acquiring HIV infection. One patient who had only a single evaluation by the dentist denied high-risk behavior. Comparative DNA sequence analysis demonstrated that the viruses from the dentist and these five patients were not closely related.Conclusion: This study indicates that the risk for transmission of HIV from a general dentist to his patients is minimal in a setting in which universal precautions are strictly observed. Programs to ensure compliance with universal precautions would appear preferable to programs for widespread testing of dentists. [ABSTRACT FROM AUTHOR]

BACKGROUND: While strategies for medical care for human immunodeficiency virus-related Pneumocystis carinii pneumonia (PCP) are well established, racial variations in care have not been evaluated. OBJECTIVE: To determine whether sociodemographic characteristics influence patterns of care and patient outcomes, by analyzing the use of diagnostic tests and anti-PCP medications and in-hospital mortality rates for persons who were hospitalized with human immunodeficiency virus-related PCP. METHODS: Retrospective chart review of a cohort of 627 Veterans Administration (VA) patients and 1547 non-VA patients with empirically treated or cytologically confirmed PCP who were hospitalized from 1987 to 1990. Outcomes included representative aspects of the process of care for PCP and short-term mortality rates. RESULTS: Among VA patients, black and Hispanic patients were not significantly different from white patients with regard to in-hospital mortality rates, use and timing of a bronchoscopy, or receipt of timely anti-PCP medications. Among non-VA patients, black and Hispanic patients were more likely to die in the hospital and less likely to undergo a diagnostic bronchoscopy in the first 2 days of hospitalization. These racial and ethnic group differences in the use of a bronchoscopy and in-hospital mortality among non-VA patients were almost fully accounted for by differences in health insurance status and hospital characteristics. CONCLUSIONS: Racial factors do not appear to be an important determinant of the intensity of diagnostic or therapeutic care among patients who are hospitalized with PCP. Variations in care are largely attributable to differences in health insurance and admitting hospital characteristics. [ABSTRACT FROM AUTHOR]

Prophylaxis is as routine as a visit to the dentist -- yet in many cases its efficacy has not been documented. With the rising costs of drugs and the emergence of resistant organisms, it's time to update the guidelines. [ABSTRACT FROM AUTHOR]

Hypothermia-related deaths affect vulnerable populations and are preventable. They account for the vast majority of weather-related deaths in the United States. The postmortem diagnosis of hypothermia can be challenging, as there are no pathognomonic signs. The electronic databases of the New York City Office of Chief Medical Examiner and Harris County Institute of Forensic Sciences were searched for all fatalities where the primary cause of death included hypothermia, between January 2009 and July 2019. There were 139 hypothermia deaths in New York City (NYC) with an average annualized rate of 1.7 per million. During this same time, there were 50 hypothermia deaths in Houston with an average annualized rate of 2.4 per million. Males were more likely to die of hypothermia compared to females in both cities. The rate ratio (RR) in NYC was 3.55 (95% CI 2.40, 5.25), while the RR in Houston was 2.83 (95% CI 1.50, 5.32). Age- and sex-specific standardized hypothermia mortality rates were 18.2 (95% CI 15.1, 21.2) per million in NYC and 30.1 (95% CI 21.7, 38.6) per million in Houston. The comparative hypothermia death ratio was 1.66 (95% CI 1.19, 2.30), indicating hypothermia mortality in Houston was 66% higher than in NYC. There was no correlation between zip code poverty rates and hypothermia-related deaths. The most consistent autopsy finding was Wischnewski spots (56.6%), and ethanol was the most common toxicological finding (36.5%). Local agencies can use this data to target these higher-risk populations and offer appropriate interventions to try to prevent these deaths., (© 2020 American Academy of Forensic Sciences.)

Approximately 50% of the mass of the Envelope (Env) glycoprotein surface subunit (gp120) of human immunodeficiency virus type 1 (HIV-1) is composed of N-linked carbohydrate. Until now, the dogma has been that HIV-1 lacks O-linked carbohydrate on Env. Here we show that a subset of patient-derived HIV-1 isolates contain O-linked carbohydrate on the variable 1 (V1) domain of Env gp120. We demonstrate the presence of this O-glycosylation both on virions and on gp120 expressed as a secreted protein. Further, we establish that these O-linked glycans can confer a more than 1,000-fold decrease in neutralization sensitivity (IC 50 ) to V3-glycan broadly neutralizing antibodies. These findings uncover a structural modification to the HIV-1 Env and suggest a functional role in promoting viral escape from one category of broadly neutralizing antibodies., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

HIV elite controllers represent a remarkable minority of patients who maintain normal CD4 + T-cell counts and low or undetectable viral loads for decades in the absence of antiretroviral therapy. To examine the possible contribution of virus attenuation to elite control, we obtained a primary HIV-1 isolate from an elite controller who had been infected for 19 years, the last 10 of which were in the absence of antiretroviral therapy. Full-length sequencing of this isolate revealed a highly unusual V1 domain in Envelope (Env). The V1 domain in this HIV-1 strain was 49 amino acids, placing it in the top 1% of lengths among the 6,112 Env sequences in the Los Alamos National Laboratory online database. Furthermore, it included two additional N-glycosylation sites and a pair of cysteines suggestive of an extra disulfide loop. Virus with this Env retained good infectivity and replicative capacity; however, analysis of recombinant viruses suggested that other sequences in Env were adapted to accommodate the unusual V1 domain. While the long V1 domain did not confer resistance to neutralization by monoclonal antibodies of the V1/V2-glycan-dependent class, it did confer resistance to neutralization by monoclonal antibodies of the V3-glycan-dependent class. Our findings support results in the literature that suggest a role for long V1 regions in shielding HIV-1 from recognition by V3-directed broadly neutralizing antibodies. In the case of the elite controller described here, it seems likely that selective pressures from the humoral immune system were responsible for driving the highly unusual polymorphisms present in this HIV-1 Envelope. IMPORTANCE Elite controllers have long provided an avenue for researchers to reveal mechanisms underlying control of HIV-1. While the role of host genetic factors in facilitating elite control is well known, the possibility of infection by attenuated strains of HIV-1 has been much less studied. Here we describe an unusual viral feature found in an elite controller of HIV-1 infection and demonstrate its role in conferring escape from monoclonal antibodies of the V3-glycan class. Our results suggest that extreme variation may be needed by HIV-1 to escape neutralization by some antibody specificities., (Copyright © 2019 Silver et al.)

Louis Pasteur's vaccine against rabies was introduced in France during 1885. A year later it became available within the United States. This article tells the story of the first use of the Pasteur vaccine in America and describes the early history of the vaccine's production and distribution across the country by Pasteur Institutes established for this purpose. Highlights of Pasteur's landmark studies on rabies are presented: research which pioneered the field of virology and the use of immunization to prevent infectious diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Despite the higher risk of anal cancer among HIV-infected individuals currently there are no national or international guidelines for anal dysplasia screening. We assessed acceptance and feasibility of screening for anal intraepithelial neoplasia (AIN), the rate of abnormalities, and relationship between the presence of AIN and a history of receptive anal intercourse. Eighty-two percent of HIV-patients approached during routine clinic visit agreed to participate in the study with anal Pap smear collection; 53% had abnormal cytology results and among those undergoing high-resolution anoscopy with biopsy, 55% had high-grade AIN, including 2 cases of carcinoma in situ. Anal cytology was well accepted and it was feasible to be incorporated into HIV primary care practice. Abnormal cytology was not significantly associated with history of anal intercourse (p = 0.767). The high rate of abnormal results reinforces the need for further evaluation of the role of systematic anal Pap smear screening for HIV patients., Competing Interests: Author Disclosure Statement No competing financial interests exist.

We report a case of a 24-year-old immigrant from Bangladesh with Salmonella typhi meningitis, a rare disease in the United States, especially among adults. The common manifestations of meningitis such as neck rigidity and changes in mental status did not develop and Kernig sign was absent. The patient was successfully treated with intravenous ceftriaxone. This case demonstrates the importance of considering endemic infections in the country of origin when recent immigrants and returnees to the United States present with febrile illness.

Invasive pneumococcal disease (PD) occurs frequently among HIV-infected patients, but it is unclear whether its manifestations and outcome are different compared to those observed among patients without HIV-1 infection. Because the immune reconstitution that accompanies antiretroviral therapy may change some of these features and because most cases of HIV- 1 infection occur in resource-poor settings of the world where access to antiretroviral agents is limited, we compared PD among patients with and without HIV-1 infection in a North American population before the introduction of highly active antiretroviral therapy (HAART). The records of all pneumococcal cultures processed at this medical center over a period of 20 months were used to identify patients with invasive PD. Hospital records were reviewed for 103 of these patients (52 with and 51 without HIV-1 infection) and demographic, clinical, laboratory, radiographic, and microbiologic information was abstracted and subsequently analyzed. Despite similarities in presenting signs and symptoms, we found a higher incidence of bacteremia but a more favorable outcome with less frequent requirements for intubation and admission to intensive care units and better survival among individuals with HIV infection. Factors such as less advanced age, the presence of fewer comorbid conditions, or a less florid inflammatory response among HIV-infected individuals may account for differences in outcome of invasive PD.

Highly active antiretroviral therapy directed against HIV-1 has dramatically modified morbidity and mortality in infected individuals. Enthusiasm for the success of these medications have been tempered by an inability to clear virus from the infected host leaving a virus poised to leverage any advantage into one of productive survival. One mechanism used to accomplish escape from suppression secondary to antiretroviral therapy is by developing mutations. The goal of therapy has been to diminish viral replication, thereby effectively abrogating the development of these resistance-bearing mutations. This strategy has met with significant success but numerous host-viral factors impact on the ability of the clinician to persistently suppress viral load, thereby providing a window of opportunity for the virus to mutate. In particular we review evidence for ongoing viral replication in the face of suppressive antiretroviral therapy and viral replication in tissue compartments. We discuss whether viral resistance can develop during transient elevations in viral load (viral blips) or as a function of the rate of viral load decay while on therapy. Finally, we touch on the therapeutic strategy that diminished viral replication capacity of mutational species can maintain host immunity.

Objective: In this study we evaluated the possibility that plasma viral load elevations secondary to influenza vaccination in HIV-1-seropositive individuals with previously undetectable viral loads (< 200 copies/ml) could develop resistance-bearing mutations in the viral reverse transcriptase (RT) and protease regions., Methods: Thirty-four patients with undetectable viral burdens on highly active antiretroviral therapy (HAART) were evaluated for elevations in plasma viral load 2 and 4 weeks post-influenza vaccination. Plasma from patients whose viral load increased after vaccination was subject to genotypic resistance analysis by the line probe assay (LiPA) to determine whether primary resistance-bearing mutations developed during this period and at follow-up. Stored plasma was used to evaluate whether RT or protease mutations existed pre-vaccination., Results: Seven out of 34 patients were found to experience elevations in their viral load after influenza vaccination. Two of the patients revealed evidence of primary RT or protease mutations not demonstrated in earlier pre-vaccination samples. One patient failed therapy after vaccination, and one patient revealed post-vaccination viral load elevations that eventually led to the progressive development of primary zidovudine mutations., Conclusion: Evidence is presented that supports the contention that a small subset of patients who experience viral load elevations after influenza vaccination can develop mutational changes in the RT region of the viral genome either acutely or after a failure of the viral load to return to undetectable levels.

Disease-specific registries have many important applications in epidemiologic, clinical and health services research. Since 1989 the Department of Veterans Affairs has maintained a national HIV registry. VA's HIV registry is national in scope, it contains longitudinal data and detailed resource utilization and clinical information. To describe the structure, function, and limitations of VA's national HIV registry, and to test its accuracy and completeness. The VA's national HIV registry contains data that are electronically extracted from VA's computerized comprehensive clinical and administrative databases, called Veterans Integrated Health Systems Technology and Architecture (VISTA). We examined the number of AIDS patients and the number of new patients identified to the registry, by year, through December 1996. We verified data elements against information obtained from the medical records at five VA sites. By December 1996, 40,000 HIV-infected patients had been identified to the registry. We encountered missing data and problems with data classification. Missing data occurred for some elements related to the computer programming that creates the registry (e.g., pharmacy files), and for other elements because manual entry is required (e.g., ethnicity). Lack of a standardized data classification system was a problem, especially for the pharmacy and laboratory files. In using VA's national HIV registry we have learned important lessons, which, if taken into account in the future, could lead to the creation of model disease-specific registries.

Pulmonary nocardiosis is an uncommon but serious infection that is increasingly found in immunosuppressed persons, especially transplant recipients and persons with AIDS. The Nocardia species are denizens of soil and decaying plants that gain entry to humans through inhalation or inoculation. Pulmonary nocardiosis typically presents as an acute to subacute necrotizing pneumonia, with a variable clinical picture. Metastatic infections of the brain and subcutaneous tissues are common complications. Most clinical laboratories can isolate these microorganisms, but final speciation may be a challenge and antimicrobial susceptibility testing is especially difficult because of the slow rate of growth of Nocardia species. Full identification of species and susceptibility testing is important because of the epidemiologic implications and the difficulties of successfully treating these infections in immunosuppressed patients. Sulfonamides, including trimethoprim-sulfamethoxazole, remain the most reliable antimicrobials. Many alternative agents are active against Nocardia in vitro, but clinical data are limited.

Pneumocystis carinii pneumonia (PCP) is one of the most common reasons for the hospitalization of AIDS patients; however, geographic differences in PCP management have not been evaluated previously. Therefore, we abstracted data on socioeconomic characteristics, prior HIV care, severity of illness, timeliness and intensity of in-hospital care, duration of hospitalization, and survival from 1547 randomly selected medical records of patients hospitalized with AIDS-related PCP between 1987 and 1990 at 82 hospitals in Chicago, Los Angeles, Miami, New York City, and Raleigh-Durham, North Carolina. Multivariate regression models were used to assess factors associated with longer hospital stays and increased inpatient mortality. Our results showed that in-hospital mortality ranged from 15% to 27%, bronchoscopy rates from 53% to 70%, and mean length of stay from 14 days to 23 days. Geographic variations in mortality were accounted for by differences in severity of illness at admission, insurance status, and in-hospital patient management. However, significant regional variations in hospital length of stay persisted, even after adjusting for patient demographics, severity of illness, and use of diagnostic and therapeutic care resources.

Background/objective: Previous studies have identified large variations in patterns of in-hospital acquired immunodeficiency syndrome (AIDS) care among groups of hospitals and physicians. We evaluated the patterns of care for patients with AIDS-related Pneumocystis carinii pneumonia (PCP) care at a single university program with patients treated at an adjacent county and Veterans' Administration (VA) hospital. All medical care was provided by physicians in a single residency program, but attending physician staffs were separate., Setting and Patients: A randomized sample of patients with human immunodeficiency virus (HIV)-related PCP from the two hospitals who received care between 1987 and 1990., Results: During the study years, the VA hospital provided care for approximately one fourth as many AIDS patients as the county hospital. Patients at the VA hospital had a higher bronchoscopy rate (39.7% versus 27.7%, P = .05), higher intensive-care unit (ICU) rate (11.8% versus 2.9%, P = .008), longer hospitalizations (mean length of stay of 18.9 versus 13.9 days, P = .004), but delayed initiation of anti-PCP therapy (median of day 2 versus day 1, P < .05). The odds of death were significantly different between the VA and county hospitals, even after adjusting for differences in important patient characteristics., Conclusion: Patterns of in-hospital PCP care differed between the two hospitals of this medical school. Possible explanations include organizational differences related to level of attending physician HIV experience, hospital case loads of AIDS patients, or specific hospital considerations such as concerns over tuberculosis exposure.

To determine whether patient and hospital characteristics were significantly associated with variations in Pneumocystis carinii (PCP) care and outcomes, we analyzed the use of diagnostic tests, intensive care units (ICUs), anti-PCP medications for persons hospitalized with human immunodeficiency virus (HIV)-related PCP, and hospital discharge status. We conducted retrospective chart reviews of a cohort of 2,174 patients with PCP hospitalized in 1987-1990. Outcomes included process of care for PCP and in-hospital mortality rates. Persons with PCP who were more severely ill at admission were more likely to have early medical care, to receive care in an intensive care unit, and to die in hospital. After we adjusted for differences in this severity of illness, we noted that Medicaid patients, injection drug users (IDUs), and patients treated at VA or county hospitals were significantly less likely than others to have diagnostic bronchoscopies and that persons covered by Medicaid, with a previous diagnosis of acquired immunodeficiency syndrome (AIDS), who did not receive prior zidovudine (AZT) or who received care in a VA hospital had the highest chances of in-hospital death. Insurance and risk group characteristics, severity of illness, and hospital characteristics appear to be the most important determinants of the intensity and timing of medical care and outcomes among patients hospitalized with PCP.

Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies).

The objective of the present study was to assess the association between type of health insurance coverage and use of diagnostic tests and therapies among patients with AIDS-related Pneumocystis carinii pneumonia (PCP). Fifty-six private, public, and community hospitals in Chicago, Los Angeles, and Miami were selected for the study, and the charts of 890 patients with empirically treated or cytologically confirmed PCP, hospitalized during 1987 to 1990 were retrospectively reviewed. Patients were classified by insurance status: self-pay (n = 56), Medicaid (n = 254), or private insurance, including health maintenance organizations and Medicare (n = 580). Primary outcomes were the use and timing of bronchoscopy, the type and timing of PCP therapy, and in-hospital mortality. The results indicate that Medicaid patients were less likely than privately insured patients to undergo bronchoscopy (relative odds = 0.61; 95% CI = 0.40, 0.93; p = 0.02) or to have their diagnosis of PCP confirmed (relative odds = 0.51; 95% CI = 0.33, 0.77), after adjusting for patient, severity of illness, and hospital characteristics. Medicaid patients were approximately three-fourths more likely than privately insured patients (relative odds = 1.73; 95% CI = 1.01, 2.96; p = 0.04) to die in-hospital, after adjusting for patient, severity of illness, and hospital characteristics. However, with further adjustment for confirmation of PCP, Medicaid patients no longer had a significantly higher likelihood of dying in-hospital. We conclude that Medicaid patients are less likely to receive diagnostic bronchoscopy than privately insured or self-insured patients, more likely to be empirically treated for PCP, and more likely to die in-hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrobial agents are used to prevent infections in a variety of clinical circumstances. In certain instances, the precise indications for prophylaxis remain controversial, and the preferred regimens undergo alterations based upon evolving clinical experience, changing patterns of microbial susceptibility, and innovations in medical and surgical practice. This article outlines the general principles underlying the use of antimicrobial prophylaxis and presents recommendations for the use of such prophylaxis in three areas: (1) surgery involving contaminated, clean-contaminated, and clean procedures; (2) prevention of infections due to specific pathogens, including Neisseria meningitidis, Hemophilus influenzae, Streptococcus pneumoniae, and Streptococcus pyogenes; and (3) prevention of infective endocarditis.

Many patients infected with the human immunodeficiency virus (HIV) with symptoms suggestive of pneumonia are treated empirically for Pneumocystis carinii pneumonia (PCP), although other bacterial infections (e.g., tuberculosis) and pulmonary Kaposi's sarcoma may cause identical symptoms. Empiric treatment for PCP may result in misdiagnosis and mistreatment. When the outcomes of cytologically confirmed versus empirically treated PCP cases were evaluated, the most important predictors of in-hospital mortality were severity of illness and use of bronchoscopy. Persons who did not undergo bronchoscopy had higher mortality rates than patients negative by bronchoscopy or cytologically confirmed as positive for PCP (22% vs. 11% vs. 14%, P < .01), although severity of illness and timing of anti-PCP medications did not differ significantly. Compared with cytologically confirmed cases, persons who did not have bronchoscopy were more likely to die than were bronchoscopy-negative patients (P < .05), after adjusting for severity of illness. Bronchoscopy use may have contributed to better outcomes for persons treated for HIV-related PCP.

Pneumocystis carinii pneumonia (PCP) has been the most common reason for hospitalization and the most common cause of death for persons with HIV infection. Hospital mortality rates for PCP range from 10 to 60%. Studies that evaluate differences in hospital mortality rates must control for differences in patient severity of illness. We developed a simple staging system for categorizing severity of illness in patients with PCP. We analyzed the relation between clinical factors and in-hospital mortality for 576 hospitalized patients with HIV-related PCP treated at 56 hospitals for the years 1987 to 1990. Four stages of PCP could be identified based on three routinely measured clinical variables: alveolar-arterial oxygen difference, total lymphocyte count, and body mass index. The mortality rate increased by stage: 1% for Stage 1, 8% for Stage 2, 23% for Stage 3, and 48% for Stage 4. The four-stage severity system compared well with previous models developed for AIDS and for PCP, and is easier to use in clinical practice. Our staging system identifies patients with a high and low risk of in-hospital death upon admission. Physicians may benefit from consideration of PCP stage in deciding on management strategies. In addition, researchers involved in clinical trials of new agents for PCP might consider stratification by PCP stage in order to define homogenous groups.

A leading cause of biliary tract disease and pancreatitis worldwide is parasitic disease. In the United States, increased global travel and the AIDS epidemic has led to a rise in the frequency of parasitic disease. Biliary disease and pancreatic disease secondary to parasitic infestation is relatively new in this country, with the first case being described in 1977. These diseases are no longer the exclusive realm of infectious disease specialists and require general practitioners and gastroenterologists to be well versed in the spectrum of parasitic pancreatic and biliary disease.

A total of 30 patients (aged 6-56 years) with nocardiosis and infection due to human immunodeficiency virus type 1 (HIV-1) were identified in our institution between January 1985 and June 1989. Eighteen patients had an AIDS-defining illness before or concurrently with nocardiosis. The mean CD4 lymphocyte count was 109/mm3. Pulmonary nocardiosis in 21 patients, extra-pulmonary nocardiosis in 8, and pulmonary and extrapulmonary nocardiosis in 1 patient was diagnosed. Chest radiographs showed alveolar patterns of infiltrates in 14 patients, reticulonodular patterns in 2, mixed alveolar and reticulonodular patterns in 6, cavitation in 4, and pleural effusion in 3. Of 27 patients treated, the conditions of 22 improved, but the extensive disease in 5 progressed. For 14 patients, recurrence was rapid after their treatment was discontinued. Nocardiosis caused or contributed to the death of 19 patients; in six patients, there was no evidence of nocardial infection at death. Nocardiosis can be a fatal complication of advanced HIV-1 disease. Delayed diagnosis, extensive disease, and early discontinuation of treatment were associated with poor outcome.

The successful development of synthetic materials and introduction of artificial devices into nearly all body systems has been shadowed by the adaptation of microorganisms to the opportunities these devices afford for eluding defenses and invading the host. Clinicians are faced with the task of recognizing the manifestations of device-associated infection, predicting the likely pathogens involved, knowing the appropriate diagnostic methods, and initiating appropriate therapy. Infections associated with prosthetic heart valves are particularly challenging to successfully treat; surgical replacement may be necessary. Infection associated with an artificial joint usually requires removal of the device in addition to appropriate antibiotics. Intravascular associated infections are the leading cause of nosocomial bacteremias and, because of their intravascular location, these infections are often life catheter threatening if not promptly diagnosed and treated. Even contact lenses, external to epithelial surfaces, may give rise to serious sight-threatening infections. Although artificial devices play a paramount role in medicine today, infection is an ever present potential with which clinicians must be familiar.

Background: Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established., Methods: We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed., Results: During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash., Conclusions: In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.

To validate an automated AIDS severity-of-illness prognostic algorithm, 2,113 discharge summaries of HIV-infected patients were merged with the Problem-Oriented Medical Synopsis (POMS) and an HIV risk registry. The combination of a medically derived classification and staging algorithm with multivariate statistical techniques was used for automated severity-of-illness disease staging and prognostic assignment. The model correctly predicted the outcomes of 82% of all cases (death, survivorship) at discharge, and 66% of deaths.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin and placebo was conducted at four medical centers. One hundred sixty-four adult men with lymphadenopathy were enrolled over a 2-month period and randomized to receive ribavirin 800 mg (53 subjects), ribavirin 600 mg (55 subjects), or placebo (56 subjects). Active treatment was administered for 24 weeks followed by a 4-week washout period. Nine subjects receiving placebo, four receiving ribavirin 600 mg, and none in the 800 mg group developed AIDS during the 24 weeks of active treatment. One patient randomized to the 800 mg group had Kaposi's sarcoma at study entry and was included in the intent-to-treat analysis. An overall significant difference in progression to AIDS was observed among the three treatment groups (p = 0.028) with patients randomized to receive 800 mg having a significantly longer time to AIDS than placebo patients (p = 0.012; relative risk, 9.0; 95% confidence interval, 1.1 to 70.8). There was no significant difference between the 600 mg and placebo groups (p = 0.15; relative risk, 2.3; 95% confidence interval, 0.7 to 7.6). Baseline CD4 cell count and hematocrit made independent contributions and formed a multivariate prognostic set for these progression data. The significant treatment superiority of 800 mg compared to placebo remained after adjustment for these factors (p = 0.019). After deletion of patients with major protocol violations at entry, the difference between the 800 mg and placebo treatment remained significant (p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty Haitian patients, hospitalized from 1 April 1980 to 20 June 1982, had Pneumocystis carinii pneumonia, central nervous system toxoplasmosis, esophageal candidiasis, cryptococcosis, disseminated cytomegalovirus, progressive herpes simplex virus, chronic enteric coccidiosis, or invasive Kaposi's sarcoma. Ten patients died. Opportunistic infections were frequently multiple and were recurrent in three patients. In seven patients disseminated tuberculosis preceded the other infections by 2 to 15 months. There was no evidence of an underlying immunosuppressive disease, and no history of homosexuality or intravenous drug abuse. At least three patients probably acquired the syndrome in Haiti. Lymphadenopathy was common. Seventeen patients tested had anergy, and 18 had lymphopenia. Monoclonal antibody analysis of peripheral-blood T-cell subsets done on 11 patients showed a marked decrease in T-helper cells and an inversion of the normal ratio of T-helper cells to T-suppressor cells. This syndrome among heterosexual Haitians is strikingly similar to the syndrome of immunodeficiency described recently among American homosexuals.

A patient with meningitis caused by a strain of Actinetobacter anitratus that was resistant to all commercially available antibiotics was treated with imipenem/cilastatin administered intravenously in a dose of 1 gm of imipenem every six hours. The minimal inhibitory concentration of imipenem against the isolate was less than or equal to 0.04 micrograms/ml. The patient tolerated the drug well and was cured after 12 days of therapy.

The safety and efficacy of sulfamethoxazole and trimethoprim in the prevention of Pneumocystis carinii pneumonia associated with the acquired immunodeficiency syndrome (AIDS) were evaluated. Sixty patients with a new diagnosis of Kaposi's sarcoma and no history of opportunistic infections were randomly assigned to receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice per day or no therapy. None of the 30 patients receiving sulfamethoxazole and trimethoprim developed P carinii pneumonia. Sixteen of the 30 patients receiving no suppressive therapy developed P carinii pneumonia. Development of P carinii pneumonia was associated with the stage of Kaposi's sarcoma, B subtype disease, and the presence of 0.20 X 10(9)/L (200/mm3) or fewer CD4 cells at study entry. The proportion of patients surviving and the mean length of survival were significantly greater in the treatment group compared with the control group. Adverse reactions occurred in 15 patients (50%).

Multiple opportunistic infections are characteristic of the acquired immunodeficiency syndrome (AIDS). Although bacterial pathogens have presented few problems, we have noted an emerging problem with salmonellal infection among patients with AIDS. A review of all stool and blood cultures from adults between January 1982 and July 1984 showed that 80 stool cultures were positive for Salmonella species; serogroup B was the most common isolated. Eight (10%) were isolated from patients with AIDS. Nineteen blood cultures were positive for Salmonella species. Six (32%) were isolated from patients with AIDS: three were positive for Salmonella serogroup B; two yielded Salmonella choleraesuis; and one yielded Salmonella serogroup D. In three (50%), Salmonella bacteremia was a presenting manifestation of AIDS. Bacteremias were recurrent in five patients. Thus, it appears that AIDS not only predisposes patients to serious salmonellal infections but also compromises their ability to eradicate these bacteria.

Sixteen mothers of 22 infants with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were followed up for evidence of clinical and immunologic abnormalities. With one exception, all mothers were clinically well at delivery but had evidence of immune dysfunction, with T-cell abnormalities and inverted T4/T8 ratios and/or elevation of serum immunoglobulin levels, particularly of IgG. During a follow-up period that averaged 30 months, AIDS developed in five of the mothers and AIDS-related complex in seven. Twelve subsequent pregnancies in 11 mothers produced four affected infants, suggesting that mothers can be persistently infected. Six mothers were delivered of subsequent infants who remain unaffected. These results suggest that the mothers are the likely source of infection in non-transfusion-associated cases of AIDS or AIDS-related complex in infants, that mothers have persistent immunologic abnormalities, and that they are at increased risk of developing AIDS or AIDS-related complex.

A case of subcutaneous phaeohyphomycosis in a human, involving the ankle and caused by Scytalidium lignicola, is described. The isolate was found to be sensitive to amphotericin B, 5-fluorocytosine, miconazole, and ketoconazole in vitro.

Cerebrospinal fluid of aztreonam were measured in 11 patients with meningeal inflammation. Two to eight hours after a single 2 gm intravenous dose, CSF aztreonam levels ranged from 0.76 to 16.6 mg/l. The mean CSF concentration in four patients with viral meningitis was 1.28 mg/l, which was lower than the mean concentration of 7.2 mg/l in the five with bacterial, cryptococcal or carcinomatous meningitis. Two patients with infected subdural drains were also sampled serially and had CSF levels greater than 1 mg/l between 1 and 8 h post dose. Penetration of aztreonam into the CSF in the presence of meningeal inflammation appears adequate to warrant therapeutic trials in patients infected with susceptible organisms.

Forty-five adults with the acquired immunodeficiency syndrome (AIDS) and their 45 spouses, 109 children, and 29 household contacts were studied for evidence of heterosexual, perinatal, and household spread of human T-cell lymphotropic virus type III (HTLV-III) infection. Of the 45 spouses enrolled, 26 (58%) had antibody to HTLV-III, including 12 (71%) of 17 male spouses and 14 (50%) of 28 female spouses. Of the 12 seropositive male spouses, nine were seropositive at enrollment and three had seroconversion. Of the 14 seropositive female spouses, four were seropositive at enrollment and ten seroconverted. Lack of barrier contraceptive use and oral sex were associated with seroconversion. Of the 109 children enrolled, 15 had AIDS or an AIDS-related illness, two had evidence of passive transfer of maternal antibodies, and two had HTLV-III infection acquired outside the household. None of the 90 seronegative children seroconverted. Of 29 household contacts studied, none developed antibody to HTLV-III.

Thirty-six patients with AIDS and culture-proven nontuberculous mycobacteriosis were compared to 20 patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis with regard to clinical signs, symptoms, and diagnostic methods. Patients with nontuberculous mycobacteriosis were more often younger and homosexuals, while patients with tuberculosis were usually Haitian-American or users of intravenous drugs. A majority of patients with tuberculosis presented with fever and weight loss. These symptoms were seen in approximately 50 percent of the patients with nontuberculous mycobacteriosis. A distinct syndrome of dyspnea, chills, hemoptysis, and chest pain was seen in a significant minority of patients with nontuberculous mycobacteriosis. Lymphadenopathy was seen almost exclusively in patients with tuberculosis. Pulmonary sources (expectorated sputum or bronchoscopy specimens) were the most common source of diagnosis in both groups. Patients in both groups in whom the diagnosis was obtained from pulmonary sources frequently had negative chest x-ray films on presentation. Cavitary disease was absent from both groups.

A broad spectrum of gastrointestinal pathogens can cause diarrhea in patients with acquired immunodeficiency syndrome (AIDS). A systematic approach utilizing symptomatology and the appropriate diagnostic tests will maximize the clinician's chance of identifying the specific pathogens. Enteric infections in AIDS patients are often incurable and require prolonged therapy and chronic suppression. Experimental agents show promise of decreasing the morbidity and mortality attendant on diarrhea in AIDS patients.

Piperacillin, a new semisynthetic penicillin, was evaluated for efficacy and safety in 26 patients, most of whom had pneumonia. Included were four patients with gram-negative meningitis in whom the penetration of piperacillin into cerebrospinal fluid was determined. Cure was achieved in 11 of 17 patients with pneumonia; another 4 were improved. One relapse and one failure occurred among nine patients with gram-negative pneumonia. Cure or improvement occurred in seven of nine patients with gram-negative infection in various extrapulmonary sites. Piperacillin given by continuous infusion in a dosage ranging from 324 to 436 mg/kg of body weight per day to four patients with meningitis resulted in a mean cerebrospinal fluid level of 23 micrograms/ml at 24 h; the mean penetration of piperacillin into the cerebrospinal fluid was 32% at this interval. Levels of piperacillin in cerebrospinal fluid collected later during the course of therapy were also adequate. Adverse effects were noted in six patients, but only one episode of granulocytopenia was serious. Emergence of resistance to piperacillin did not occur, and only one superinfection was noted. Piperacillin appeared to be efficacious in the treatment of pneumonia. It penetrated well into the cerebrospinal fluid of patients with meningitis and may be useful for treatment of selected gram-negative infections in extrapulmonary sites.

Characteristic pathological alterations of the liver in chimpanzees inoculated with non-A, non-B hepatitis sera have been described, but no corresponding findings have been reported in humans. Electron microscopic studies of the liver biopsy specimens of two homosexual patients with acquired immune deficiency syndrome, one without hepatitis (Patient 1) and one with chronic active hepatitis in remission (Patient 2), revealed the cytoplasmic tubular structures which are characteristic of chimpanzee non-A, non-B hepatitis. A cluster of 23 nm double-shelled particles was also seen in the cytoplasm of a hepatocyte in patient 1 who had received a blood transfusion 8 days before the biopsy. These particles were smaller than the Dane particles, Epstein-Barr virus, cytomegalovirus or herpes simplex virus, and different from hepatitis A virus particles; the antibodies to all of which are found in high concentration in acquired immune deficiency syndrome patients. These observations may reflect the morphologic findings for non-A, non-B hepatitis infection in humans.

The minimal inhibitory concentrations of piperacillin and seven other betalactam antibiotics were determined against 407 bacterial isolates. Piperacillin was found to be more active than ampicillin against susceptible gram-negative bacilli and more active than either carbenicillin or ticarcillin against Pseudomonas aeruginosa and streptococci. Although piperacillin was active against Klebsiella pneumoniae, this activity was less than that of the cephalosporins. Piperacillin was not active against penicillin-resistant Staphylococcus aureus and Enterobacteriaceae that were resistant to the other test antibiotics.