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Outcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unclear.Associations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models.Among 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94 [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65, 4.73]; P = 0.008), after accounting for VACS Index. Readmission was not associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714).Among HIV-infected and uninfected older adults hospitalized for CAP, organ system components of the VACS Index were associated with adverse CAP outcomes. Among HIV-infected individuals, ART was associated with decreased 30-day mortality and LOS.

Community viral load (CVL) estimates vary based on analytic methods. We extended the CVL concept and used data from the Veterans Health Administration (VA) to determine trends in the health care system viral load (HSVL) and its sensitivity to varying definitions of the clinical population and assumptions regarding missing data.We included HIV-infected patients in the Veterans Aging Cohort Study, 2000-2010, with at least one documented CD4 count, HIV-1 RNA or antiretroviral prescription (n = 37 318). We created 6-month intervals including patients with at least one visit in the past 2 years. We assessed temporal trends in clinical population size, patient clinical status and mean HSVL and explored the impact of varying definitions of the clinical population and assumptions about missing viral load.The clinical population size varied by definition, increasing from 16 000-19 000 patients in 2000 to 23 000-26 000 in 2010. The proportion of patients with suppressed HIV-1 RNA increased over time. Over 20% of patients had no viral load measured in a given interval or the past 2 years. Among patients with a current HIV-1 RNA, mean HSVL decreased from 97 800 HIV-1 RNA copies/mL in 2000 to 2000 copies/mL in 2010. When current HIV-1 RNA data were unavailable and the HSVL was recalculated using the last available HIV-1 RNA, HSVL decreased from 322 300 to 9900 copies/mL. HSVL was underestimated when using only current data in each interval.The CVL concept can be applied to a health care system, providing a measure of health care quality. Like CVL, HSVL estimates depend on definitions of the clinical population and assumptions about missing data.

To describe the natural history of Mycobacterium avium complex (MAC) in the respiratory or gastrointestinal tract of persons with human immunodeficiency virus (HIV) infection, 67 HIV-infected patients with CD4+ cell counts < 200/mm3 and initial negative MAC blood cultures were followed prospectively. Patients were screened every 3 months with cultures and smears of sputum, rectal swab, and blood for mycobacteria. Fourteen patients (20.9%) developed positive blood cultures for MAC (23.4%/year). Sputum cultures revealed MAC in 3 (21%) of the 14 patients at 1, 2, and 8 months before dissemination; no smears were positive. No rectal swab cultures or smears were positive before dissemination. Colonization of the respiratory and gastrointestinal tracts in persons with HIV infection and < 200/mm3 CD4+ cells is infrequently detected with currently available techniques. Screening cultures and smears of sputum and stool do not appear to be sensitive methods for detection of early MAC infection.

Candida albicans strain diversity and fluconazole resistance were prospectively analyzed in oral strains from 29 adult human immunodeficiency virus (HIV)-positive patients followed for > 1 year who had five or more culture-positive clinic visits. Molecular typing consisted of genomic blots probed with the Ca3 repetitive element. Sixteen patients had one or more episodes of oropharyngeal candidiasis (OPC), 12 (75%) maintained the original genotype, whereas the remaining four patients had a succession of 2-3 genotypes. The original genotype, either alone or mixed with another strain or with non-C. albicans Candida spp., was recovered from oral lesions in 13 of 15 evaluable (86.7%) patients. C. dubliniensis was the infecting yeast in the remaining two patients. Different patterns of fluconazole resistance occurred in three OPC patients. One patient's infecting strain became less susceptible. A second patient was infected with a resistant genotype and a progressively more susceptible minor genotype variant. C. dubliniensis isolates from the third patient varied in susceptibility. Thirteen colonized patients who never developed OPC harbored a greater variety of C. albicans genotypes (2-6) than their infected counterparts (P = 0.35). OPC patients maintained their original endogenous C. albicans strains for prolonged periods, whether or not they demonstrated decreased in vitro susceptibility to fluconazole. The adaptation and maintenance of an endogenous C. albicans strain within its host may be linked to as yet uncharacterized factors.

Objective To measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets, measures of disease activity, and response to highly active antiretroviral therapy (HAART). Design Fourteen untreated HIV-1-infected patients, 18 patients at 3-to 4-weeks after beginning HAART, and 35 uninfected control subjects were studied. Methods Four-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure their expression of CCR5, CXCR4, and CD38. Results HIV-1-infected patients had higher CCR5 levels and lower CXCR4 levels on CD4 and CD8 T cells and their CD45RO/CD45RA subsets than control subjects did. However, CCR5 elevation was statistically significant only for CD4 T cells and their subsets, and CXCR4 depression was significant for CD8 T cells and their subsets (and for CD4:CD45RO cells). The elevation of CCR5 and depression of CXCR4 were not due to shifts in CD45RO/CD45RA subset proportions but to upregulation or downregulation within the subsets. CCR5 elevation on CD4 T cells was significantly restored toward normal by HAART, but the CXCR4 depression was not. CCR5 expression but not CXCR4 expression correlated with other measures of immunodeficiency (CD4 T-cell levels), active infection (viral load), and cellular activation (CD38). Conclusions CCR5 elevation is a concomitant of immune activation and viral replication that occurs in HIV-1 infection, but the relation of CXCR4 depression to severity of infection, disease progression, and response to therapy remains undefined.

The Association for Professionals in Infection Control and Epidemiology, Inc (APIC) is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.

The Association for Professionals in Infection Control and Epidemiology, Inc. (APIC) is a multidisciplinary organization of more than 11,000 health care professionals who practice infection control and epidemiology within a variety of health care settings. As an authority in infection control, APIC endorses the Advisory Committee on Immunization Practices (ACIP) recommendations that are published by the Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. APIC supports the immunization initiative of the Healthy People 2000: National Health Promotion and Disease Prevention Objectives, which contains a national strategy for significantly improving the health of the nation, including preventing infectious diseases through immunization.

Disseminated Mycobacterium avium complex (MAC) infection continues to be a common opportunistic infection in patients infected with human immunodeficiency virus (HIV). The optimal therapy for disseminated MAC infection is unclear. We compared azithromycin plus ethambutol with clarithromycin plus ethambutol in the treatment of disseminated MAC infection in HIV type 1-infected patients, examining the frequency of bacteremia clearance, time to clearance, and study drug tolerance after 16 weeks of therapy. Fifty-nine patients for whom blood cultures were positive for MAC were enrolled in the study from 10 university-affiliated Veterans Affairs Medical Centers. Thirty-seven patients were evaluable for determination of quantitative bacteremia and clinical outcomes. Clearance of bacteremia was seen at the final visit in 37.5% of azithromycin-treated patients and in 85.7% of clarithromycin-treated patients (P = .007). The estimated median time to clearance of bacteremia was also significantly different between the two treatment arms: 4.38 weeks for clarithromycin recipients vs.16 weeks for azithromycin recipients (P = .0018). Only one isolate developed macrolide resistance during therapy. Abatement of symptoms, other laboratory-evident abnormalities, and adverse effects were similar in the two groups. At the doses used in this study, clarithromycin/ethambutol produced a more rapid resolution of bacteremia than did azithromycin/ethambutol, and clarithromycin/ethambutol was more effective at sterilization of blood cultures after 16 weeks of therapy.

Cladophialophora bantiana causes a rare phaeohyphomycosis, usually manifested by brain abscesses but rarely by skin or pulmonary lesions. It has not been reported as a common colonizer or as a cause of pulmonary symptoms in patients with AIDS. We present a case in which C. bantiana was repeatedly isolated from the sputum of a patient with AIDS having pulmonary infiltrates.

Meningitis is a frequent complication of the human immunodeficiency infection. Possible causes include bacterial, fungal, mycobacterial, syphilitic, and vital pathogens (including the human immunodeficiency virus). Drugs must also be considered in the differential diagnosis. Two patients with probable trimethoprim-sulfamethoxazole-induced meningitis are described in the setting of human immunodeficiency virus infection.

Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of200/microL (or prior AIDS-defining opportunistic infection), and the presence of serum IgG to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary.

Recognizing the unique needs and demands of HIV-infected patients, it was decided to implement pharmaceutical care in a VAMC outpatient HIV clinic. Services provided to the patients by the pharmacist include drug information, medication counseling with the help of educational handouts, and drug-related problem identification and resolution. The pharmacist also serves as a liaison between the patient and the VAMC outpatient pharmacy if conflicts arise. Services provided to the other members of the HIV clinic team include the provision of drug information and participation in clinical research. In addition, the HIV clinic provides a training site for pharmacy practice residents and Doctor of Pharmacy students on their ambulatory care rotation.

A patient with common variable hypogammaglobulinemia (CVH) who presented with recurrent sinopulmonary infections, nodular lymphoid hyperplasia of the small bowel, and intestinal giardiasis was studied. A diffuse lymphocytic lymphoma with small bowel, skin, and hepatic involvement subsequently developed in the patient. Light microscopy of the tumor revealed tissue infiltration with mononuclear cells having the morphologic features of T-lymphocytes. The malignant lymphocytes had characteristics of T-suppressor/cytotoxic cells as established by the absence of surface immunoglobulin and Leu 3 surface markers, and the presence of OKT3 and OKT8 surface markers. Peripheral blood lymphocyte studies revealed an increased number of T-suppressor cells, a reversal of the helper-suppressor ratio, and a generalized state of hyporesponsiveness to mitogen and antigen stimulation. No evidence of retroviral reverse transcriptase activity was detected in cultures of peripheral blood lymphocytes. The association between CVH and a lymphoma composed of cells with T-suppressor/cytotoxic surface markers has not been previously reported. The postulated role of T-suppressor cells in the failure of immunoglobulin synthesis in some forms of CVH suggests that the finding of a T-suppressor/cytotoxic cell lymphoma complicating CVH may be more than fortuitous.

An outbreak caused by influenza A/Philippines/2/82 (H3N2)-like viruses occurred in a partially vaccinated nursing home population in January 1985. During the first six days of the outbreak, 14 (25%) of 55 residents developed influenzalike illness. The risk of illness was most strongly associated with undetectable levels of antibody against the epidemic strain, with unvaccinated case-patients having more severe illnesses and a higher rate of hospitalization than vaccinated case-patients (5/8 vs 0/6). During the period of amantadine hydrochloride prophylaxis (100 mg/d) from days 7 to 35, only two (5%) of the remaining 41 residents became ill, even though 11 (27%) had no detectable antibody. Serum amantadine levels obtained on day 35 ranged from 117 to 737 ng/mL (mean 309 ng/mL), similar to therapeutic levels documented in younger adults who have taken the standard regimen of 200 mg/d; there were few clinically significant side effects. These findings illustrate the benefits of influenza vaccination and support the use of amantadine hydrochloride at a dosage of 100 mg daily for outbreak control among elderly persons.

Acquired immune deficiency syndrome, or AIDS, is an unexplained severe disturbance of the cell-mediated immune system that renders victims susceptible to a group of otherwise-rare diseases and infections, chiefly Kaposi's sarcoma and Pneumocystis carinii pneumonia. AIDS has been the object of intensive research since mid-1981 when the syndrome was first described by the Centers for Disease Control (CDC). The victims fall into four main group: homosexually-active males, IV drug users, Haitians, and hemophiliacs. The CDC has noted a doubling of AIDS cases every six months, with the current count--as of June 27, 1983--being 1,676, and the overall mortality rate 39%. The outbreak is most severe in New York City, with the remainder concentrated primarily in other major American cities. Cases have also been reported in 38 states, Washington, D.C., and Puerto Rico. At present there are no specific diagnostic tests (diagnosis is primarily clinical), and there is still no specific treatment.

Several defects in host defense mechanisms of chronic alcoholics have been described, but the effect of ethanol on the alveolar macrophage has not been defined. Monolayers of rabbit alveolar macrophages established on plastic culture dishes were exposed to various agents to evaluate the maintenance of adherence. Ethanol produces a rapid onset loss of adherence in this system. The loss of adherence is (1) dose-dependent, (2) transient despite the continued presence of ethanol, and (3) due to a change in the macrophage. Similar rapid-onset, transient loss of adherence is produced by osmolar agents, inducers of cAMP, and colchicine. Phagocytosis of latex particles by rabbit alveolar macrophages in suspension is also transiently decreased by ethanol. These results suggest that inhibition of alveolar macrophage adherence and phagocytosis may be mediated by one or a combination of three mechanisms: osmolar forces altering the cell membrane, changes in cyctic nucleotide concentrations, or disruption of microtubules. Ethanol may act through some combination of these mechanisms to produce functional abnormalities of alveolar macrophages.

Two cases of asymptomatic cryptococcal meningitis are described. The disease was diagnosed only after Cryptococcus neoformans was cultured from lung tissue and urine. These cases represent 2 of 11 meningitis cases seen in a 10-yr period at this hospital. Of 11 cases of extraneural cryptococcosis, 6 had lumbar punctures and these 2 had positive culture results. Asymptomatic cryptococcal meningitis is not rare. Our experience suggested that lumbar punctures should be performed routinely in patients with cultures yielding Cryptococcus neoformans from extraneural sites.

Pneumococcal bacteremia is associated with a high morbidity and mortality, especially when leukopenia is present. To define further the possible factors associated with death in pneumococcal bacteremia, we reviewed all cases at 2 hospitals over a 1-yr period. Overall, increased mortality was associated with women (p = 0.009), nosocomial acquisition of the disease (p = 0.001), the presence of leukopenia (p = 0.00002) or thrombocytopenia (p = 0.025), shock (p = 4 X 10(-8)), and adult respiratory distress syndrome (p = 2 X 10(-7)). Leukopenic and nonleukopenic patients were compared further to ascertain factors that may predispose to leukopenia. Alcoholism was the only associated condition correlating with the presence of leukopenia (p = 0.036), and alcoholism and leukopenia occurred in a group of younger men. We conclude that the association of alcoholism, leukopenia, and pneumococcal sepsis is a distinct clinical entity seen in younger patients and is associated with a very high mortality.

Since the introduction of penicillin in 1942, there have been only 11 culture-proven cases of gonococcal endocarditis in the English literature. Most patients are under 30 years of age and have no history of heart disease. The aortic valve is often involved and aortic regurgitation is common. The bacteriologic diagnosis can be difficult and may require more than six blood cultures and a long incubation period. Circulating immune complexes appear to be the cause of many of the extracardiac manifestations. The three new cases reported herein and review of the literature emphasize the distinctive features of gonococcal endocarditis.

The emphasis of immunization programs and schedules has traditionally been directed to infants and children, since most of the vaccine-preventable diseases are seen predominantly in these age groups. Immunization procedures in adults are less well defined but still of importance. Diseases for which immunizations are given before disease exposure include tetanus, diphtheria, influenza, rubella, and mumps; travelers to foreign countries may need immunizations against typhoid, cholera, yellow fever, typhus, poliomyelitis, plague, and viral hepatitis; other vaccines are available before disease exposure in unusual epidemiologic situations. After exposure to disease but before onset of symptoms, immunizations are available for rabies, viral hepatitis, and measles. After the onset of clinical illness, passive immunization should be given for tetanus, diphtheria, and botulism. This paper summarizes current practices for active and passive immunization against these diseases in adults.

The peritoneovenous shunt has been recently advocated to relieve massive ascites refractory to medical therapy. Several complications of the shunt have been described but the incidence of infection has not been elucidated. We reviewed the records of all patients undergoing peritoneovenous shunt at the Emory University Affiliated Hospitals from 1975 to 1980. Eighty-five peritoneovenous shunts were done in 56 patients. Eighteen of the shunt insertions (21%) were followed by a major infection--eight bacteremias, eight peritonitis, and nine wound infections. Most infections were caused by aerobic gram-negative bacilli or Staphylococcus aureus. Fever was common (62%) in the immediate postoperative period but was not clearly related to infection, or the administration of antibiotics or antipyretics. Shunt removal appeared to be necessary in treating bacteremic patients but not in patients with only peritonitis or wound infections. Infection is a common complication of the peritoneovenous shunt and may limit its usefulness.

Several defects in host defense mechanisms of alcoholics have been described, but their role in the development of infections, especially pneumonia, is uncertain. Ethanol, in concentrations of 400 mg/100 ml, inhibits phagocytosis of radiolabeled bacteria by rabbit alveolar macrophages from 73 to 80% of control. Intracellular survival of Staphylococcus aureus is increased to 131% of control by exposure to ethanol. To evaluate the mechanisms of these ethanol-induced defects, the effect of ethanol on microtubular function and changes in levels of cAMP were evaluated. Colchicine (10(-6) M), a disrupter of microtubules, produces 49% capped cells (migration of fluorescein isothiocyanate-labeled concanavalin A (FITC-ConA) to one end of the cell), but ethanol produces no capping, even at concentrations of 2000 mg/100 ml. This suggests that the ethanol effect is not mediated by disruption of microtubules. cAMP levels, measured by radioimmunoassay, increased two-fold over control values after 10 min incubation with ethanol. The increase is dose dependent with a rapid onset. The effect of ethanol on alveolar macrophages is probably complex, but changes in osmolarity and increases in cAMP levels, perhaps interrelated by some pertubation in the cell membrane, may explain the defect.

During a 36-month period, 28 patients treated for infections due to amikacin-susceptible Pseudomonas aeruginosa subsequently developed infections or colonization with amikacin-resistant P aeruginosa at the same site. Eleven amikacin-susceptible/-resistant pairs of isolates were analyzed for aminoglycoside-inactivating enzymes, plasmid profiles, cellular proteins, outer membrane proteins (OMPs), lipopolysaccharide (LPS) profiles, and amikacin uptake. While clearly distinct from isolates of other patients, sensitive and resistant isolates from the same patients were indistinguishable in plasmid profile, LPS profiles, and OMPs. These results suggest that the resistant P aeruginosa isolates were derived from the sensitive isolates. None of the resistant isolates produced enzymes known to inactivate amikacin. In nine of 11 resistant isolates tested, transport of amikacin into P aeruginosa was reduced. A major mechanism of in vivo development of amikacin resistance in P aeruginosa is alteration in permeability to amikacin, but the aquisition of plasmids or changes in OMPs or LPS profile may not account for this phenomenon.