Treatment of Community-Acquired Pneumonia in Immunocompromised Adults: A Consensus Statement Regarding Initial Strategies.

BACKGROUND: Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. RESEARCH QUESTION: There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. STUDY DESIGN AND METHODS: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. RESULTS: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. INTERPRETATION: This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

Antibiotic Treatment Failure and Associated Outcomes Among Adult Patients With Community-Acquired Pneumonia in the Outpatient Setting: A Real-world US Insurance Claims Database Study.

BACKGROUND: Antibiotic treatment failure is common among patients with community-acquired pneumonia (CAP) who are managed in the outpatient setting and is associated with higher mortality and increased health care costs. This study's objectives were to quantify the occurrence of antibiotic treatment failure (ATF) and to evaluate clinical and economic outcomes between CAP patients who experienced ATF relative to those who did not. METHODS: Retrospective analysis of the MarketScan Commercial & Medicare Supplemental Databases was performed, identifying patients ≥18 years old, with a pneumonia diagnosis in the outpatient setting, and who received a fluoroquinolone, macrolides, beta-lactam, or tetracycline. ATF was defined as any of the following events within 30 days of initial antibiotic: antibiotic refill, antibiotic switch, emergency room visit, or hospitalization. Outcomes included 30-day all-cause mortality and CAP-related health care costs. RESULTS: During the study period, 251 947 unique patients met inclusion criteria. The mean age was 52.2 years, and 47.7% were male. The majority of patients received a fluoroquinolone (44.4%) or macrolide (43.6%). Overall, 22.1% were classified as ATFs. Among 18-64-year-old patients, 21.2% experienced treatment failure, compared with 25.7% in those >65 years old. All-cause mortality was greater in the antibiotic failure group relative to the non-antibiotic failure group (18.1% vs 4.6%, respectively), and the differences in 30-day mortality between antibiotic failure groups increased as a function of age. Mean 30-day CAP-related health care costs were also higher in the patients who experienced treatment failure relative to those who did not ($2140 vs $54, respectively). CONCLUSIONS: Treatment failure and poor outcomes from outpatient CAP are common with current guideline-concordant CAP therapies. Improvements in clinical management programs and therapeutic options are needed.

Behavioral intervention improves treatment outcomes among HIV-infected individuals who have delayed, declined, or discontinued antiretroviral therapy: a randomized controlled trial of a novel intervention.

Nationally up to 60 % of persons living with HIV are neither taking antiretroviral therapy (ART) nor well engaged in HIV care, mainly racial/ethnic minorities. This study examined a new culturally targeted multi-component intervention to address emotional, attitudinal, and social/structural barriers to ART initiation and HIV care. Participants (N = 95) were African American/Black and Latino adults with CD4 < 500 cells/mm(3) not taking ART, randomized 1:1 to intervention or control arms, the latter receiving treatment as usual. Primary endpoints were adherence, evaluated via ART concentrations in hair samples, and HIV viral load suppression. The intervention was feasible and acceptable. Eight months post-baseline, intervention participants tended to be more likely to evidence "good" (that is, 7 days/week) adherence (60 vs. 26.7 %; p = 0.087; OR = 3.95), and had lower viral load levels than controls (t(22) = 2.29, p = 0.032; OR = 5.20), both large effect sizes. This highly promising intervention merits further study.

HIV-Infected Individuals Who Delay, Decline, or Discontinue Antiretroviral Therapy: Comparing Clinic- and Peer-Recruited Cohorts.

A substantial proportion of persons living with HIV/AIDS (PLHA) delay, decline, or discontinue antiretroviral therapy (ART) when it is medically indicated (40-45%), largely African-Americans and Latinos/Hispanics. This study explores the feasibility of locating PLHA, who are not on ART (PLHA-NOA) through clinics and peer-referral; compares the two cohorts on multi-level barriers to ART; and examines readiness to initiate/reinitiate ART, a predictor of treatment outcomes. We recruited adult HIV-infected African-American and Latino/Hispanic PLHA-NOA through HIV hospital clinics and peer-referral in 2012-2013. Participants were engaged in structured 1-h assessments with reliable/valid measures on barriers to ART. We found that recruitment through peers (63.2%, 60/95) was more feasible than in clinics (36.8%, 35/90). Participants were 48.0 years old and had lived with HIV for 14.7 years on average, and 56.8% had taken ART previously. Most (61.1%) were male and African-American (76.8%), and 23.2% were Latino/Hispanic. Peer-recruited participants were older, had lived with HIV longer, were less engaged in HIV care, and were more likely to have taken ART previously. The cohorts differed in reasons for discontinuing ART. Levels of ART knowledge were comparable between cohorts (68.5% correct), and there were no differences in attitudes toward ART (e.g., mistrust), which were in the neutral range. In bivariate linear regression, readiness for ART was negatively associated with physician mistrust (B = -10.4) and positively associated with self-efficacy (B = 5.5), positive outcome expectancies (B = 6.3), beliefs about personal necessity of ART (B = 17.5), and positive internal norms (B = 7.9). This study demonstrates the feasibility of engaging this vulnerable population through peer-referral. Peer-recruited PLHA evidence particularly high rates of risk factors compared to those in hospital clinics. Interventions to support ART initiation and continuation are sorely needed for both subgroups.

ACT2 peer-driven intervention increases enrollment into HIV/AIDS medical studies among African Americans/Blacks and Hispanics: A cluster randomized controlled trial.

African American/Black and Hispanic persons living with HIV/AIDS ("AABH-PLHA") are under-represented in HIV/AIDS medical studies (HAMS). This paper evaluates the efficacy of a social/behavioral intervention to increase rates of screening for and enrollment into HAMS in these populations. Participants (N = 540) were enrolled into a cluster randomized controlled trial of an intervention designed to overcome multi-level barriers to HAMS. Primary endpoints were rates of screening for and enrollment into therapeutic/treatment-oriented and observational studies. Intervention arm participants were 30 times more likely to be screened than controls (49.3 % vs. 3.7 %; p < .001). Half (55.5 %) of those screened were eligible for HAMS, primarily observational studies. Nine out of ten found eligible enrolled (91.7 %), almost all into observational studies (95.2 %), compared to no enrollments among controls. Achieving appropriate representation of AABH-PLHA in HAMS necessitates modification of study inclusion criteria to increase the proportion found eligible for therapeutic HAMS, in addition to social/behavioral interventions.

Kikuchi-Fujimoto disease and acute appendicitis.

A 29-year-old Japanese man developed fever, nausea, vomiting, diarrhoea, right lower quadrant abdominal pain and rebound tenderness. With the clinical suspicion of appendicitis, an abdominal CT scan was performed, which revealed mesenteric lymphadenitis. The patient was hospitalised and treated with antibiotics, but was ultimately found to have Kikuchi-Fujimoto disease (KFD). This diagnosis was facilitated by the use of positron emission tomography scan that identified an accessible inguinal lymph node for biopsy and histopathological evaluation. Invasive abdominal surgery was thereby averted and the patient made a complete recovery on subsequent follow-up. Review of the published literature reveals that pseudoappendicitis due to KFD is a rare occurrence that has generally required abdominal surgery to establish the diagnosis, thus supporting the potential value of the approach taken here.

Fluoroquinolone- and ceftriaxone-based therapy of community-acquired pneumonia in hospitalized patients: the risk of subsequent isolation of multidrug-resistant organisms.

A retrospective cohort study was performed on 175 adult patients treated for community-acquired pneumonia with moxifloxacin or ceftriaxone/azithromycin in a nonintensive care unit. Both cohorts were very similar with regard to a wide range of characteristics including age, severity of disease, comorbidities, length of stay, and mortality. Multidrug-resistant organisms were subsequently isolated from 6 (15%) moxifloxacin-treated patients and 5 (4%) ceftriaxone/azithromycin-treated patients within 90 days after beginning of therapy (P = .026 on logistic regression analysis).

Minorities remain underrepresented in HIV/AIDS research despite access to clinical trials.

BACKGROUND AND OBJECTIVE: The reasons for minority underrepresentation in HIV/AIDS clinical trials remain unclear. We aimed to evaluate the knowledge, experience, and factors that influence minority participation in HIV/AIDS studies in the United States. METHODS: An anonymous, bilingual, self-administered survey on study participation was given to HIV-infected adults attending AIDS Clinical Trials Group-affiliated clinics in the United States and Puerto Rico. Chi-square tests were used to evaluate differences by race, first language, and level of education. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for factors associated with being talked to about participation in a study. RESULTS: We analyzed 2,175 complete surveys (221 in Spanish). Among respondents, 31% were White, 40% were Black/African American (AA), and 21% were Hispanic. The overall rate of previous participation in any HIV/AIDS study was 48%. Hispanics were less likely to know about studies compared to Whites and AAs (67% vs 74% and 76%, respectively; P < .001). Compared to Whites, AAs and Hispanics were less likely to have been talked to about participating in a study (76% vs 67% and 67%, respectively; P < .001). The OR for being talked to about participating in a study was 0.65 (95% CI, 0.52-0.81) for AAs and 0.65 (95% CI, 0.49-0.85) for Hispanics, compared to Whites. AAs and Hispanics were more likely to state that studies were not friendly to their race (17% and 10% vs 4%; P < .001). CONCLUSIONS: Minorities continue to face barriers for HIV/AIDS trial participation, even when clinical research is available. Enrollment strategies should better target minorities to improve recruitment in HIV/AIDS research.

Nested case-control study of the emergence of tigecycline resistance in multidrug-resistant Klebsiella pneumoniae.

We performed a nested case-control study (ratio of 1:4) on the emergence of tigecycline-resistant multidrug-resistant Klebsiella pneumoniae (TR-MDRKP) isolates among patients who initially presented with a tigecycline-susceptible MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95% confidence interval [CI], 1.80 to 14.23; P = 0.002) was the only independent predictor of subsequent isolation of a TR strain.

The association of cytopenias and weight loss with hepatitis C virus virologic response in HIV/HCV-coinfected patients treated with PEG-IFN and RBV.

BACKGROUND: Pegylated interferon (PEG-IFN)/ribavirin (RBV)-related cytopenias have been associated with improved virological outcomes among hepatitis C virus (HCV)-monoinfected patients. This analysis evaluated PEG-IFN/RBV-related cytopenias with virological responses among HIV/HCV-coinfected patients. METHODS: Pooled data from PARADIGM and AIDS Pegasys Ribavirin International CO-infection Trial (APRICOT) trials of HIV/HCV-infected patients treated with PEG-IFN/RBV. Virologic response was categorized as HCV RNA detectable (end of treatment nonresponders [ET-NR]) or nondetectable (end of treatment responders [ETR]). Declines in hemoglobin (Hgb), platelets, neutrophils, lymphocytes, and weight between the groups were compared via analysis of covariance and Cochran-Mantel-Haenszel test. RESULTS: A total of 474 patients, 291 ET-NR and 183 ETR (67 relapsers, 116 with sustained virologic response), 81% male, 52% Caucasian, 88% noncirrhotic, and 67% nondetectable HIV. The ETR experienced greater Hgb declines (≥3.0 g/dL) from baseline (73.8% versus 55.0%; P < .0001), neutrophils ≤1 and ≤ 0.5 × 10(9)/L (66.1% versus 56.4%; P = .0334 and 42.6% versus 33.3%; P = .0312, respectively), and lymphocytes ≤1.5 and ≤0.5 × 10(9)/L (99.5% versus 87.6%; P < .0001 and 24.6% versus 14.9%; P =.0079, respectively). CONCLUSIONS: The HIV/HCV-coinfected patients with ETR experienced greater declines in Hgb, neutrophils, and lymphocytes than the ET-NR patients.

Catfish spine envenomation and bacterial abscess with Proteus and Morganella: a case report.

INTRODUCTION: Abscess formation and cellulitis in the setting of envenomation are rare complications of handling catfish. To the best of our knowledge, isolation of Proteus vulgaris has not been previously recorded, and recovery of Morganella morganii has been reported in only one prior case from wound cultures in patients injured by catfish stings. We report a case of catfish envenomation characterized by abscess formation and cellulitis, in which wound cultures grew these unusual organisms. CASE PRESENTATION: A 52-year-old Chinese-American man was hospitalized with erythema and swelling of his right arm of 10 days' duration after skin penetration by a catfish barb. An abscess of his right thumb had undergone incision and drainage, with purulent drainage sent for wound culture immediately prior to admission. Laboratory studies revealed elevated white blood count, sedimentation rate, and C-reactive protein. The patient was treated with intravenous ampicillin-sulbactam and vancomycin during his hospitalization, and symptoms improved. Wound cultures obtained prior to presentation grew many Proteus vulgaris and Morganella morganii. He was subsequently discharged on a 10-day course of oral ciprofloxacin and amoxicillin-clavulanate. At a 12-month telephone follow-up, the patient denied developing further symptoms and reported that the wound had healed completely without complication. CONCLUSION: Although envenomation and secondary infection are not uncommon sequelae of handling catfish, the present case is unique by virtue of the infecting organisms isolated. Given the prevalence of injury from catfish stings, a review of the literature is presented in order to provide recommendations for prevention and treatment of catfish envenomation.

Does empirical therapy with a fluoroquinolone or the combination of a ß-lactam plus a macrolide result in better outcomes for patients admitted to the general ward?

Community-acquired pneumonia (CAP) is a frequent cause of morbidity and mortality in the United States and worldwide, in particular among older patients and those with significant comorbid conditions. Current guidelines recommend therapy with a fluoroquinolone or a ß-lactam plus a macrolide for the treatment of hospitalized adults with CAP who do not require admission to an intensive care unit. This article provides a brief summary and overview of the existing literature on this topic categorized by the main results; the potential implications for future clinical practice and research are discussed.

Predictors of screening for AIDS clinical trials among African-Americans and Latino/Hispanics enrolled in an efficacious peer-driven intervention: uncovering socio-demographic, health, and substance use-related factors that promote or impede screening.

African-American and Latino/Hispanic persons living with HIV/AIDS are underrepresented in AIDS clinical trials (ACTs). The aim of this paper was to uncover factors, either unmodifiable or not directly targeted for change, that predicted screening for ACTs during an efficacious peer-driven intervention (N = 540 total; N = 351 in an intervention arm, N = 189 control). This paper focused on participants assigned to an intervention arm, 56 % of whom were screened for ACTs. We found a decreased odds of screening was associated with closer proximity to the screening site, gay/lesbian orientation, lower mental health symptoms, current injection drug use, more recent HIV diagnosis, lack of prior screening experience, and failure to attend all intervention sessions, but there were no gender or racial/ethnic differences. Efforts to reduce racial/ethnic disparities in ACTs can be enhanced by attending to these specific factors, which may interfere with programmatic efforts to increase African-American and Latino/Hispanic representation in ACTs.

Maraviroc once-daily nucleoside analog-sparing regimen in treatment-naive patients: randomized, open-label pilot study.

OBJECTIVE: This study was performed to evaluate a once-daily dual-therapy regimen, maraviroc (MVC) + atazanavir/ritonavir (ATV/r), in treatment-naive patients. DESIGN: A phase 2b, randomized, open-label pilot study. METHODS: In Study A4001078 (NCT00827112), treatment-naive patients with CCR5-tropic HIV-1 (HIV-1 RNA ≥1000 copies/mL; CD4 cell count ≥100 cells/mm) were randomized to receive either MVC 150 mg once daily (n = 60) or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily (n = 61) + ATV/r 300/100 mg once daily. Primary endpoint was proportion of patients with HIV-1 RNA <50 copies per milliliter at week 48. RESULTS: At week 48, 44 (74.6%) and 51 (83.6%) patients in the MVC and TDF/FTC treatment groups, respectively, had plasma HIV-1 RNA <50 copies per milliliter. Median change from baseline in CD4 cell count at week 48 was +173 and +187 cells per cubic millimeter with MVC and TDF/FTC, respectively. Seven patients discontinued from each arm; there were no deaths. The incidence of serious adverse events (AEs) was similar in each group; however, there were more grade 3/4 AEs in the MVC group (18 vs 11), mostly due to hyperbilirubinemia. Three patients in each arm were evaluable for virological analysis at discontinuation or failure (HIV-1 RNA >500 copies/mL); no genotypic resistance, change in tropism, or loss of susceptibility relevant to treatment was observed. CONCLUSIONS: The virological activity and immunological benefit of once-daily MVC + ATV/r were confirmed. Indirect hyperbilirubinemia and associated signs were the most commonly reported AEs in both study treatment groups and were not associated with significant transaminase increases. No drug resistance occurred.

Methicillin-susceptible Staphylococcus aureus nasal colonization and the risk of subsequent methicillin-resistant Staphylococcus aureus infections among hospitalized patients.

Few data exist on the risk of methicillin-resistant Staphylococcus aureus (MRSA) infections among known methicillin-susceptible S. aureus (MSSA) carriers. In a cohort of 2991 hospitalized MSSA carriers, 22 (22%) of 98 S. aureus infections that occurred within a subsequent 6-month period were caused by MRSA. Recent fluoroquinolone use was an independent predictor of MRSA infections (P < .001).

The effect of peer-driven intervention on rates of screening for AIDS clinical trials among African Americans and Hispanics.

OBJECTIVES: We examined the efficacy of a peer-driven intervention to increase rates of screening for AIDS clinical trials among African Americans and Hispanics living with HIV/AIDS. METHODS: We used a randomized controlled trial design to examine the efficacy of peer-driven intervention (6 hours of structured sessions and the opportunity to educate 3 peers) compared with a time-matched control intervention. Participants were recruited using respondent-driven sampling (n = 342; 43.9% female; 64.9% African American, 26.6% Hispanic). Most participants (93.3%) completed intervention sessions and 64.9% recruited or educated peers. Baseline and post-baseline interviews (94.4% completed) were computer-assisted. A mixed model was used to examine intervention effects on screening. RESULTS: Screening was much more likely in the peer-driven intervention than in the control arm (adjusted odds ratio [AOR] = 55.0; z = 5.49, P < .001); about half of the participants in the intervention arm (46.0%) were screened compared with 1.6% of controls. The experience of recruiting and educating each peer also increased screening odds among those who were themselves recruited and educated by peers (AOR = 1.4; z = 2.06, P < .05). CONCLUSIONS: Peer-driven intervention was highly efficacious in increasing AIDS clinical trial screening rates among African Americans and Hispanics living with HIV/AIDS.

Increasing and supporting the participation of persons of color living with HIV/AIDS in AIDS clinical trials.

Persons living with HIV/AIDS (PLHA) of color are under-represented in AIDS clinical trials (ACTs), which may limit the generalizability of research findings and denies many individuals access to high levels of care and new treatments available through ACTs. Disproportionately low rates of recruitment in health care settings and by providers are a major barrier to ACTs for this group. Moreover, PLHA of color are more likely than their white peers to decline to participate, mainly due to fear and mistrust (although willingness is also high), negative social norms about ACTs, and difficulty navigating the unfamiliar ACT system. We describe a small number of successful behavioral and structural interventions to increase the participation of PLHA of color in screening for and enrollment into ACTs. HIV care settings, clinical trials sites, and trial sponsors are uniquely positioned to develop procedures, supports, and trials to increase the proportion of PLHA of color in ACTs.

Impact of results of methicillin-resistant Staphylococcus aureus surveillance culture of nasal specimens on subsequent antibiotic prescribing patterns.

We studied the potential impact of results of methicillin-resistant Staphylococcus aureus (MRSA) surveillance culture of nasal specimens on physicians' vancomycin-prescribing habits. We compared 116 case patients who had positive results with 116 matched control subjects who had negative results. On multivariate analyses, a positive MRSA carrier status remained strongly predictive of vancomycin use within the subsequent 12 weeks.

Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial.

BACKGROUND: Dosing frequency is an important determinant of regimen effectiveness. Methods. To compare efficacy of once-daily (QD) versus twice-daily (BID) antiretroviral therapy, we randomized human immunodeficiency virus (HIV)-positive, treatment-naive patients to lopinavir-ritonavir (LPV/r) administered at a dosage of 400 mg of lopinavir and 100 mg of ritonavir BID (n = 160) or 800 mg of lopinavir and 200 mg of ritonavir QD (n = 161), plus either emtricitabine 200 mg QD and extended-release stavudine at a dosage of 100 mg QD or tenofovir at a dosage of 300 mg QD. Randomization was stratified by screening HIV RNA level <100,000 copies/mL versus > or = 100,000 copies/mL. The primary efficacy end point was sustained virologic response (SVR; defined as reaching and maintaining an HIV RNA level <200 copies/mL) through week 48. RESULTS: Subjects were 78% male, 33% Hispanic, and 34% black. A total of 82% of subjects completed the study, and 71% continued to receive the initially assigned dosage schedule. The probability of SVR did not differ significantly for the BID versus QD comparison, with an absolute proportional difference of 0.03 (95% confidence interval [CI], -0.07 to 0.12). The comparison depended on the screening RNA stratum (P=.038); in the higher RNA stratum, the probability of SVR was significantly better in the BID arm than in the QD arm: 0.89 (95% CI, 0.79-0.94) versus 0.76 (95% CI, 0.64-0.84), a difference of 0.13 (95% CI, 0.01-0.25). Lopinavir trough plasma concentrations were higher with BID dosing. Adherence to prescribed doses of LPV/r was 90.6% in the QD arm versus 79.9% in the BID arm (P<.001). Conclusions. Although subjects assigned to QD regimens had better adherence, overall treatment outcomes were similar in the QD and BID arms. Subjects with HIV RNA levels > or =100,000 copies/mL had better SVR with BID regimens at 48 weeks, which suggests a possible advantage in this setting for more frequent dosing. Clinical trial registration. ClinicalTrials.gov registration number: NCT00036452.

The virologic and immunologic effects of cyclosporine as an adjunct to antiretroviral therapy in patients treated during acute and early HIV-1 infection.

Acute human immunodeficiency virus type 1 (HIV-1) infection is characterized by high levels of immune activation. Immunomodulation with cyclosporine combined with antiretroviral therapy (ART) in the setting of acute and early HIV-1 infection has been reported to result in enhanced immune reconstitution. Fifty-four individuals with acute and early infection were randomized to receive ART with 4 weeks of cyclosporine versus ART alone. In 48 subjects who completed the study, there were no significant differences between treatment arms in levels of proviral DNA or CD4(+) T cell counts. Adjunctive therapy with cyclosporine in this setting does not provide apparent virologic or immunologic benefit.