Eric Chamot

Effectiveness of Combination Antimicrobial Therapy for Pseudomonas aeruginosa Bacteremia

ABSTRACT It remains controversial whether combination therapy, given empirically or as definitive treatment, for Pseudomonas aeruginosa bacteremia is associated with a better outcome than monotherapy. The aim of the present study was to compare the rates of survival among patients who received either combination therapy or monotherapy for P. aeruginosa bacteremia. We assembled a historical cohort of 115 episodes of P. aeruginosa bacteremia treated with empirical antipseudomonal therapy between 1988 and 1998. On the basis of susceptibility testing of the bacteremic P. aeruginosa isolate, we defined categories of empirical treatment, including adequate combination therapy, adequate monotherapy, and inadequate therapy, as well as corresponding categories of definitive therapy. Neither the adequacy of the empirical treatment nor the use of combination therapy predicted survival until receipt of the antibiogram. However, the risk of death from the date of receipt of the antibiogram to day 30 was higher for both adequate empirical monotherapy (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.0 to 14.1) and inadequate empirical therapy (aHR, 5.0; 95% CI, 1.2 to 20.4) than for adequate empirical combination therapy. Compared to adequate definitive combination therapy, the risk of death at 30 days was also higher with inadequate definitive therapy (aHR, 2.6; 95% CI, 1.1 to 6.7) but not with adequate definitive monotherapy (aHR, 0.70; 95% CI, 0.30 to 1.7). In this retrospective analysis the use of adequate combination antimicrobial therapy as empirical treatment until receipt of the antibiogram was associated with a better rate of survival at 30 days than the use of monotherapy. However, adequate combination antimicrobial therapy given as definitive treatment for P. aeruginosa bacteremia did not improve the rate of survival compared to that from the provision of adequate definitive monotherapy.

Nonresponse bias in a survey of patient perceptions of hospital care.

Background:Incomplete participation is of particular concern for surveys of patient perceptions of care because patients who have negative opinions may be least likely to participate. Objective:We sought to examine indirect evidence of nonresponse bias. Design:We re-analyzed data from a cross-sectional patient survey. Subjects:Our subjects were patients discharged from a Swiss hospital (n = 2156). Measures:We measured the following: (1) an observed problem score, based on 15 key items of the Picker Patient Experience questionnaire, (2) a predicted problem score, and (3) a participation propensity score. The latter scores were computed for all eligible patients, including those who did not return the survey, from routinely available baseline data. Results:The participation rate was 70% (n = 1518), and the mean problem score was 29.9 (SD 23.8). Early respondents reported significantly fewer problems than late respondents (28.6 versus 32.9, P = 0.001). Participation propensity scores were progressively lower in early respondents (mean 74.2), late respondents (70.7), and nonrespondents (63.9, P < 0.001); the pattern was similar for predicted problem scores (early respondents: 29.5; late respondents: 30.5; nonrespondents: 33.4, P < 0.001). The propensity to participate was negatively associated with the problem score (Pearson r = −0.19). Finally, predictors of participation were similar to predictors of problem scores. Conclusions:The tendency to participate in the survey was negatively associated with the report of problems during hospitalization. Nevertheless, increasing participation from 30% to 70% had only a modest influence on the final conclusions of the survey.

Impact of Small Reductions in Plasma HIV RNA Levels on the Risk of Heterosexual Transmission and Disease Progression

Objective:To estimate the impact of small changes in plasma levels of HIV-1 RNA on the risk of heterosexual transmission or disease progression to an AIDS-defining event or death. Design and methods:We systematically reviewed the published literature for studies that evaluated small viral load changes among antiretroviral-therapy-naive, adult populations. We modeled relative risk estimates for viral transmission and disease progression according to 0.3, 0.5, and 1.0 log10 increments of HIV load. Results:We calculated that the likelihood of transmitting HIV by heterosexual contact increased, on average, by 20% and that the annual risk of progression to an AIDS-defining illness or related death increased by 25% with every 0.3 log10 increment in HIV RNA. A 0.5 log10 increment in HIV RNA was associated with 40% greater risk of heterosexual transmission and 44% increased risk of progression to AIDS or death. A 1.0 log10 increment in HIV RNA was associated with 100% greater risk of heterosexual transmission and 113% increased risk of progression to AIDS or death. Conclusion:Antiretroviral therapy continues to be unavailable or not-yet-indicated for 72% of the worlds HIV-infected persons. Mounting evidence that treatment of coinfections may reduce HIV viral load, even modestly, suggests the priority of improved adjunctive care for HIV-infected persons even without antiretroviral therapy, both to slow disease progression and to reduce infectiousness.

Multimorbidity Patterns in HIV-Infected Patients: The Role of Obesity in Chronic Disease Clustering

Background:Increases in multimorbidity and obesity have been noted in HIV-infected populations in the current treatment era. Patterns of multimorbid disease clustering and the impact of obesity on multimorbidity are understudied in this population. Methods:We examined obesity and multimorbidity patterns among 1844 HIV-infected patients in the UAB 1917 Clinic. Exploratory factor analysis was used to identify the underlying factor structure responsible for clustering. Patterns among the resulting morbidity factors by body mass index (BMI) category were explored. Multivariable logistic regression models were fit to identify predictors of multimorbidity cluster patterns. Results:The prevalence of multimorbidity was 65% (1205/1844). Prevalence increased with progressive BMI categories from underweight (64%) to obese (79%). Three multimorbidity clusters were identified: “metabolic,” including hypertension, gout, diabetes mellitus, and chronic kidney disease (range, 0.41–0.84; P < 0.001); “Behavioral,” including mood disorders, dyslipidemia, chronic obstructive pulmonary disease, chronic ulcer disease, osteoarthritis, obstructive sleep apnea, and cardiac disorders (range, 0.32–0.57; P < 0.001); “Substance Use,” including alcohol abuse, substance abuse, tobacco abuse, and hepatitis C (range, 0.53–0.89; P < 0.001). Obesity was associated with increased odds of multimorbidity (obese vs. normal BMI category: OR = 1.52, 95% CI: 1.15 to 2.00). Conclusions:Three patterns of disease clustering were identified. Obesity was associated with a higher likelihood of multimorbidity. The management of multimorbidity and obesity will need to be addressed in future clinical practice guidelines to enhance long-term outcomes of HIV-infected patients in the current treatment era.

HIV and hepatitis B and C incidence rates in US correctional populations and high risk groups: a systematic review and meta-analysis.

BackgroundHigh Human Immunodeficiency Virus (HIV) prevalence and high risk behaviors have been well documented within United States (US) correctional systems. However, uncertainty remains regarding the extent to which placing people in prison or jail increases their risk of HIV infection, and regarding which inmate populations experience an increased incidence of HIV. Describing these dynamics more clearly is essential to understanding how inmates and former detainees may be a source for further spread of HIV to the general US population.MethodsThe authors conducted a systematic review and meta-analysis of studies describing HIV incidence in US correctional facility residents and, for comparison, in high risk groups for HIV infection, such as non-incarcerated intravenous drug users (IVDU) and men who have sex with men (MSM) in the US. HIV incidence rates were further compared with Hepatitis B and Hepatitis C Virus rates in these same populations.ResultsThirty-six predominantly prospective cohort studies were included. Across all infection outcomes, continuously incarcerated inmates and treatment recruited IVDU showed the lowest incidence, while MSM and street recruited IVDU showed the highest. HIV incidence was highest among inmates released and re-incarcerated. Possible sources of heterogeneity identified among HIV studies were risk population and race.ConclusionsAlthough important literature gaps were found, current evidence suggests that policies and interventions for HIV prevention in correctional populations should prioritize curtailing risk of infection during the post-release period. Future research should evaluate HIV incidence rates in inmate populations, accounting for proportion of high risk sub-groups.

Co-infection with HIV and hepatitis C virus in former plasma/blood donors: challenge for patient care in rural China.

Background:Illegal commercial plasma donation in the late 1980s and early 1990s caused blood-borne infections in China. Objectives:To estimate the prevalence of HIV and hepatitis C virus (HCV) infections and to identify associated risk factors in central China with a history of illegal plasma collection activities. Design and methods:A cross-sectional study was carried out in 2004, in which all adult residents in four villages in rural Shanxi Province were invited for a questionnaire interview and testing of HIV and HCV antibodies. Results:Of 3062 participating villagers, 29.5% reported a history of selling whole blood or plasma. HIV seropositivity was confirmed in 1.3% of subjects and 12.7% were HCV positive. Their co-infection rates were 1.1% among all study subjects, 85% among HIV-positive subjects, and 8.7% among HCV-positive subjects. Selling plasma [odds ratio (OR), 22.5; 95% confidence interval (CI), 16.1–31.7; P < 0.001] or blood (OR, 3.1; 95% CI, 2.3–4.2; P < 0.001) were independently associated with HIV and/or HCV infections. Although a spouses history of selling plasma/blood was not associated with either infection, the HIV or HCV seropositivity of a spouse was significantly associated with HIV and/or HCV infections (both OR, 3.2; 95% CI, 2.0–5.2 in men, 2.0–4.9 in women; P < 0.001). For men, residence in the village with a prior illegal plasma collection center (OR, 2.5; 95% CI, 1.7–3.7; P < 0.001) and for women, older age (OR, 3.4; 95% CI, 1.2–14.0; P = 0.04) were associated with HIV and/or HCV infections. Conclusions:HIV and HCV infections are now prevalent in these Chinese communities. HIV projects should consider screening and care for HCV co-infection.

Partner notification for sexually transmitted infections in developing countries: a systematic review

BackgroundThe feasibility and acceptability of partner notification (PN) for sexually transmitted infections (STIs) in developing countries was assessed through a comprehensive literature review, to help identify future intervention needs.MethodsThe Medline, Embase, and Google Scholar databases were searched to identify studies published between January 1995 and December 2007 on STI PN in developing countries. A systematic review of the research extracted information on: (1) willingness of index patients to notify partners; (2) the proportion of partners notified or referred; (3) client-reported barriers in notifying partners; (4) infrastructure barriers in notifying partners; and (5) PN approaches that were evaluated in developing countries.ResultsOut of 609 screened articles, 39 met our criteria. PN outcome varied widely and was implemented more often for spousal partners than for casual or commercial partners. Reported barriers included sociocultural factors such as stigma, fear of abuse for having an STI, and infrastructural factors related to the limited number of STD clinics, and trained providers and reliable diagnostic methods. Client-oriented counselling was found to be effective in improving partner referral outcomes.ConclusionsSTD clinics can improve PN with client-oriented counselling, which should help clients to overcome perceived barriers. The authors speculate that well-designed PN interventions to evaluate the impact on STI prevalence and incidence along with cost-effectiveness components will motivate policy makers in developing countries to allocate more resources towards STI management.

Randomized controlled trial to improve childhood immunization adherence in rural Pakistan: redesigned immunization card and maternal education

Objective  A substantial dropout from the first dose of diphtheria‐tetanus‐pertussis (DTP1) to the 3rd dose of DTP (DTP3) immunization has been recorded in Pakistan. We conducted a randomized controlled trial to assess the effects of providing a substantially redesigned immunization card, centre‐based education, or both interventions together on DTP3 completion at six rural expanded programme on immunization (EPI) centres in Pakistan.

Association between Vancomycin-Resistant Enterococci Bacteremia and Ceftriaxone Usage

OBJECTIVE Vancomycin-resistant enterococci (VRE) have become a public health concern with implications for patient mortality and costs. Hospital antibiotic usage may impact VRE incidence, but the relationship is poorly understood. Animal investigations suggest that ceftriaxone may be associated with VRE proliferation. We measured antimicrobial usage and VRE bloodstream infection (VRE-BSI) incidence to test our hypothesis that increased ceftriaxone usage would be associated with a higher incidence of VRE-BSI. DESIGN Retrospective cohort study. SETTING University of Alabama at Birmingham Medical Center, a 900-bed urban tertiary care hospital. PARTICIPANTS All patients admitted during the study period contributed data. METHODS We conducted a retrospective analysis of antimicrobial usage and VRE-BSI from 2005 to 2008 (43 months). Antimicrobial usage was quantified as days of therapy (DOTs) per 1,000 patient-days. VRE-BSI incidence was calculated as cases per 1,000 patient-days. Negative binomial regression with adjustment for correlation between consecutive observations was used to measure the association between antimicrobial usage and VRE-BSI incidence at the hospital- and care-unit levels. RESULTS VRE-BSI incidence increased from 0.06 to 0.17 infections per 1,000 patient-days. Hospital VRE-BSI incidence was associated with prior-month ceftriaxone DOTs (incidence rate ratio, 1.38 per 10 DOTs; P = .005). After controlling for ceftriaxone, prior-month cephalosporin usage (class) was not predictive of VRE-BSI (P = .70). Similarly, prior-month usage of piperacillin-tazobactam, ceftazidime, cefepime, cefazolin, or vancomycin was not predictive of VRE-BSI when considered individually (P≥ .4 for all comparisons). The final model suggests that type of intensive care unit was related to VRE-BSI incidence. CONCLUSIONS Ceftriaxone usage in the prior month, but not cephalosporin (class) or vancomycin usage, was related to VRE-BSI incidence. These findings suggest that an antimicrobial stewardship program that limits ceftriaxone may reduce nosocomial VRE-BSI incidence.

Pain is independently associated with impaired physical function in HIV-infected patients.

INTRODUCTION Human immunodeficiency virus (HIV)-infected patients in the current treatment era can achieve normal life expectancies but experience a high degree of medical and psychiatric comorbidity. Impaired physical function and pain, often in the context of mood disorders and substance abuse, are common in HIV-infected patients. The objective of this study was to investigate the relationship of pain, a modifiable condition, to functional impairment in HIV-infected patients, independent of mood disorders and substance abuse. METHODS Participants in a prospective cohort of HIV-infected patients at the University of Alabama at Birmingham were included. Patient-reported outcome measures were used to cross-sectionally assess pain and physical function (EuroQOL), mood disorders (PHQ), and substance abuse (ASSIST). Univariate and multivariable models were built with pain as the principal independent variable of interest and three domains of physical function (mobility, self-care, and usual activities) as outcomes. Covariates included mood, substance abuse, age, race, sex, insurance status, HIV transmission risk factor, and CD4+ T-cell count. RESULTS Among 1,903 participants, 693 (37%) reported pain; 509 (27%) had a mood disorder; and 157 (8.4%) reported current substance abuse. In multivariable models, pain was independently associated with increased odds of impairment in all three domains of physical function investigated-mobility (aOR 10.5, 95% CI 7.6-14.6), self-care (aOR 4.1, 95% CI 2.2-7.4), and usual activities (aOR 5.4, 95% CI 4.0-7.4). DISCUSSION Pain was associated with substantially increased odds of impairment in physical function. Pain should be an important consideration in HIV primary care. Interventions to address pain and impaired physical function should be investigated.