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MMW Fortschritte der Medizin 06/2012; 154(11):47-50.
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MMW Fortschritte der Medizin 06/2012; 154(11):51-2.
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ABSTRACT: Antiretroviral treatment directed against HIV is highly effective, yet limited by drug resistance mutations. We hypothesized that CD8 T cells targeting drug-resistant HIV mutants are able to inhibit viral replication in the setting of a failing therapeutic regimen. We evaluated CD8 T-cell responses and mapped epitopes in HIV-infected patients by interferon-gamma Elispot and intracellular cytokine staining. Autologous virus was sequenced by RT-PCR. Viral replication inhibition assays were performed using M184V mutant virus and CD8 T cell lines. CD8 T-cell responses toward the regions of viral drug resistance mutations in Pol are frequent. Focusing on the M184V mutation, A*02:01-YQYVDDLYV and A*02:01-VIYQYVDDLYV were identified as optimal epitopes for the majority of study subjects. Viral replication of M184V HIV mutants was inhibited by CD8 T cell lines in vitro. In case of a failing lamivudine/emtricitabine containing regimen, individuals with a CD8 T-cell response toward M184V had a significant lower viral load than those without a CD8 response (p = 0.005). Two study subjects even achieved an undetectable viral load. Our data suggest that control of M184V mutant virus by CD8 T-cell responses is possible in vitro and in vivo. This control has important implications for therapeutic vaccination strategies.
Medical Microbiology and Immunology 12/2011; 201(2):201-11. · 3.83 Impact Factor
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MMW Fortschritte der Medizin 09/2011; 153(38):29-31, 33; quiz 34.
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MMW Fortschritte der Medizin 05/2011; 153(19):45-8; quiz 49.
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ABSTRACT: To monitor the mitochondrial transmembrane potential (ΔΨm), peripheral blood mononuclear cells (PBMCs) from 18 HIV-uninfected individuals completing a 4-week course of HIV postexposure prophylaxis (PEP) with emtricitabine/tenofovir and lopinavir/ritonavir were analyzed. ΔΨm was assessed by FACS analysis after staining with JC-1 using a mixed effects regression analysis. Apoptosis was determined by Annexin-V-FITC and propidium iodide staining. ΔΨm decreased significantly during HIV-PEP (p=0.0015 for the linear term, p=0.0039 for the quadratic term of days on PEP) and normalized several weeks after stopping antiretrovirals. The apoptosis rates did not change significantly (p=0.42). Even newer drugs such as tenofovir and emtricitabine may cause side effects due to mitochondrial dysfunction.
AIDS research and human retroviruses 02/2011; 27(9):969-72. · 2.18 Impact Factor
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ABSTRACT: Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV-specific CD8 T cells has not been studied in detail so far in chronic HIV-1 infection. In this study, the expression of markers of positive (CD38) and negative (PD-1) immune signals on virus-specific CD8 T cells in chronic, untreated HIV-1 infection was evaluated using intracellular cytokine staining. Viral escape mutations were assessed by autologous virus sequence analysis and subsequent peptide titration assays. Single-epitope CD8 T-cell responses toward Gag, Pol, and Nef were compared in 12 HIV-1 controllers (viral load <5,000 cp/ml) and 12 HIV-1 progressors (viral load >50,000 cp/ml) and a highly significant increase of CD38/PD-1 co-expression on virus-specific CD8 T cells in progressors was found (P < 0.0001). The level of CD38/PD-1 co-expression was independent of epitope specificity. Longitudinal follow-up revealed a clear drop in CD38/PD-1 co-expression on virus-specific CD8 T cells after the suppression of antigen following either viral escape mutation or the initiation of HAART (P = 0.004). Antigen persistence with a fluctuating viral load revealed stable levels of CD38/PD-1 co-expression whereas significant rises in viral load were accompanied or even preceded by substantial increases in CD38/PD-1 co-expression. The CD38/PD-1 phenotype clearly distinguishes HIV-specific CD8 T-cell responses between controllers and progressors. Whether it plays a causative role in disease progression remains debatable. J. Med. Virol. 82:358-370, 2010. (c) 2010 Wiley-Liss, Inc.
Journal of Medical Virology 03/2010; 82(3):358-70. · 2.82 Impact Factor
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Robert P Gaynes,
Carolyn V Gould,
Jonathan Edwards,
Theresa L Antoine,
Henry M Blumberg,
Kathryn Desilva,
Mark King,
Alice Kraman,
Jan Pack,
Bruce Ribner, Ulrich Seybold,
James Steinberg,
John A Jernigan
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ABSTRACT: We examined interventions to optimize piperacillin-tazobactam use at 4 hospitals. Interventions for rotating house staff did not affect use. We could target empiric therapy in only 35% of cases. Because prescribing practices seemed to be institution specific, interventions should address attitudes of local prescribers. Interventions should target empiric therapy and ordering of appropriate cultures.
Infection Control and Hospital Epidemiology 07/2009; 30(8):794-6. · 3.67 Impact Factor
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ABSTRACT: A new generation of diagnostic tests, the interferon-gamma release assays (IGRAs), have been developed for the detection of latent tuberculosis infection (LTBI). Limited data are available on their use in HIV-infected persons.
A cross-sectional study was carried out at 2 HIV clinics in Atlanta to assess the utility of two IGRA tests (T-SPOT.TB [TSPOT] and QuantiFERON-TB Gold in Tube [QFT-3G]) compared to the tuberculin skin test (TST).
336 HIV-infected persons were enrolled. Median CD4 count was 335 cells/microl and median HIV viral load was 400 copies/ml. Overall, 27 patients (8.0%) had at least 1 positive diagnostic test for LTBI: 7 (2.1%) had a positive TST; 9 (2.7%) a positive QFT-3G; and 14 (4.2%) a positive TSPOT. Agreement between the 3 diagnostic tests was poor: TST and TSPOT, [kappa = 0.16, 95% CI (-0.06, 0.39)], TST and QFT-3G [kappa = 0.23, 95% CI (-0.05, 0.51)], QFT-3G and TSPOT [kappa = 0.06, 95% CI (-0.1, 0.2)]. An indeterminate test result occurred among 6 (1.8%) of QFT-3G and 47 (14%) of TSPOT tests. In multivariate analysis, patients with a CD4 < or = 200 cells/microl were significantly more likely to have an indeterminate result [OR = 3.6, 95% CI (1.9, 6.8)].
We found a low prevalence of LTBI and poor concordance between all 3 diagnostic tests. Indeterminate test results were more likely at CD4 counts < or = 200 cells/microl. Additional studies among HIV-infected populations with a high prevalence of TB are needed to further assess the utility of IGRAs in this patient population.
BMC Infectious Diseases 02/2009; 9:15. · 3.12 Impact Factor
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ABSTRACT: The goal of this study was to define more clearly the impact of community-acquired methicillin-resistant Staphylococcus aureus clones (eg, USA300 and USA400) on colonization and infection in infants in intensive care nurseries and potential modes of transmission of community-acquired methicillin-resistant S aureus clones.
Prospective surveillance for methicillin-resistant S aureus colonization and infection was performed among infants in the intensive care nurseries at Grady Memorial Hospital (Atlanta, GA) between 1993 and 2006. Beginning in September 2004, nares surveillance cultures were collected at admission. Methicillin-resistant S aureus isolates were genotyped by using pulsed-field gel electrophoresis and multiplex polymerase chain reaction assays for staphylococcal chromosomal cassette mec gene complex type and Panton-Valentine leukocidin genes. Prevalence of and risk factors for colonization with community-acquired versus health care-associated methicillin-resistant S aureus clones (eg, USA100) were assessed.
Between 1993 and 2006, 130 (3.5%) of 3707 infants were identified to be colonized with methicillin-resistant S aureus. Twelve (1.2%) of 996 admission nares cultures were positive for methicillin-resistant S aureus (since initiation of admission cultures in September 2004). Community-acquired methicillin-resistant S aureus clones were first recovered in 1998; the proportion of methicillin-resistant S aureus clones of community origin increased significantly between 1998 and 2004. Multivariate analysis identified vaginal delivery and maternal smoking, both among infants of mothers receiving systemic antibiotic treatment before delivery, as independent predictors for neonatal colonization with community-acquired methicillin-resistant S aureus. Systemic antibiotic therapy before delivery for nonsmoking mothers delivering through cesarean section and possibly endotracheal intubation were associated with the recovery of health care-associated methicillin-resistant S aureus clones.
Community-acquired methicillin-resistant S aureus clones have emerged as a major cause of methicillin-resistant S aureus colonization in high-risk newborns. Community-acquired methicillin-resistant S aureus recovery was associated with acquisition during birth, whereas health care-associated methicillin-resistant S aureus clones seemed to be transmitted nosocomially.
PEDIATRICS 12/2008; 122(5):1039-46. · 4.47 Impact Factor
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ABSTRACT: Nasal S. aureus colonization was detected in 62/127 patients (49%) at a German infectious diseases clinic; MRSA colonization was infrequent at 2.4%. Male gender (OR=2.71, p=0.04), antimicrobial therapy in hospitalized patients (OR=20.1, p=0.02), and HIV infection in patients>42 y of age (OR=7.74, p=0.02) were independent risk factors for S. aureus colonization.
Scandinavian Journal of Infectious Diseases 10/2008; 41(1):63-6. · 1.72 Impact Factor
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ABSTRACT: After Hurricane Katrina, 50 patients were evacuated to Grady Memorial Hospital in Atlanta, Georgia, with limited medical records. The infection control department ordered contact precautions for 16 patients. Surveillance cultures performed on admission identified colonization with multidrug-resistant (MDR) bacteria in 9 patients (18%). Presence of a wound was the strongest predictor for MDR colonization. More data are needed to reliably predict MDR bacterial colonization.
Infection Control and Hospital Epidemiology 07/2007; 28(6):726-9. · 3.67 Impact Factor
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Clinical Infectious Diseases 03/2007; 44(4):502-5. · 9.15 Impact Factor
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Theresa L Antoine,
Amy B Curtis,
Henry M Blumberg,
Kathryn Desilva,
Mesfin Fransua,
Carolyn V Gould,
Mark King,
Alice A Kraman,
Jan Pack,
Bruce Ribner, Ulrich Seybold,
James P Steinberg,
Jane B Wells,
Ronda L Sinkowitz-Cochran,
Denise Cardo,
John A Jernigan,
Robert P Gaynes
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ABSTRACT: We investigated knowledge, attitudes, and behaviors of prescribers concerning piperacillin-tazobactam use at 4 Emory University-affiliated hospitals. Discussions during focus groups indicated that the participants' perceived knowledge of clinical criteria for appropriate piperacillin-tazobactam use was inadequate. Retrospective review of medical records identified inappropriate practices. These findings have influenced ongoing interventions aimed at optimizing piperacillin-tazobactam use.
Infection Control and Hospital Epidemiology 12/2006; 27(11):1274-7. · 3.67 Impact Factor
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ABSTRACT: Whether community-associated methicillin-resistant Staphylococcus aureus (MRSA) genotypes (e.g., USA300) are a major cause of bloodstream infections (BSIs) and health care-associated infections has been poorly defined.
Consecutive MRSA isolates recovered from patients with BSIs were prospectively collected at an urban public hospital. Molecular typing studies were performed. Prevalence and risk factors for the MRSA USA300 genotype were assessed.
One hundred thirty-two cases of MRSA BSI were documented over 7.5 months in 2004 (incidence, 6.79 per 1000 admissions); 116 isolates were available for genotyping. Characteristics of the 116 evaluable cases included: a mean age 47 years; 62% were male, 82% were African American, and 22% were HIV seropositive. The crude in-hospital mortality rate was 22%. In 107 cases (92%), there was contact with a health care facility within the year prior to infection, and a nosocomial infection (defined as positive blood culture results obtained >48 h after admission) occurred in 49 cases (42%). PFGE demonstrated that 39 (34%) of the 116 isolates were the MRSA USA300 genotype; 34 (29%) were USA100; 42 (36%) were USA500; and 1 (1%) was USA800. MRSA USA300 accounted for 28% of health care-associated BSIs and 20% of nosocomial MRSA BSIs. In multivariate analysis, isolation of the USA300 genotype was associated with injectiondrug use (OR, 3.67; 95% CI, 1.10-12.28) and skin and soft tissue infection (OR, 4.26; 95% CI, 1.08-16.84). Patients who resided in long-term care facilities (OR, 0.09; 95% CI, 0.01-0.82) and those who were treated with antimicrobials in the prior year were less likely to have MRSA USA300 genotype recovered (OR, 0.10; 95% CI, 0.02-0.49).
MRSA USA300 genotype, the predominant cause of community-associated MRSA infections in our area (Atlanta, GA), has now emerged as a significant cause of health care-associated and nosocomial BSI. MRSA USA300 as a nosocomial pathogen presents new challenges to infection control programs.
Clinical Infectious Diseases 03/2006; 42(5):647-56. · 9.15 Impact Factor
