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1.
GMS Infect Dis ; 8: Doc07, 2020.
Article in English | MEDLINE | ID: mdl-32373432

ABSTRACT

This is the thirteenth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Bacterial meningitis is a life-threatening infectious disease with high mortality and disability rates requiring prompt initiation of antimicrobial treatment to lower these rates.

2.
World J Gastroenterol ; 22(16): 4201-10, 2016 Apr 28.
Article in English | MEDLINE | ID: mdl-27122670

ABSTRACT

AIM: To assess the rate of infection, appropriateness of antimicrobial-therapy and mortality on intensive care unit (ICU). Special focus was drawn on patients with liver cirrhosis. METHODS: The study was approved by the local ethical committee. All patients admitted to the Internal Medicine-ICU between April 1, 2007 and December 31, 2009 were included. Data were extracted retrospectively from all patients using patient charts and electronic documentations on infection, microbiological laboratory reports, diagnosis and therapy. Due to the large hepatology department and liver transplantation center, special interest was on the subgroup of patients with liver cirrhosis. The primary statistical-endpoint was the evaluation of the influence of appropriate versus inappropriate antimicrobial-therapy on in-hospital-mortality. RESULTS: Charts of 1979 patients were available. The overall infection-rate was 53%. Multiresistant-bacteria were present in 23% of patients with infection and were associated with increased mortality (P < 0.000001). Patients with infection had significantly increased in-hospital-mortality (34% vs 17%, P < 0.000001). Only 9% of patients with infection received inappropriate initial antimicrobial-therapy, no influence on mortality was observed. Independent risk-factors for in-hospital-mortality were the presence of septic-shock, prior chemotherapy for malignoma and infection with Pseudomonas spp. Infection and mortality-rate among 175 patients with liver-cirrhosis was significantly higher than in patients without liver-cirrhosis. Infection increased mortality 2.24-fold in patients with cirrhosis. Patients with liver cirrhosis were at an increased risk to receive inappropriate initial antimicrobial therapy. CONCLUSION: The results of the present study report the successful implementation of early-goal-directed therapy. Liver cirrhosis patients are at increased risk of infection, mortality and to receive inappropriate therapy. Increasing burden are multiresistant-bacteria.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/mortality , Hospital Mortality , Inappropriate Prescribing , Intensive Care Units , Liver Cirrhosis/mortality , Process Assessment, Health Care , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Drug Resistance, Multiple, Bacterial , Female , Germany , Guideline Adherence , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/therapy , Male , Microbial Sensitivity Tests , Middle Aged , Patient Selection , Practice Guidelines as Topic , Practice Patterns, Physicians' , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
3.
Front Public Health ; 2: 35, 2014.
Article in English | MEDLINE | ID: mdl-24783192

ABSTRACT

OBJECTIVE: Effective response to biological events necessitates ongoing evaluation of preparedness. This study was a bilateral German-Israeli collaboration aimed at developing an evaluation tool for assessing preparedness of medical facilities for biological events. METHODS: Measurable parameters were identified through a literature review for inclusion in the evaluation tool and disseminated to 228 content experts in two modified Delphi cycles. Focus groups were conducted to identify psychosocial needs of the medical teams. Table-top and functional exercises were implemented to review applicability of the tool. RESULTS: One hundred seventeen experts from Germany and Israel participated in the modified Delphi. Out of 188 parameters that were identified, 183 achieved a consensus of >75% of the content experts. Following comments recommended in the Delphi cycles, and feedback from focus groups and hospital exercises, the final tool consisted of 172 parameters. Median level of importance of each parameter was calculated based on ranking recommended in the Delphi process. Computerized web-based software was developed to calculate scores of preparedness for biological events. CONCLUSION: Ongoing evaluation means, such as the tool developed in the study, can facilitate the need for a valid and reliable mechanism that may be widely adopted and implemented as quality assurance measures. The tool is based on measurable parameters and indicators that can effectively present strengths and weaknesses in managing a response to a public health threat, and accordingly, steps can be implemented to improve readiness. Adoption of such a tool is an important component of assuring public health and effective emergency management.

4.
Ther Drug Monit ; 36(2): 192-201, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24632753

ABSTRACT

OBJECTIVE: Lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors is one standard antiretroviral therapy regimen, both in patients with HIV alone and coinfected with hepatitis B or C. Our objective was to investigate whether hepatitis coinfection without clinical signs of hepatic impairment is a cofactor altering lopinavir pharmacokinetics and influencing therapy outcome. METHODS: Steady-state 12-hour pharmacokinetic profiles of lopinavir/ritonavir were assessed in patients with (group 1, n = 20) or without (group 2, n = 36) hepatitis coinfection, taking lopinavir/ritonavir 400/100 mg twice a day plus nucleoside reverse transcriptase inhibitors, measured by means of high-performance liquid chromatography-tandem mass spectrometry. Demographic (sex, age, weight), pharmacological (formulation, comedication), clinical, and virological/immunologic parameters (HIV-RNA PCR, CD4(+) cell count) were compared between the groups and included in regression analyses for correlations with lopinavir pharmacokinetic parameters (C(min), C(max), AUC, CL, and t(1/2)) and viral load evolution over 48 weeks on therapy. Patient pairs were matched 1:2 for the parameters sex, age, weight, ethnicity, and drug formulation. RESULTS: None of the hepatitis-related cofactors (aspartate aminotransferase, alanine aminotransferase, γGT, HBe Ag, HBsAg, HCV-RNA PCR, HCV-therapy) had an influence on lopinavir pharmacokinetics in this group of patients. Lopinavir C(min) (P = 0.039) and area under the curve (P = 0.038) and ritonavir C(max) (P = 0.049) were significantly enhanced in hepatitis-coinfected patients, but correlated only with drug formulation (ie, soft gel capsule or Meltrex tablet formulation, multivariate regression analysis, P = 0.001), not hepatitis coinfection. CONCLUSIONS: Despite moderately enhanced lopinavir/ritonavir plasma concentrations, regular therapeutic drug monitoring is not to be considered in hepatitis-coinfected patients without hepatic impairment. Antiviral efficacy is comparable between both groups, a less-pronounced CD4(+) cell increase in hepatitis-coinfected patients is in line with previously published data.


Subject(s)
HIV Infections/drug therapy , Hepatitis B/drug therapy , Hepatitis C/drug therapy , Lopinavir/pharmacokinetics , Lopinavir/therapeutic use , Ritonavir/pharmacokinetics , Ritonavir/therapeutic use , Adult , Case-Control Studies , Chemistry, Pharmaceutical , Coinfection/drug therapy , Drug Combinations , HIV Infections/complications , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/pharmacokinetics , HIV Protease Inhibitors/therapeutic use , Hepatitis B/complications , Hepatitis C/complications , Humans , Liver/drug effects , Lopinavir/adverse effects , Male , Middle Aged , Ritonavir/adverse effects , Treatment Outcome , Viral Load
5.
BMC Res Notes ; 5: 527, 2012 Sep 25.
Article in English | MEDLINE | ID: mdl-23009598

ABSTRACT

BACKGROUND: Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. The sampling, handling and transport of specimens from patients with HIDs present specific bio-safety concerns. FINDINGS: The European Network for HID project aimed to record, in a cross-sectional study, the infection control capabilities of referral centers for HIDs across Europe and assesses the level of achievement to previously published guidelines. In this paper, we report the current diagnostic capabilities and bio-safety measures applied to diagnostic procedures in these referral centers. Overall, 48 isolation facilities in 16 European countries were evaluated. Although 81% of these referral centers are located near a biosafety level 3 laboratory, 11% and 31% of them still performed their microbiological and routine diagnostic analyses, respectively, without bio-safety measures. CONCLUSIONS: The discrepancies among the referral centers surveyed between the level of practices and the European Network of Infectious Diseases (EUNID) recommendations have multiple reasons of which the interest of the individuals in charge and the investment they put in preparedness to emerging outbreaks. Despite the fact that the less prepared centers can improve by just updating their practice and policies any support to help them to achieve an acceptable level of biosecurity is welcome.


Subject(s)
Communicable Diseases/diagnosis , Data Collection/statistics & numerical data , Hospitals, Isolation/standards , Infection Control/standards , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/standards , Cross-Sectional Studies , Data Collection/methods , Europe , Hospitals, Isolation/methods , Humans , Infection Control/methods , Microbiological Techniques/methods , Microbiological Techniques/standards
6.
Eur J Clin Pharmacol ; 66(4): 375-81, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20033681

ABSTRACT

OBJECTIVE: The human immundeficiency virus (HIV) protease inhibitor atazanavir is often used in once-daily observed therapy of methadone substituted former opiate drug users. We performed a matched-pairs analysis on 24 patients (12 men/women) taking atazanavir/ritonavir 300/100 mg daily plus reverse transcriptase inhibitors, with (n = 12) or without (n = 12) methadone co-administration. METHODS: Twenty-four-hour pharmacokinetic profiles of atazanavir/ritonavir were assessed at steady-state and measured by liquid chromatography-tandem mass spectrometry. The geometric mean (GM, t test) minimum and maximum plasma drug concentrations (C(min), C(max)), area under the concentration-time curve (AUC), and total clearance (CL(total)) were compared between the groups of pairs, which were matched for age, sex, weight, and ethnicity. RESULTS: The GM [90% confidence interval (CI)] of the atazanavir C(min), C(max), and AUC of patients taking the methadone oral solution at doses of 20-175 mg/day simultaneously with antiretroviral therapy were impaired compared to patients not taking methadone oral solution: C(min) = 315 (range 197-448) vs. 519 (279-793) ng/mL [GM ratio (GMR) = 0.61, p = 0.229]; C(max) = 1714 (1238-2262) vs. 3190 (2412-4076) ng/mL (GMR = 0.54, p = 0.018); AUC = 21,987 (15,870-29,327) vs. 35,572 (26,211-46,728) ng h/mL (GMR = 0.62, p = 0.074). Methadone dose, which is proportional to the amount of methadone oral solution (10 mg/mL), was significantly correlated to atazanavir C(max) (r (2) = 0.40, p = 0.001) and AUC (r (2) = 0.32, p = 0.006). Ritonavir pharmacokinetics was similar between the groups with C(min), C(max), and AUC GMR of 1.01, 0.80, and 0.96, respectively. CONCLUSION: The partial decrease in atazanavir plasma concentrations in patients concomitantly taking racemic methadone oral solution in this daily observed therapy setting deserves further attention, and therapeutic drug monitoring should be considered.


Subject(s)
HIV-1 , Methadone/therapeutic use , Oligopeptides/blood , Pyridines/blood , Reverse Transcriptase Inhibitors/blood , Virus Diseases/drug therapy , Adult , Atazanavir Sulfate , Chromatography, Liquid , Drug Monitoring , Female , Humans , Male , Oligopeptides/pharmacokinetics , Oligopeptides/therapeutic use , Pharmaceutical Solutions/therapeutic use , Plasma/virology , Pyridines/pharmacokinetics , Pyridines/therapeutic use , Reverse Transcriptase Inhibitors/pharmacokinetics , Reverse Transcriptase Inhibitors/therapeutic use , Ritonavir/administration & dosage , Ritonavir/adverse effects , Ritonavir/therapeutic use , Solutions/therapeutic use , Virus Diseases/virology
7.
J Med Virol ; 80(2): 192-200, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18098144

ABSTRACT

A human CD4-positive T cell line from a donor homozygous negative for the chemokine receptor CCR5 was established, characterized, and used for determining the coreceptor usage of human immunodeficiency virus type 1 (HIV-1) isolates. Clones of this IL-2 dependent human T-cell lymphotropic virus type 1 (HTLV-I) immortalized cell line, named IsnoR5 clones 1 and 2, are susceptible to infection by HIV-1 isolates that use CXCR4 as a coreceptor but resistant to infection by CCR5 tropic HIV-1 viruses. HIV-1 isolates whose replication is inhibited in IsnoR5 cells in the presence of the bicyclam AMD 3100, a CXCR4 specific inhibitor, utilize a coreceptor distinct from CCR5 and CXCR4. Using a panel of primary HIV-1 isolates we have shown that a single T cell line is sufficient to discriminate between use of CCR5, CXCR4 or an alternative coreceptor. As IsnoR5 clone 1 cells revealed the existence of even minor populations of CXCR4-using virus variants, they could be useful for the early identification of changes in coreceptor usage in HIV infected individuals facilitating the timely introduction of appropriate clinical treatments.


Subject(s)
CD4-Positive T-Lymphocytes/virology , HIV-1/classification , Receptors, CCR5/deficiency , Receptors, HIV/deficiency , Cell Line , Cell Transformation, Viral , HIV Infections/virology , HIV-1/growth & development , Human T-lymphotropic virus 1/physiology , Humans
8.
Drugs ; 64(7): 679-92, 2004.
Article in English | MEDLINE | ID: mdl-15025543

ABSTRACT

Before highly active antiretroviral therapies (HAART) were available for the treatment of persons with HIV infection, disseminated Mycobacterium avium-intracellulare complex (MAC) infection was one of the most common opportunistic infections that affected people living with AIDS. Routine use of chemoprophylaxis with a macrolide has been advocated in guidelines for the treatment of HIV-infected individuals if they have a circulating CD4+ cell count of < or =50 cells/microL. In addition, lifelong prophylaxis for disease recurrence has been recommended for those with a history of disseminated MAC infection. The introduction of HAART has resulted in a remarkable decline in the incidence of opportunistic infections and death among persons living with AIDS. Considerable reconstitution of functional immune responses against opportunistic infections can be achieved with HAART. In the case of infection with MAC, there has been a substantial reduction in the incidence of disseminated infections in the HAART era, even in countries where the use of MAC prophylaxis was never widely accepted. Moreover, the clinical picture of MAC infections in patients treated with potent antiretroviral therapies has shifted from a disseminated disease with bacteraemia to a localised infection, presenting most often with lymphadenopathy and osteomyelitis. Data from several recently conducted randomised, double-blind, placebo-controlled trials led to the current practice of discontinuing primary and secondary prophylaxis against disseminated MAC infections at stable CD4+ cell counts >100 cells/microL. These recommendations are still conservative as primary or secondary disseminated MAC infections are only rarely seen in patients who respond to HAART, despite treatment initiation at very low CD4+ cell counts. Potential adverse effects of macrolide therapy and drug interactions with antiretrovirals also metabolised via the cytochrome P450 enzyme system must be critically weighed against the marginal benefit that MAC prophylaxis may provide in addition to treatment with HAART. These authors feel that, unless patients who initiate HAART at low CD4+ cell counts do not respond to HIV-treatment, routine MAC prophylaxis should not be recommended. Nevertheless, the patient population for whom MAC prophylaxis may still be indicated in the era of HAART needs to be identified in prospectively designed clinical trials.


Subject(s)
Antibiotic Prophylaxis/methods , Antiretroviral Therapy, Highly Active/statistics & numerical data , Mycobacterium avium-intracellulare Infection/complications , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/prevention & control , Antibiotic Prophylaxis/trends , Antiretroviral Therapy, Highly Active/trends , Decision Making , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Mycobacterium avium-intracellulare Infection/drug therapy , Mycobacterium avium-intracellulare Infection/epidemiology , Randomized Controlled Trials as Topic
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