Association of Virus Load, CD4 Cell Count, and Treatment with Clinical Progression in Human Immunodeficiency Virus-Infected Patients with Very Low CD4 Cell Counts

This study prospectively assessed the impact of treatment modality, virus load, and CD4 cell count of <50 cells/mm3 on human immunodeficiency virus disease progression. The incidence rate of new AIDS disease or death was 54.8 (95% confidence interval, 48.7-59.9) per 100 person-years of follow-up. Independent predictors related to progression were latest CD4 cell count (relative risk [RR], 0.84/10 mm3 higher; P<.0001), latest hemoglobin level (RR, 0.79/g/L higher; P<.0001), Pneumocystis carinii pneumonia prophylaxis (RR, 0.49; P<.0001), latest body mass index (RR, 0.93/kg/m2 higher; P=.002), latest virus load (RR, 1.11/log10 higher; P=.03), and intensity of treatment (RR, 1.82, P=.004; RR 2.27, P<.0001; RR 2.46, P=.0001; RR 2.33 P<.0006; 5.10, P<.0001, respectively, for 4, 3, 2, 1, or no drugs vs. ⩾5 drugs). Although reverse causality cannot be excluded, more intense antiviral treatment appears to decrease the risk of progression in immunocompromised patient

Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: An open-label Phase IIIb/IV study (PROFILE)

©The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. Objectives Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD. Methods The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591. Results Median T max of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1-2 h across Days 1, 5 and 10. C max ranges were 1.2-154 ng/mL for fidaxomicin and 4.7-555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8-2170 μg/g for fidaxomicin and 0-1940 μg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death. Conclusions Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD

Prescription of antibiotics and knowledge about antibiotic costs among physicians working in tertiary-care hospitals

The objective of this study is to investigate antibiotic prescription practices among hospital-based physicians in Greece, using the 2007 national guidelines as the golden standard. A total of 168 physicians participated. Compliance rate with the first-line antibiotic treatment recommended by the national guidelines was 65.5% for acute bacterial sinusitis; 24% for acute uncomplicated cystitis; 36.4% for an acute febrile diarrheic syndrome; 38% for an afebrile adult with chronic obstructive pulmonary disease and nonproductive cough of 7 days duration; 23.2% for streptococcal pharyngotonsillitis; 55.1% for a surgically sutured, dirty wound; and 48.2% for community-acquired pneumonia. The total mean rate of compliance with the first recommended antibiotic was 41.2%

Chronic renal failure among HIV-1-infected patients

BACKGROUND: The role of exposure to antiretrovirals in chronic renal failure (CRF) is not well understood. Glomerular filtration rates (GFR) are estimated using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations. METHODS: Baseline was arbitrarily defined as the first recorded GFR; patients with two consecutive GFR < or = 60 ml/min per 1.73 m(2) were defined as having CRF. Logistic regression was used to determine odds ratio (OR) of CRF at baseline. ART exposure (yes/no or cumulative exposure) prior to baseline was included in multivariate models (adjusted for region of Europe, age, prior AIDS, CD4 cell count nadir, viral load, hypertension and use of nephrotoxic anti-infective therapy). RESULTS: Using CG, the median GFR at baseline (n = 4474) was 94.4 (interquartile range, 80.5-109.3); 158 patients (3.5%) had CRF. Patients with CRF were older (median, 61.9 versus 43.1 years), had lower CD4 cell count nadirs (median, 80 versus 137 cells/microl), and were more likely to be diagnosed with AIDS (44.3 versus 30.4%), diabetes (16.5 versus 4.3%) or hypertension (53.8 versus 26.4%), all P < 0.001. In a multivariate model any use of indinavir [odds ratio (OR) 2.49; 95% confidence interval (CI), 1.62-3.83] or tenofovir (OR, 2.18; 95% CI, 1.25-3.81) was associated with increased odds of CRF, as was cumulative exposure to indinavir (OR, 1.15 per year of exposure; 95% CI, 1.06-1.25) or tenofovir (OR, 1.60; 95% CI, 1.20-2.15). Highly consistent results were seen using the MDRD formula. CONCLUSIONS: Among antiretrovirals, only exposure to indinavir or tenofovir was associated with increased odds of CRF. We used a confirmed low GFR to define CRF to increase the robustness of our analysis, although there are several potential biases associated with this cross-sectional analysi

Association of Virus Load, CD4 Cell Count, and Treatment with Clinical Progression in Human Immunodeficiency Virus–Infected Patients with Very Low CD4 Cell Counts

This study prospectively assessed the impact of treatment modality, virus load, and CD4 cell count of <50 cells/mm3 on human immunodeficiency virus disease progression. The incidence rate of new AIDS disease or death was 54.8 (95% confidence interval, 48.7-59.9) per 100 person-years of follow-up. Independent predictors related to progression were latest CD4 cell count (relative risk [RR], 0.84/10 mm3 higher; P<.0001), latest hemoglobin level (RR, 0.79/g/L higher; P<.0001), Pneumocystis carinii pneumonia prophylaxis (RR, 0.49; P<.0001), latest body mass index (RR, 0.93/kg/m2 higher; P=.002), latest virus load (RR, 1.11/log10 higher; P=.03), and intensity of treatment (RR, 1.82, P=.004; RR 2.27, P<.0001; RR 2.46, P=.0001; RR 2.33 P<.0006; 5.10, P<.0001, respectively, for 4, 3, 2, 1, or no drugs vs. ⩾5 drugs). Although reverse causality cannot be excluded, more intense antiviral treatment appears to decrease the risk of progression in immunocompromised patient

The Role of Macrolides for the Management of Community-Acquired Pneumonia and Pneumonia by the Novel Coronavirus SARS-CoV-2 (COVID-19): A Position Paper by Four Medical Societies from Greece

In light of the accumulating evidence for survival benefit coming from the use of macrolides for community-acquired pneumonia (CAP), a group of experts from the field of internal medicine and infectious diseases frame a position statement on the use of macrolides for the management of bacterial CAP and for infection by the novel coronavirus (COVID-19). The statement is framed taking into consideration existing publications and own research experience. The main content of this statement is that the combination of one beta-lactam and a macrolide should be the first treatment of choice for patients with severe bacterial CAP. Severity is assessed as scoring 2 or more points on the CURB65 scoring system of severity or as pneumonia severity index III to V or C-reactive protein more than 150 mg/l; the suggested macrolide is either azithromycin or clarithromycin. The experts also suggest that in COVID-19 pneumonia, the combination of one beta-lactam and a macrolide should be reserved only when there is strong suspicion of bacterial co-infection