Posts filed under ‘Bacteriemias’

Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Antimicrob. Agents Chemother. May 2019 V.63 N.5

Matthew Geriak, Fadi Haddad, Khulood Rizvi, Warren Rose, Ravina Kullar, Kerry LaPlante, Marie Yu, Logan Vasina, Krista Ouellette, Marcus Zervos, Victor Nizet and George Sakoulas

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of >5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT02660346.)

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https://aac.asm.org/content/aac/63/5/e02483-18.full.pdf

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May 21, 2019 at 3:53 pm

Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents

Antimicrob. Agents Chemother. May 2019 V.63 N.5

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens” to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government.

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https://aac.asm.org/content/aac/63/5/e02309-18.full.pdf

May 21, 2019 at 3:52 pm

REVISION – Difusión de los antibióticos en el sistema nervioso central

Revista Española de Quimioterapia Febrero 2018 V.31 N.1 P.1–12.

José María Cabrera-Maqueda,corresponding author1 Luna Fuentes Rumí,1 Gabriel Valero López,1 Ana Esther Baidez Guerrero,1 Estefanía García Molina,1 José Díaz Pérez,1 and Elisa García-Vázquez2

RESUMEN

Las infecciones del SNC causadas por patógenos mutiresistentes suponen un reto terapéutico. El paso de fluidos y de solutos al SNC está estrechamente regulado a través de la BHE.La penetración de cualquier fármaco, inclusive los ATB, en el LCR depende del tamaño molecular, la lipofilicidad, la unión a proteínas plasmáticas y su afinidad por transportadores de la BHE. La relación entre el área bajo la curva en el LCR y el suero AUCCSF (Area Bajo la Curva en LCR)/AUCS (Area Bajo la Curva en suero) de una sustancia es el parámetro más preciso para determinar su capacidad de difusión.

Linezolid, algunas quinolonas y metronidazol consiguen altas concentraciones en LCR y son útiles para tratar microorganismos sensibles. Algunos ATB cuya permeabilidad a través de la BHE es baja pueden ser administrados directamente en el ventrículo a la vez que se realiza infusión IV. El ATB ideal para tratar una infección del SNC es pequeño, no tiene alta tasa de unión a proteínas plasmáticas, es moderadamente lipofílico y no es un ligando de alta afinidad a bombas de expulsión de la BHE.

Conocer la farmacocinética de los ATB y su interacción con la BHE permitirá mejorar el tratamiento de los pacientes con infecciones del SNC. En este artículo se exponen las propiedades físico-químicas de los principales grupos de ATB para evaluar cuáles son más prometedores en el tratamiento de las infecciones del SNC y cómo usarlos en la práctica clínica habitual.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159365/pdf/revespquimioter-31-1.pdf

May 19, 2019 at 7:13 pm

The widely used antimicrobial triclosan induces high levels of antibiotic tolerance in vitro and reduces antibiotic efficacy up to 100-fold in vivo.

Antimicrob Agents Chemother May 2019 V.63 N.5     

Westfall C et al.

The antimicrobial triclosan is used in a wide range of consumer products ranging from toothpaste, cleansers, socks, and baby toys. A bacteriostatic inhibitor of fatty acid synthesis, triclosan is extremely stable and accumulates in the environment.

Approximately 75% of adults in the United States have detectable levels of the compound in their urine, with a sizeable fraction of individuals (>10%) having urine concentrations equal to or greater than the minimal inhibitory concentration for Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA).

Previous work has identified connections between defects in fatty acid synthesis and accumulation of the alarmone guanosine tetraphosphate (ppGpp), which has been repeatedly associated with antibiotic tolerance and persistence.

Based on these data, we hypothesized that triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics.

Here we report that clinically relevant concentrations of triclosan increased E. coli and MRSA tolerance to bactericidal antibiotics as much as 10,000-fold in vitro and reduced antibiotic efficacy up to 100-fold in a mouse urinary tract infection model.

Genetic analysis indicated that triclosan-mediated antibiotic tolerance requires ppGpp synthesis but is independent of growth.

These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds.

FULL TEXT

https://aac.asm.org/content/63/5/e02312-18

PDF

https://aac.asm.org/content/aac/63/5/e02312-18.full.pdf

May 16, 2019 at 9:08 am

Clinical Infectious Diseases May 1, 2019 V.68 N.9 P.1456-1462

EDITOR’S CHOICE

Incidence of Acute Kidney Injury Among Critically Ill Patients With Brief Empiric Use of Antipseudomonal ß-Lactams With Vancomycin

Findings suggest that nephrotoxicity occurs after 3–5 days of piperacillin-tazobactam/vancomycin therapy. We found in a large observational study of intensive care unit patients that brief (<72-hour) empiric use of this combination was no more nephrotoxic than other such combinations.

Background

Nephrotoxins contribute to 20%–40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal ß-lactam/VAN combinations.

Methods

The study included a retrospective cohort of 3299 ICU patients who received =24 but =72 hours of an antipseudomonal ß-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups.

Results

The overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85–1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71–1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09).

Conclusion

Short courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.

FULL TEXT

https://academic.oup.com/cid/article/68/9/1456/5079140

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May 5, 2019 at 11:56 am

A Therapeutic Strategy for All Pneumonia Patients: A 3-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-resistant Pathogens to Select Initial Empiric Therapy

Clinical Infectious Diseases April 1, 2019 V.68 N.7 P.1080-1088 

EDITOR’S CHOICE

We applied a single algorithm to all forms of pneumonia, which was followed in 82.5% of a cohort of 1089 patients. Only 4.3% received inappropriate therapy; in multivariate analysis, site of pneumonia acquisition was not predictive of 30-day mortality.

Background

Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition.

Methods 

We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of  1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP).

Results

Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0–1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0–1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit <30%, malnutrition, dehydration, and chronic liver disease), as well as hypotension and inappropriate therapy were significantly correlated with 30-day mortality, whereas the classification of pneumonia type (VAP, HAP, HCAP, CAP) was not.

Conclusions

Individual MDR risk factors can be used in a unified algorithm to guide and simplify empiric therapy for all pneumonia patients, and were more important than the classification of site of pneumonia acquisition in determining 30-day mortality.

FULL TEXT

https://academic.oup.com/cid/article/68/7/1080/5063558

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May 4, 2019 at 12:14 pm

Performance of Treponemal Tests for the Diagnosis of Syphilis

Clinical Infectious Diseases March 15, 2019 V.68 N.6 P.913–918

Performance of Treponemal Tests for the Diagnosis of Syphilis

We compared performance of 5 treponemal immunoassays, the Treponema pallidum particle agglutination assay (TPPA), and the fluorescent treponemal antibody absorption test (FTA-ABS). FTA-ABS was less sensitive for primary syphilis (78%) than the immunoassays or TPPA (94%–96% sensitivity). TPPA was 100% specific.

Background

Treponemal immunoassays are increasingly used for syphilis screening with the reverse sequence algorithm. There are few data describing performance of treponemal immunoassays compared to traditional treponemal tests in patients with and without syphilis.

Methods

We calculated sensitivity and specificity of 7 treponemal assays: (1) ADVIA Centaur (chemiluminescence immunoassay [CIA]); (2) Bioplex 2200 (microbead immunoassay); (3) fluorescent treponemal antibody absorption test (FTA-ABS); (4) INNO-LIA (line immunoassay); (5) LIAISON CIA; (6) Treponema pallidum particle agglutination assay (TPPA); and (7) Trep-Sure (enzyme immunoassay [EIA]), using a reference standard combining clinical diagnosis and serology results. Sera were collected between May 2012–January 2013. Cases were characterized as: (1) current clinical diagnosis of syphilis: primary, secondary, early latent, late latent; (2) prior treated syphilis only; (3) no evidence of current syphilis, no prior history of syphilis, and at least 4 of 7 treponemal tests negative.

Results

Among 959 participants, 262 had current syphilis, 294 had prior syphilis, and 403 did not have syphilis. FTA-ABS was less sensitive for primary syphilis (78.2%) than the immunoassays or TPPA (94.5%–96.4%) (all P ≤ .01). All immunoassays were 100% sensitive for secondary syphilis, 95.2%–100% sensitive for early latent disease, and 86.8%–98.5% sensitive in late latent disease. TPPA had 100% specificity.

Conclusions

Treponemal immunoassays demonstrated excellent sensitivity for secondary, early latent, and seropositive primary syphilis. Sensitivity of FTA-ABS in primary syphilis was poor. Given its high specificity and superior sensitivity, TPPA is preferred to adjudicate discordant results with the reverse sequence algorithm over the FTA-ABS.

FULL TEXT

https://academic.oup.com/cid/article/68/6/913/5050740

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Clinical Infectious Diseases March 15, 2019 V.68 N.6 P.934–939

Syphilis Testing Among Sexually Active Men Who Have Sex With Men and Who Are Receiving Medical Care for Human Immunodeficiency Virus in the United States: Medical Monitoring Project, 2013–2014

Among sexually active HIV-positive men who have sex with men in the United States receiving medical care for HIV, nearly one-third were not tested for syphilis at least annually and many at increased risk were not tested at recommended frequencies.

Background

Guidelines recommend that sexually active men who have sex with men (MSM) including human immunodeficiency virus (HIV)-positive MSM be tested at least annually for syphilis, with testing every 3–6 months for MSM at elevated risk. We examined the proportion of HIV-positive MSM tested for syphilis in the past 3, 6, and 12 months by their HIV care provider during 2013–2014.

Methods

Using data from the Medical Monitoring Project, a population-based HIV surveillance system, we evaluated the proportion of MSM who had documentation of being tested for syphilis by their HIV care provider in the past 3, 6, and 12 months.

Results

During 2013–2014, 71% (95% confidence interval [CI]: 69%–73%) of sexually active HIV-positive MSM were tested for syphilis in the past year. This proportion was higher among MSM reporting condomless sex: (75%; 95% CI: 72%–78%), and among MSM reporting ≥ 2 sex partners (77%; 95% CI: 74%–79%), in the past 12 months. Among MSM reporting condomless sex, 49% (95% CI: 45%–53%) were tested in the past 6 months, and 26% (95% CI: 22%–30%) in the past 3 months. Among MSM reporting ≥ 2 sex partners, 49% (95% CI: 44%–54%) were tested in the past 6 months and 26% (95% CI: 22%–29%) in the past 3 months.

Conclusions

Nearly one-third of sexually active HIV-positive MSM were not tested annually, and many at increased risk were not tested at recommended frequencies. Efforts to improve compliance with screening guidelines for high-risk HIV-positive MSM are warranted.

FULL TEXT

https://academic.oup.com/cid/article/68/6/934/5050272

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May 4, 2019 at 12:08 pm

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