Posts filed under ‘HIC no SIDA’

Pharmacokinetics of anidulafungin in critically ill patients with candidemia/invasive candidiasis.

Antimicrob Agents Chemother. 2013 Apr;57(4):1672-6.

Liu P1, Ruhnke M, Meersseman W, Paiva JA, Kantecki M, Damle B.

Author information

1 Clinical Pharmacology, Specialty Care, Pfizer Inc, Groton, Connecticut, USA.

Abstract

The pharmacokinetics of intravenous anidulafungin in adult intensive care unit (ICU) patients were assessed in this study and compared with historical data from a general patient population and healthy subjects. Intensive plasma sampling was performed over a dosing interval at steady state from 21 ICU patients with candidemia/invasive candidiasis. All patients received the recommended dosing regimen (a 200-mg loading dose on day 1, followed by a daily 100-mg maintenance dose), except for a 54-year-old 240-kg female patient (who received a daily 150-mg maintenance dose instead). Plasma samples were assayed for anidulafungin using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters in ICU patients were calculated by a noncompartmental method. With the exclusion of the 240-kg patient, the median (minimum, maximum) age, weight, and body mass index (BMI) of 20 ICU patients were 57 (39, 78) years, 65 (48, 106) kg, and 23.3 (16.2, 33.8) kg/m(2), respectively. The average anidulafungin area under the curve over the 24-hour dosing interval (AUC(0-24)), maximum concentration (C(max)), and clearance (CL) in 20 ICU patients were 92.7 mg · h/liter, 7.7 mg/liter, and 1.3 liters/h, respectively. The exposure in the 240-kg patient at a daily 150-mg dose was within the range observed in ICU patients overall. The average AUC(0-24) and Cmax in the general patient population and healthy subjects were 110.3 and 105.9 mg · h/liter and 7.2 and 7.0 mg/liter, respectively. The pharmacokinetics of anidulafungin in ICU patients appeared to be comparable to those in the general patient population and healthy subjects at the same dosing regimen.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623353/pdf/zac1672.pdf

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July 7, 2018 at 3:36 pm

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.

Clinical Infectious Diseases  March 1, 2009 V.48 N.5 P. 503-35.

Pappas PG1, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD; Infectious Diseases Society of America.

Author information

1 Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama 35294-0006, USA. pappas@uab.edu

Abstract

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

abstract

https://academic.oup.com/cid/article/48/5/503/382619

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July 7, 2018 at 3:34 pm

Anidulafungin versus fluconazole for invasive candidiasis.

N Engl J Med. June 14, 2007 V.356 N.24 P.2472-82.

Reboli AC1, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, Betts R, Wible M, Goldstein BP, Schranz J, Krause DS, Walsh TJ; Anidulafungin Study Group.

Author information

1 University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Cooper University Hospital, Camden, NJ 08103, USA. reboli-annette@cooperhealth.edu

Abstract

BACKGROUND:

Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority trial of treatment for invasive candidiasis.

METHODS:

Adults with invasive candidiasis were randomly assigned to receive either intravenous anidulafungin or intravenous fluconazole. All patients could receive oral fluconazole after 10 days of intravenous therapy. The primary efficacy analysis assessed the global response (clinical and microbiologic) at the end of intravenous therapy in patients who had a positive baseline culture. Efficacy was also assessed at other time points.

RESULTS:

Eighty-nine percent of the 245 patients in the primary analysis had candidemia only. Candida albicans was isolated in 62% of the 245 patients. In vitro fluconazole resistance was infrequent. Most of the patients (97%) did not have neutropenia. At the end of intravenous therapy, treatment was successful in 75.6% of patients treated with anidulafungin, as compared with 60.2% of those treated with fluconazole (difference, 15.4 percentage points; 95% confidence interval [CI], 3.9 to 27.0). The results were similar for other efficacy end points. The statistical analyses failed to show a “center effect”; when data from the site enrolling the largest number of patients were removed, success rates at the end of intravenous therapy were 73.2% in the anidulafungin group and 61.1% in the fluconazole group (difference, 12.1 percentage points; 95% CI, -1.1 to 25.3). The frequency and types of adverse events were similar in the two groups. The rate of death from all causes was 31% in the fluconazole group and 23% in the anidulafungin group (P=0.13).

CONCLUSIONS:

Anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. (ClinicalTrials.gov number, NCT00056368 [ClinicalTrials.gov]).

FULL TEXT

https://www.nejm.org/doi/10.1056/NEJMoa066906?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

PDF

https://www.nejm.org/doi/pdf/10.1056/NEJMoa066906

July 7, 2018 at 3:31 pm

Clinical and Epidemiological Features of Enterococcus casseliflavus/flavescens and Enterococcus gallinarum Bacteremia: A Report of 20 Cases

Clinical Infectious Diseases June 1, 2001 V.32 N.11 P.1540-1546

Karlene C. Reid  Franklin R. Cockerill, III  Robin Patel

The clinical significance of intrinsically vancomycin-resistant enterococci is not yet fully established, as these organisms are infrequently recovered from clinical specimens. We report our experience with 20 cases of Enterococcus gallinarum and Enterococcus casseliflavus/flavescens bacteremia in humans from 1992 through 1998. Sixteen cases of bacteremia were caused by E. gallinarum. Underlying conditions were present in 19 (95%) of the patients and included malignancy, receipt of transplant, and Caroli’s disease. Polymicrobial bacteremia was present in 9 patients (45%). E. gallinarum and E. casseliflavus/flavescens, although they are infrequently isolated from clinical specimens, may cause serious invasive infections.

La importancia clínica de los enterococos intrínsecamente resistentes a la vancomicina todavía no está completamente establecida, ya que estos organismos se recuperan con poca frecuencia de las muestras clínicas. Presentamos nuestra experiencia con 20 casos de bacteriemias en humanos por Enterococcus gallinarum y Enterococcus casseliflavus/flavescens bacteriemia 1992 hasta 1998.

Dieciséis casos de bacteriemia fueron causados por E. gallinarum. Las condiciones subyacentes estuvieron presentes en 19 (95%) de los pacientes e incluyeron malignidad, recepción de trasplante y enfermedad de Caroli.

La bacteriemia polimicrobiana estuvo presente en 9 pacientes (45%). E. gallinarum y E. casseliflavus / flavescens, aunque rara vez se aíslan de muestras clínicas, pueden causar infecciones invasivas graves.

FULL TEXT

https://academic.oup.com/cid/article/32/11/1540/461246

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June 8, 2018 at 8:23 am

Relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines among Veterans Health Administration patients.

Journal of Infectious Diseases May 5,  2018  V.217 N.11 P.1718-1727  

Young-Xu Y et al.

We examined whether a high-dose inactivated influenza vaccine was more efficacious in preventing hospitalizations than a standard-dose vaccine in the Veterans Health Administration (VHA) senior population.

Methods

This study estimated the relative vaccine effectiveness (rVE) of high dose versus standard dose using a retrospective cohort of VHA patients 65 years of age or older in the 2015–2016 influenza season. To adjust for measured confounders, we matched each high-dose recipient with up to 4 standard-dose recipients vaccinated at the same location within a 2-week period and having 2 or more pre-existing medical comorbidities. We used the previous event rate ratio method (PERR), a type of difference-in-differences analysis, to adjust for unmeasured confounders.

Results

We evaluated 104965 standard-dose and 125776 high-dose recipients; matching decreased the population to 49091 standard-dose and 24682 high-dose recipients. The matched, PERR-adjusted rVE was 25% (95% confidence interval [CI], 2%–43%) against influenza- or pneumonia-associated hospitalization, 7% (95% CI, −2% to 14%) against all-cause hospitalization, 14% (95% CI, −8% to 32%) against influenza- or pneumonia-associated outpatient visit, 5% (95% CI, 2%–8%) against all-cause outpatient visit, and 38% (95% CI, −5% to 65%) against laboratory-confirmed influenza.

Conclusions

In protecting senior VHA patients against influenza- or pneumonia-associated hospitalization, a high-dose influenza vaccine is more effective than a standard-dose vaccine.

FULL TEXT

https://academic.oup.com/jid/article/217/11/1718/4858294

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May 31, 2018 at 8:30 am

Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids

Ann Rheum Dis. May 2018 V.77 N.5 P.644-649.

Park JW1, Curtis JR2, Moon J1, Song YW1, Kim S3,4, Lee EB1.

Author information

1 Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

2 Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

3 Division of Nephrology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

4 Seoul Kidney Clinic, Seoul, Republic of Korea.

Abstract

OBJECTIVES:

To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.

METHODS:

The study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).

RESULTS:

During a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8-29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33-124)) was lower than the number needed to harm for serious ADR (131 (55-∞)).

CONCLUSION:

TMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909751/pdf/annrheumdis-2017-211796.pdf

May 10, 2018 at 8:42 am

Infectious Diseases Consultation Reduces 30-Day and 1-Year All-Cause Mortality for Multidrug-Resistant Organism Infections.

Open Forum Infect Dis. Match 15, 2018 V.5 N.3

Burnham JP1, Olsen MA1, Stwalley D1, Kwon JH1, Babcock HM1, Kollef MH2.

Author information

1 Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri.

2 Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri.

Abstract

BACKGROUND:

Multidrug-resistant organism (MDRO) infections are associated with high mortality and readmission rates. Infectious diseases (ID) consultation improves clinical outcomes for drug-resistant Staphylococcus aureus bloodstream infections. Our goal was to determine the association between ID consultation and mortality following various MDRO infections.

METHODS:

This study was conducted with a retrospective cohort (January 1, 2006-October 1, 2015) at an academic tertiary referral center. We identified patients with MDROs in a sterile site or bronchoalveolar lavage/bronchial wash culture. Mortality and readmissions within 1 year of index culture were identified, and the association of ID consultation with these outcomes was determined using Cox proportional hazards models with inverse weighting by the propensity score for ID consultation.

RESULTS:

A total of 4214 patients with MDRO infections were identified. ID consultation was significantly associated with reductions in 30-day and 1-year mortality for resistant S. aureus (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36-0.63; and HR, 0.73, 95% CI, 0.61-0.86) and Enterobacteriaceae (HR, 0.41; 95% CI, 0.27-0.64; and HR, 0.74; 95% CI, 0.59-0.94), and 30-day mortality for polymicrobial infections (HR, 0.51; 95% CI, 0.31-0.86) but not Acinetobacter or Pseudomonas. For resistant Enterococcus, ID consultation was marginally associated with decreased 30-day mortality (HR, 0.81; 95% CI, 0.62-1.06). ID consultation was associated with reduced 30-day readmission for resistant Enterobacteriaceae.

CONCLUSIONS:

ID consultation was associated with significant reductions in 30-day and 1-year mortality for resistant S. aureus and Enterobacteriaceae, and 30-day mortality for polymicrobial infections. There was no association between ID consultation and mortality for patients with resistant Pseudomonas, Acinetobacter, or Enterococcus, possibly due to small sample sizes. Our results suggest that ID consultation may be beneficial for patients with some MDRO infections.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852998/pdf/ofy026.pdf

May 10, 2018 at 8:41 am

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