Archive for September 12, 2014

Blunted response to combination antiretroviral therapy in HIV elite controllers: an international HIV controller collaboration.

PLoS One. 2014 Jan 17;9(1):e85516.

Boufassa F1, Lechenadec J2, Meyer L3, Costagliola D4, Hunt PW5, Pereyra F6, Deeks S5, Pancino G7, Taulera O8, Lichterfeld M9, Delobel P10, Saez-Cirion A7, Lambotte O11; ANRS CO18 HIV Controllers Cohort; Cascade Collaboration in Eurocoord; SCOPE Cohort; International HIV Controllers Study.

Author information

1Inserm, CESP Centre for research in Epidemiology and Population Health, Epidemiology of HIV and STI Team, le Kremlin-Bicêtre, France ; Univ Paris-Sud, Le Kremlin Bicêtre, France.

2Univ Paris-Sud, Le Kremlin Bicêtre, France.

3Inserm, CESP Centre for research in Epidemiology and Population Health, Epidemiology of HIV and STI Team, le Kremlin-Bicêtre, France ; Univ Paris-Sud, Le Kremlin Bicêtre, France ; AP-HP, Service de Santé Publique, Hôpital de Bicêtre, le Kremlin Bicêtre, France.

4UPMC Univ Paris 06, Paris, France ; INSERM, Paris, France.

5Laboratory Medicine, Departments of Medicine, Epidemiology, and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.

6The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts, United States of America.

7Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.

8Hôpital Saint-Louis, Paris, France.

9Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

10Service des Maladies Infectieuses et Tropicales, Hôpital Purpan, Toulouse, France ; INSERM, Toulouse, France.

11AP-HP, Service de Médecine Interne, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.

Abstract

OBJECTIVE:

HIV “elite controllers” (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs).

METHODS:

ECs were defined as patients with at least ≥5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (<1 year) ART-naïve HIV-1-infected adults. CD4 T-cell count dynamics after cART initiation in both groups were modelled with piecewise mixed linear models.

RESULTS:

After cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63√CD4/month), followed by +0.19√CD4/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm(3), the estimated mean CD4 T-cell gain during the first 12 months was 139/mm(3) in VIRs and 80/mm(3) in ECs (p = 0.048).

CONCLUSIONS:

cART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894966/pdf/pone.0085516.pdf

September 12, 2014 at 8:43 am

Continuous infusion of antibiotics in the critically ill: The new holy grail for beta-lactams and vancomycin?

Annals of Intensive Care 2012 V.2 P.22

REVIEW

Bruno Van Herendael1*, Axel Jeurissen2, Paul M Tulkens3, Erika Vlieghe4,5, Walter Verbrugghe6,

Philippe G Jorens6 and Margareta Ieven

The alarming global rise of antimicrobial resistance combined with the lack of new antimicrobial agents has led to a renewed interest in optimization of our current antibiotics.

Continuous infusion (CI) of time-dependent antibiotics has certain theoretical advantages toward efficacy based on pharmacokinetic/pharmacodynamic principles.

We reviewed the available clinical studies concerning continuous infusion of beta-lactam antibiotics and vancomycin in critically ill patients.

We conclude that CI of beta-lactam antibiotics is not necessarily more advantageous for all patients.

Continuous infusion is only likely to have clinical benefits in subpopulations of patients where intermittent infusion is unable to achieve an adequate time above the minimal inhibitory

concentration (T > MIC). For example, in patients with infections caused by organisms with elevated MICs, patients with altered pharmacokinetics (such as the critically ill) and possibly also immunocompromised patients. For vancomycin CI can be chosen, not always for better clinical efficacy, but because it is practical, cheaper, associated with less AUC24h (area under the curve >24 h)-variability, and easier to monitor.

PDF

http://www.annalsofintensivecare.com/content/pdf/2110-5820-2-22.pdf

September 12, 2014 at 8:39 am

Continuous versus Intermittent Infusion of Vancomycin in Severe Staphylococcal Infections: Prospective Multicenter Randomized Study

Antimicrobial Agents and Chemotherapy Sept 2001 V.45 N.9 P.2460-2467

Marc Wysocki1,*, Frederique Delatour2, François Faurisson2, Alain Rauss, Yves Pean4, Benoit Misset5, Frank Thomas6, Jean-François Timsit7, Thomas Similowski8, Herve Mentec9, Laurence Mier10, Didier Dreyfuss10, and The Study Group†

Medico-Surgical Intensive Care Unit1and

Microbiology,4 Institut Mutualiste Montsouris,

Medico-Surgical Intensive Care Unit, Hôpital Saint-Joseph,5

Medico-Surgical Intensive Care Unit, Hôpital de Diaconesses,6

INSERM U132 and

Infectious Diseases Critical Care Unit,7 Hôpital Bichat-Claude Bernard, and

Respiratory Intensive Care Unit, Hôpital de la Pitié-Salpêtrière,8Paris,

Medico-Surgical Intensive Care Unit, Hôpital V. Dupouy, Argenteuil,9 and

Medical Intensive Care Unit, Hôpital Louis Mourier, Colombes,10 France

A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections.

A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%).

Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar.

CIV patients reached the targeted concentrations faster (36 ± 31 versus 51 ± 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 ± 2.2 versus 11.8 ± 3.9 per treatment, P < 0.0001).

The variability between patients in both the area under the serum concentration-time curve (AUC24h) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg2/liter2/h2[P = 0.026] and 414 versus 818 g2[P = 0.057], respectively).

The 10-day treatment cost per patient was $454 ± 137 in the IIV group and was 23% lower in the CIV group ($321 ± 81: P < 0.0001).

In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.

PDF

http://aac.asm.org/content/45/9/2460.full.pdf+html

September 12, 2014 at 8:38 am

Resistance to “last resort” antibiotics in Gram-positive cocci: The post-vancomycin era.

Biomedica. 2014 Apr;34 Suppl 1:191-208.

Article in Spanish

Rincón S1, Panesso D1, Díaz L1, Carvajal LP1, Reyes J2, Munita JM3, Arias CA1.

Author information

1Unidad de Genética y Resistencia Antimicrobiana (UGRA), Universidad El Bosque, Bogotá, D.C, Colombia.

2University of Texas Medical School at Houston, Houston, TX, USA.

3Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago de Chile, Chile.

Abstract

New therapeutic alternatives have been developed in the last years for the treatment of multidrug-resistant Gram-positive infections.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are considered a therapeutic challenge due to failures and lack of reliable antimicrobial options.

Despite concerns related to the use of vancomycin in the treatment of severe MRSA infections in specific clinical scenarios, there is a paucity of solid clinical evidence that support the use of alternative agents (when compared to vancomycin).

Linezolid, daptomycin and tigecycline are antibiotics approved in the last decade and newer cephalosporins (such as ceftaroline and ceftobiprole) and novel glycopeptides (dalvavancin, telavancin and oritavancin) have reached clinical approval or are in the late stages of clinical development.

This review focuses on discussing these newer antibiotics used in the “post-vancomycin” era with emphasis on relevant chemical characteristics, spectrum of antimicrobial activity, mechanisms of action and resistance, as well as their clinical utility.

PDF

http://www.scielo.org.co/pdf/bio/v34s1/v34s1a22.pdf

September 12, 2014 at 8:35 am

Unmet needs and prospects for oritavancin in the management of vancomycin-resistant enterococcal infections.

Clin Infect Dis. 2012 Apr;54 Suppl 3:S233-8.

Arias CA1, Mendes RE, Stilwell MG, Jones RN, Murray BE.

Author information

1Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical School, 6431 Fannin St, Houston, TX 77030, USA.

Abstract

The treatment of infections caused by vancomycin-resistant enterococci (VRE) has become an important clinical challenge and compromises the care of critically ill patients.

A striking increase in the frequency of nosocomial isolation of multidrug-resistant Enterococcus faecium has dramatically reduced the therapeutic alternatives because the majority of E. faecium isolates are resistant to ampicillin and vancomycin.

Only 2 agents have US Food and Drug Administration approval for the treatment of VRE (E. faecium) infections, namely, linezolid and quinupristin/dalfopristin (Q/D).

However, the use of these compounds in severe VRE infections is hampered by the lack of in vivo bactericidal activity, reports of therapeutic failures with monotherapy, a requirement for central venous access for administration (Q/D), and adverse-effect profile.

The lipopeptide antimicrobial daptomycin has in vitro bactericidal activity against VRE; however, clinical use of this compound for VRE has not been well studied, and the reports of resistance emerging during therapy at the approved doses are worrisome. Tigecycline has in vitro bacteriostatic activity against VRE, but its clinical use for serious enterococcal infections is unclear due to low serum levels and static effect.

Thus, current reliable therapies for VRE appear to be limited, and clinical data that use the above compounds are certainly scant. Oritavancin is an investigational semisynthetic glycopeptide with potent in vitro activity against VRE (both VanA and VanB phenotypes).

Although review of the available preclinical data indicates that this compound used as a single agent is likely to have important limitations for the treatment of a severe VRE infection (ie, endocarditis), combination of oritavancin with other agents such as aminoglycosides may offer promise and deserves further investigation, as does use of oritavancin for less serious infections as monotherapy for vancomycin-susceptible and multidrug-resistant enterococci.

PDF

http://cid.oxfordjournals.org/content/54/suppl_3/S233.full.pdf+html

September 12, 2014 at 8:33 am


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