Archive for September 1, 2011

Development of Antiretroviral Drug Resistance

N Engl J of Med  Aug.18, 2011 V.365 P.637-646

Review Article

Mechanisms of Disease

Mark A. Wainberg, Ph.D., Gerasimos J. Zaharatos, M.D., and Bluma G. Brenner, Ph.D.

Combinations of antiretroviral drugs are efficacious in the treatment of human immunodeficiency virus (HIV) infection, regardless of the viral subtype. However, the level of resistance to antiretroviral drugs differs among HIV variants. Indeed, we have limited knowledge of resistance mutations in non-B subtypes of HIV type 1 (HIV-1) and their clinical relevance, despite the fact that more than 90% of patients with HIV-1 infection worldwide have non–subtype B variants of HIV-1. Most reports on drug resistance deal with subtype B infections in developed countries. Both enzymatic and virologic data indicate that naturally occurring polymorphisms among different HIV subtypes can influence HIV-1 susceptibility to individual antiretroviral drugs and the propensity of HIV to acquire certain resistance mutations. Furthermore, resistance pathways in different subtypes may affect drug cross-resistance and the potential use of specific second-line regimens. This concern may be increased in developing countries….



September 1, 2011 at 11:39 pm Leave a comment

Colistín en infecciones nosocomiales por bacilos gramnegativos pan-resistentes

Rev Chil Infect 2007 V.24 N.5 P.360-367

Alberto Fica C., Ignacio Céspedes J., Macarena Gompertz G., Mauricio Jalón V., Andrea Sakurada Z. y Enzo Sáez L.

Hospital Clínico Universidad de Chile, Santiago, Chile Sección de Infectología (AFC) Departamento de Medicina (ICJ, MGG, MJV) Laboratorio Central (ASZ) Unidad de Pacientes Críticos (ESL)

Emergence of panresistant gram negative bacilli has lead to the progressive reintroduction of intravenous colistin. Aim: To describe the clinical experience observed with this compound. Methodology: A retrospective analysis was performed for all treatments lasting > 48 hours. Medical records were analyzed to obtain clinical

parameters and microbiological data, evaluate clinical response and evolution until discharge. Main results: 24 treatments lasting > 48 hours were applied between June 2005 and September 2006. Intravenous colistin was indicated to treat cases of ventilator-associated (VA) pneumonia (n = 10; 41.7%), abscess or collections (12.5%), bloodstream infections, non-VA pneumonia or urinary tract infections (4.2% each one, respectively). Treatment was initiated on average at 3.2 days (± 2.85) from diagnosis of infection. All courses were microbiologically-guided, and involved P. aeruginosa or A. baumannii isolates. Susceptibility was evaluated by E-test in 11 isolates (MIC90 3.6 μg/mL, range 0.38 to 4 μg/mL). One isolate was resistant to colistin (9%). A favorable response was observed in 12 treatments (50%) with a relapse in 5 cases (41.7%). Being treated for pneumonia was the only factor associated to failure. (p = 0.04) Eradication  was documented in 8 cases (33.3%) and persistence in 11 (45.8%). In 5 cases a microbiological follow-up was not available. Survival at time of discharge was 45.5%. (n = 10) None of the treatment courses was associated with nefrotoxicity. Conclusions:

Intravenous colistin is a safe compound useful to treat various nosocomial infections due to pan-resistant gram negative bacilli. Nonetheless, its clinical efficacy is limited, especially among patients treated for nosocomial pneumonia.

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September 1, 2011 at 11:37 pm Leave a comment

Aerosolized colistin in the treatment of multiresistant Pseudomonas aeruginosa nosocomial pneumonia

Signa Vitae 2009 V.4 N.2 P.30-31

Boubaker Charra, Abdelhamid Hachimi, Abdellatif Benslama, Said Motaouakkil



Multiresistant Pseudomonas aeruginosa (MRPA) nosocomial pneumonia is a significant cause of mortality and morbidity in the ICU. We report our experience with aerosolized colistin in the treatment of MRPA nosocomial pneumonia.

Patients and methods

It is a prospective, observational study performed over 2 years (2006-2007). Patients who developed MRPA nosocomial pneumonia and were treated with aerosolized colistin were included. The criteria used to assess if treatment was successful were extubation and ICU mortality rates.


We report 32 patients of whom 12 were women and 20 men. The mean age was 48 ± 19 years. All patients were receiving mechanical ventilation. The mean length of ventilation was 22 ± 5.5 days. The bronchial sampling technique used was broncho-alveolar lavage. The mean delay of infection (duration between intubation and pneumonia diagnosis) was 7 ± 2 days. Isolated MRPA was susceptible only to colistin. The treatment was aerosolized colistin for all patients (4 MUI/day). A positive blood culture (n=5) was a prerequisite for administering colistin intravenously (4 MUI/day). Any potential toxicity was observed. The mean delay of extubation after starting treatment was 10 days. Sterile samples were obtained on average by the eighth day. No deaths were recorded.


It seems that aerosolized colistin is an important alternative to treat MRPA nosocomial pneumonia in ICU. Our results need further confirmation by other multicentre studies

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September 1, 2011 at 11:35 pm Leave a comment

Unlabeled Uses of Nebulized Medications: Colistin


American Journal of Health-System Pharmacy. 2006 V.63 N.18 P.1704-1716

One of the greatest concerns among several patient populations is chronic pulmonary infection with Pseudomonas and other gram-negative bacteria. These organisms can be difficult to treat as resistant strains commonly develop, and treatment-related toxicities present a concern. This has led researchers to look for alternatives in patients with gram-negative pulmonary infections. Nebulized colistin sulfomethate, or polymyxin E, is used increasingly to manage Pseudomonas infections in cystic fibrosis patients. InEurope, nebulized colistin is commonly used in long-term management of Pseudomonas. I.V. colistin had been used to treat a variety of bacteria but became less common because of its nephrotoxicity and neurotoxicity and the development of safer antimicrobials.

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September 1, 2011 at 11:34 pm Leave a comment

Nebulized Colistin in the Treatment of Pneumonia Due to Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa

CID Sept.1, 2005  V.41  • BRIEF REPORT

Andrea L. H. Kwa,1 ChinSiew Loh,1 Jenny G. H. Low,2 Asok Kurup,2 and Vincent H. Tam3

1Department of Pharmacy and  2Department of Internal Medicine, Division of Infectious Diseases, Singapore General Hospital, Singapore; and 3University of Houston College of Pharmacy, Houston, Texas

Twenty-one patients with multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa pneumonia were treated with nebulized polymyxin E (colistin). Overall clinical and microbiological response rates were 57.1% and 85.7%, respectively. Nebulized colistin may be reasonably efficacious and safe for treatment of MDR pneumonia. Its role in therapy warrants further investigation in comparative studies.


September 1, 2011 at 11:32 pm Leave a comment


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