Efficacy of High-dose Nebulized Colistin in Ventilator-associated Pneumonia Caused by Multidrug-resistant Pseudomonas aeruginosa  and Acinetobacter baumannii

Lü, Qin; Luo, Rubin; Bodin, L.; Yang, Jing; Zahr, Noël; Aubry, Alexandra; Golmard, Jean‐Louis; Rouby, Jean‐Jacques

doi:10.1097/aln.0b013e31827515de

Cited by 189 publications

(136 citation statements)

References 57 publications

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“…Thus, at this point, the data are mixed regarding whether adding inhaled colistin to systemic therapy improves clinical cure. Importantly, several studies have reported favorable outcomes of patients with ventilator-associated pneumonia caused by highly resistant Gram-negative bacteria, including XDR A. baumannii, treated with monotherapy inhalational colistin without adjunctive systemic therapy (255,259,261,263). However, these results should be viewed cautiously, as cases were nonrandomized leading to a potential selection bias.…”

Section: Current Treatment Optionsmentioning

confidence: 58%

“…In contrast, nebulizing polymyxins has the potential to achieve very high concentrations in the lungs while minimizing systemic exposure and toxicity. Numerous investigators have described favorable outcomes of patients with nonbacteremic Acinetobacter pneumonia who were treated with nebulized polymyxins (252)(253)(254)(255)(256)(257)(258)(259)(260)(261). In one case-control study, use of inhaled colistin increased microbial eradication rate from the airways in ventilated patients compared to systemic therapy (257).…”

Section: Current Treatment Optionsmentioning

confidence: 99%

“…Furthermore, resistance has emerged during therapy, although with variable frequency depending on the case series (255,261,263).…”

Section: Current Treatment Optionsmentioning

confidence: 99%

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Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

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Section: Current Treatment Optionsmentioning

confidence: 58%

Section: Current Treatment Optionsmentioning

confidence: 99%

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Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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“…However, concentrations of formed colistin in the ultrafiltrate were similar at the beginning and end of sampling. Additionally, the patients were treated with nebulized CMS during CVVH and pharmacokinetic sampling, which may complicate the interpretation of colistin plasma concentrations, but inhaled colistin has been shown to have minimal systemic absorption at doses higher than those observed here (31,32). Due to the inherent limitations in the system of care at the U.S. Army Institute of Surgical Re- search, we were not able to ascertain the age of the CVVH filters at the time of sampling.…”

Section: Discussionmentioning

confidence: 99%

Colistin Pharmacokinetics in Burn Patients during Continuous Venovenous Hemofiltration

Akers

Rowan

Niece

et al. 2015

Antimicrob Agents Chemother

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e While colistin is considered a last resort for the treatment of multidrug-resistant Gram-negative bacterial infections, there has been an increase in its use due to the increasing prevalence of drug-resistant infections worldwide. The pharmacology of colistin is complex, and pharmacokinetic data are limited, especially in patients requiring renal replacement therapy. As a result, dosing for patients who require renal replacement remains a challenge. Here, we present pharmacokinetic data for colistin from two burn patients (37 and 68 years old) infected with colistin-susceptible isoclonal Acinetobacter baumannii and receiving continuous venovenous hemofiltration (CVVH). To our knowledge, we are the first to examine data from before and during CVVH (for one patient), allowing analysis of the effect of CVVH on colistin pharmacokinetics. Pharmacokinetic/pharmacodynamic analysis indicated that a dose increase from 1.5 to 2.2 mg/kg of body weight colistin base activity on CVVH was insufficient to satisfy the target parameter of an AUC 24 /MIC (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of >60 at an MIC of >1 g/ml in one patient with residual endogenous renal function. Plasma concentrations of colistin ranged from 0 to 15 g/ml, with free colistin levels ranging from 0.4 to 2.2 g/ml. While both patients resolved their clinical infections and survived to discharge, colistin-resistant colonizing isolates resulted from therapy in one patient. The variabilities observed in colistin concentrations and pharmacokinetic characteristics highlight the importance of pharmacokinetic monitoring of antibiotics in patients undergoing renal replacement therapy.

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“…In the largest, most well-designed cohort to date, 28 patients with VAP due to MDR A. baumannii or P. aeruginosa were treated with inhaled colistin monotherapy in a prospective, observational study (284). These patients were compared to those with MDR VAP treated with inhaled colistin along with an i.v.…”

Section: Nosocomial Pneumoniamentioning

confidence: 99%

Inhaled Antibiotics for Gram-Negative Respiratory Infections

et al. 2016

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SUMMARYGram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects,in vitroand microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

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Efficacy of High-dose Nebulized Colistin in Ventilator-associated Pneumonia Caused by Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii

Cited by 189 publications

References 57 publications

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Colistin Pharmacokinetics in Burn Patients during Continuous Venovenous Hemofiltration

Inhaled Antibiotics for Gram-Negative Respiratory Infections

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