Inhaled colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria: A real-life experience in tertiary care hospitals in Saudi Arabia

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Abstract

Background

Nosocomial pneumonia (NP) due to multidrug-resistant (MDR) Gram-negative pathogens, has continued to rise over the last several decades. Parenteral administration of colistin results in poor alveolar penetration and subtherapeutic concentration; therefore, direct drug deposition at site of infection may improve the effectiveness while minimizing the systemic exposure. The aim of this study is to describe the safety and effectiveness of inhaled colistin for the treatment of NP caused by MDR Gram-negative pathogens.

Method

Patients who received inhaled colistin from May 2015 to May 2019 at 2 different tertiary care hospitals in Riyadh, Saudi Arabia were identified from pharmacy databases and their charts were retrospectively reviewed.

Results

86 patients were enrolled in this study. The mean age was 56 ± 20 years. The mean Acute Physiology and Chronic Health Evaluation (APACHE II) was 17 ± 5. The responsible pathogens for NP were Pseudomonas aeruginosa (60%) Acinetobacter baumannii (28%), and Klebsiella pneumoniae (9%). Most patients (76/86) received concomitant intravenous antibiotics. Mean colistin total daily dose was 6 ± 3 million international units divided into 2–3 doses. Mean inhaled colistin duration of therapy was 11 ± 6 days. Favorable clinical outcome was achieved in 51 (59%) patients while favorable microbiological outcome occurred in 29 (34%) patients. Death due to all causes was noted in 39 (45%) cases. Renal injury occurred in 19 (22%) patients, all received concomitant intravenous colistin.

Conclusion

Inhaled colistin can be considered as salvage therapy as adjunct to intravenous administration for treatment of patients with NP due to MDR Gram-negative pathogens.

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Most cited references 15

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Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections.

Matthew E. Falagas, Sofia Kasiakou (2005)

The emergence of multidrug-resistant gram-negative bacteria and the lack of new antibiotics to combat them have led to the revival of polymyxins, an old class of cationic, cyclic polypeptide antibiotics. Polymyxin B and polymyxin E (colistin) are the 2 polymyxins used in clinical practice. Most of the reintroduction of polymyxins during the last few years is related to colistin. The polymyxins are active against selected gram-negative bacteria, including Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species. These drugs have been used extensively worldwide for decades for local use. However, parenteral use of these drugs was abandoned approximately 20 years ago in most countries, except for treatment of patients with cystic fibrosis, because of reports of common and serious nephrotoxicity and neurotoxicity. Recent studies of patients who received intravenous polymyxins for the treatment of serious P. aeruginosa and Acinetobacter baumannii infections of various types, including pneumonia, bacteremia, and urinary tract infections, have led to the conclusion that these antibiotics have acceptable effectiveness and considerably less toxicity than was reported in old studies.

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Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score.

A. de Mendonca, J-L Vincent, P Suter … (2000)

To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. Prospective, multicenter, observational cohort analysis. Forty ICUs in 16 countries. All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. Of the patients, 348 (24.7%) developed ARF, as diagnosed by a serum creatinine of 300 micromol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p < 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8% vs 14.0%, p < 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95%: 1.23-2.06], p < 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.

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Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration.

Roberto Imberti, Maria Cusato, Paola Villani … (2010)

Infections caused by multidrug-resistant gram-negative bacteria have caused a resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients, and no attempts have been made to evaluate its concentration in BAL. In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulfonate (CMS) IV, 2 million International Units (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 h. Colistin was measured by a selective, sensitive high-performance liquid chromatography-based method. Pharmacokinetic parameters were determined by noncompartmental analysis. Patients received 2.19 ± 0.38 mg/kg (range, 1.58-3.16) of CMS per dose. At steady state, mean ± SD plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21 ± 1.08 and 1.03 ± 0.69 μg/mL, respectively. Mean ± SD area under the plasma concentration-time curve from 0 to 8 h (AUC(0-8)), apparent elimination half-life, and apparent volume of distribution were 11.5 ± 6.2 μg × h/mL, 5.9 ± 2.6 h, and 1.5 ± 1.1 L/kg, respectively. Cmax/minimum inhibitory concentration (MIC) ratio and AUC(0-24)/MIC ratio (MIC = 2 μg/mL) were 1.1 ± 0.5 and 17.3 ± 9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed. Although the pharmacodynamic parameters that better predict the efficacy of colistin are not known in humans, in critically ill adult patients the IV administration of CMS 2 million International Units (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin, which is undetectable in BAL. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen.

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Author and article information

Contributors

Thamer A. Almangour

Basel Alenazi

Leen Ghonem

Abdullah A. Alhifany

Bassam A. Aldakheel

Alya Alruwaili

Journal

Journal ID (nlm-ta): Saudi Pharm J

Journal ID (iso-abbrev): Saudi Pharm J

Title: Saudi Pharmaceutical Journal : SPJ

Publisher: Elsevier

ISSN (Print): 1319-0164

ISSN (Electronic): 2213-7475

Publication date PMC-release: 03 July 2020

Publication date (Print): August 2020

Publication date (Electronic): 03 July 2020

Volume: 28

Issue: 8

Pages: 1009-1013

Affiliations

[a ]Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

[b ]College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

[c ]Clinical Pharmacy Services, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia

[d ]Department of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, P.O. Box 13578, Makkah 21955, Saudi Arabia

[e ]Pharmacy Services Administration, King Fahad Medical City, P.O. Box. 59046, Riyadh 11525, Saudi Arabia

[f ]Clinical Pharmacy, Pharmacy Services Administration, King Fahad Medical City, P.O. Box. 59046, Riyadh 11525, Saudi Arabia

Author notes

[* ]Corresponding author. talmangour@ 123456ksu.edu.sa

Article

Publisher ID: S1319-0164(20)30149-3

DOI: 10.1016/j.jsps.2020.06.023

PMC ID: 7414068

PubMed ID: 32792845

SO-VID: 859359a4-bd57-47bf-bdda-dc2538dc75e2

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Inhaled colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria: A real-life experience in tertiary care hospitals in Saudi Arabia

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Pneumonia, sex, and the environment

Most cited references 15

Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections.

Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score.

Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration.

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