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   Table of Contents     
LETTER TO EDITOR  
Year : 2016  |  Volume : 8  |  Issue : 3  |  Page : 125-126
Polymyxin-B combination therapy - A dire need to safeguard our last hope


1 Consultant - Internal Medicine and Infectious Diseases, Columbia Asia Hospital, Pune, Maharashtra, India
2 Glenmark Pharmaceuticals Ltd., Mumbai, Maharashtra, India

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Date of Web Publication17-Aug-2016
 

How to cite this article:
Lakhe M, Patil SV, Korukonda K, Bhargava A. Polymyxin-B combination therapy - A dire need to safeguard our last hope. J Global Infect Dis 2016;8:125-6

How to cite this URL:
Lakhe M, Patil SV, Korukonda K, Bhargava A. Polymyxin-B combination therapy - A dire need to safeguard our last hope. J Global Infect Dis [serial online] 2016 [cited 2020 Aug 6];8:125-6. Available from: http://www.jgid.org/text.asp?2016/8/3/125/188599


Sir,

We report a case of ventilator-associated pneumonia caused by extensive drug resistant (XDR) Pseudomonas aeruginosa managed effectively by polymyxin-B and doripenem combination.

A 34-year-old, nonsmoker male, from Pune, was transferred to our department from other hospital with a clinical diagnosis of hospital-acquired pneumonia with underlying respiratory failure. He was receiving treatment for H1N1 pneumonitis, where he clinically worsened and transferred to another hospital before shifting to our setup, where high-resolution computed tomography (HRCT) was performed which showed the bilateral dense multilobar shadow. He has received meropenem (500 mg q8 h) and amikacin (500 mg OD) for 5 days.

During admission to our department, he was in acute respiratory distress syndrome (ARDS), already tracheostomized, mechanically ventilated with fever (38.8°C) and leukocytosis (32,000/mm 3 ). His serum creatinine was 1.4 mg/dl started empirically on meropenem (1 g q8 h) as 30 min infusion and vancomycin (1 g q12 h). We immediately performed a fiberoptic bronchoalveolar lavage in all the involved pulmonary lobes and an MDR P. aeruginosa >10 5 CFU/mL was isolated in every sampled pulmonary site. This strain was susceptible only to colistin as per Vitek-2 report. E-test was asked for meropenem, doripenem, and colistin. Minimum inhibitory concentration (MIC) values were 1, 8, and 16 mg/L for colistin, doripenem, and meropenem, respectively.

We changed the antibiotic therapy in patient to intravenous polymyxin-B 7.5 lakh units 12 hourly and doripenem 1 g 8 hourly as 4 h infusion.

The patient became afebrile on day 3 and sustained defervescence was observed after 7 days. He was weaned off ventilator support on day 4, continued on polymyxin-B and doripenem for 14 days. Repeat HRCT was performed on day 13 post hospital admission which showed bilateral resolution of shadows. Serum creatinine on day 14 of polymyxin therapy was 1.2 mg/dl. After 10 days of stay in our intensive care unit, the patient was transferred to a ward where, after 5 days, he was discharged to his home. No adverse events were reported; in particular, nephrotoxicity was not observed.

We used polymyxin-B and doripenem combination therapy based on the results published by Rigatto et al. which showed that the combination of polymyxin-B with carbapenem lacking in vitro activity, was able to significantly reduce the risk of mortality in critically ill patients infected by XDR Acinetobacter baumannii or P. aeruginosa. [1] The choice of doripenem over meropenem was driven by the E-test report which showed lower MIC value for doripenem.

The pharmacokinetic edge of polymyxin-B over colistin and renal independent dosing is well understood in recent literature, which influenced our choice of combination therapy. [2]

Cheah et al. recently showed the importance of adaptive resistance in bacterial regrowth during polymyxin treatment and recognized the role of combination regimen as most promising option for reducing the emergence of polymyxin resistance. [3]

Gomez et al. reported clinical improvement with doripenem and polymyxin-B combination therapy in complicated urinary tract infection with secondary bacteremia. [4]

Recently, Ly et al. evaluated the pharmacodynamics of polymyxin-B with doripenem against P. aeruginosa to determine the usefulness of the combinations. [5] Results showed killing activity against all strains by the combination, also complete eradication observed at concentrations of > 4 mg/L and 8 mg/L for polymyxin-B and doripenem, respectively. [5]

We believe the good clinical response observed in our case was due to in vivo synergy of polymyxin-B and doripenem suppressing the regrowth of heteroresistant subpopulation resulting in more potent microbiological action.

It should also be emphasized that we used polymyxin-B as per current dosing recommendations.

In conclusion, there is increasing evidence to support the use of combination therapy in carbapenem-resistant organisms, but there are many unanswered questions. Further, this combination can be evaluated by in vitro demonstration of enhanced killing by polymyxin-B-based combination with doripenem against XDR P. aeruginosa. Furthermore, setting up in vitro hollow-fiber and in vivo animal infection models with the proposed combination regimens will translate these dosing strategies to patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Rigatto MH, Vieira FJ, Antochevis LC, Behle TF, Lopes NT, Zavascki AP. Polymyxin B in combination with antimicrobials lacking in vitro activity versus polymyxin B in monotherapy in critically Ill patients with Acinetobacter baumannii or Pseudomonas aeruginosa infections. Antimicrob Agents Chemother 2015;59:6575-80.  Back to cited text no. 1
    
2.
Akajagbor DS, Wilson SL, Shere-Wolfe KD, Dakum P, Charurat ME, Gilliam BL. Higher incidence of acute kidney injury with intravenous colistimethate sodium compared with polymyxin B in critically ill patients at a tertiary care medical center. Clin Infect Dis 2013;57:1300-3.  Back to cited text no. 2
    
3.
Cheah SE, Li J, Tsuji BT, Forrest A, Bulitta JB, Nation RL. Colistin and polymyxin B dosage regimens against Acinetobacter baumannii: Differences in activity and the emergence of resistance. Antimicrob Agents Chemother 2016;11: AAC-02927-15.  Back to cited text no. 3
    
4.
Gomez E, Sanchez M, Gul Z, Urban C, Mariano N, Eng RH, et al. Polymyxin combination therapy and the use of serum bactericidal titers in the management of KPC-producing Klebsiella pneumoniae infections: A report of 3 cases. Case Rep Med 2011;2011:659769.  Back to cited text no. 4
    
5.
Ly NS, Bulman ZP, Bulitta JB, Baron C, Rao GG, Holden PN, et al. Optimization of polymyxin B in combination with doripenem to combat mutator Pseudomonas aeruginosa. Antimicrob Agents Chemother 2016;60:2870-80.  Back to cited text no. 5
    

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Correspondence Address:
Dr. Saiprasad Vilas Patil
Glenmark Pharmaceuticals Ltd., Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-777X.188599

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