Acinetobacter Pneumonia: A Review

Joshua D. Hartzell, MD, Andrew S. Kim, MD, Mark G. Kortepeter, MD, MPH, Kimberly A. Moran, MD

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In This Article

Treatment

There are no randomized, controlled trials (RCTs) comparing antimicrobial therapy for pneumonia caused by Acinetobacter species, but retrospective and prospective therapeutic observational studies have been published. Most recent literature on the topic describes use of polymyxin B or E (colistin) (intravenous, intramuscular, or inhaled) for treatment of Abc. This is largely because some nosocomial isolates are only susceptible to colistin due to increasing resistance. A prospective study comparing the efficacy of treatment of multidrug-resistant Abaumannii VAP with intravenous colistin vs imipenem showed no differences in clinical cure, in-hospital mortality rates, or toxicity.[70] In a comprehensive review of the published literature on use of polymyxins to treat critically ill patients, Falagas and colleagues showed the utility of these agents; however, they emphasized judicious use of polymyxins to prevent drug resistance.[71] Risk for nephrotoxicity was also highlighted. Several studies have found less colistin-associated nephrotoxicity than originally reported; nevertheless, focus should remain on appropriate dosing and close monitoring of renal function due to this potential complication.[72,73,74,75,76]

Use of inhaled colistin has been reported for over 30 years, but interest in its use has dramatically increased along with emergence of multidrug-resistant Abc and Pseudomonas aeruginosa.[77,78,79,80,81] Current knowledge about inhaled colistin derives mainly from use in patients with cystic fibrosis. More recent reports have examined the benefit of this therapy in patients without cystic fibrosis, and despite a clear lack of data regarding dosing, efficacy, and safety from RCTs, colistin is being used clinically for treatment of multidrug-resistant Abc.[82,83,84]

Small case series have demonstrated clinical improvement when inhaled colistin has been used as adjunctive therapy for multidrug-resistant Abc HAP or VAP.[67,82,83,84] The largest retrospective series to date reported 71 patients, including 47 with Abc pneumonia, treated with inhaled colistin (monotherapy in 9 cases).[84] The mean duration of therapy was 12 ± 8 days. None of the 33 patients with Abc pneumonia assessed for microbiologic cure had positive follow-up cultures.

The exact pharmacokinetics, pharmacodynamics, and optimal dosing regimens for aerosolized colistin remain unclear. Manufacturer recommended doses range from 40-80 mg (500,000-1 million units) every 12 hours depending on weight, but in published reports providers have used varied dosing and frequency regimens.[67,82,83,84]

Administration of inhaled aminoglycosides as an adjunct to systemic treatment for gram-negative VAP has not been extensively considered in the literature, despite favorable pharmacokinetic and patient tolerance profiles.[85] In a recent pilot study, Hallal and colleagues compared a 14-day course of aerosolized tobramycin plus an intravenous beta-lactam antibiotic with a 14-day course of an intravenous beta-lactam plus intravenous tobramycin for treatment of P aeruginosa or Abc VAP; they found a survival benefit in the inhaled tobramycin group.[86] To date, there are no published data on inhaled aminoglycosides for multidrug-resistant Abc VAP.

Because drug resistance is increasing and there are no new antibiotics in development for treatment of multidrug-resistant gram-negative bacteria, there is growing interest in pharmacokinetic and pharmacodynamic principles to combat these pathogens and prevent further development of resistance. Mattoes and coworkers, following an extensive review, reported that meropenem pharmacodynamics for susceptible pathogens could be optimized by using higher doses, increasing dosing frequency, or prolonging the duration of infusion.[87] Li and colleagues used a population pharmacokinetic model to demonstrate that prolonged meropenem infusion time (3 hours) resulted in increased probability of achieving the target mean inhibitory concentration or Enterobacteriaceae, Acinetobacter species, and P aeruginosa.[88] Novel strategies, including increased dosing and infusion times of available time-dependent killing antibiotics, must be considered to optimize therapeutics for multidrug-resistant bacteria.

Combination therapy for treatment of multidrug-resistant Abc pneumonia remains controversial. Saballs and colleagues evaluated the efficacy of combination therapy with rifampin and imipenem in carbapenem-resistant Abc infections based on success in a mouse model.[89] However, because of therapeutic failures, the authors recommended against this combination for carbapenem-resistant Abc. Lee and coworkers retrospectively compared combination therapy of "pan-drug resistant" A baumannii with a carbapenem plus sulbactam vs other antibiotics (eg, cephalosporins, fluoroquinolones) plus an aminoglycoside.[90] The combination of carbapenem and sulbactam lowered mean inhibitory concentrations for many of the isolates; however, no significant difference in outcomes was seen between the 2 groups. Falagas and colleagues retrospectively compared treatment of multidrug-resistant gram-negative infections with colistin alone vs colistin combined with meropenem.[76] No significant differences in clinical response or nephrotoxicity were observed. In vitro and animal studies have shown synergistic antibiotic combinations against Abc; however, no formal RCTs to assess clinical efficacy have been done.[91,92,93]

Therapy for pneumonia caused by Abc should be based on susceptibility results. However, pending microbiologic data, empirical antibiotic therapy should be chosen based on the most likely offending pathogens and the local antibiogram. Dual empirical therapy (2 parenteral agents or 1 parenteral agent and 1 inhaled agent) should be considered in critically ill patients who are likely to be infected with a multidrug-resistant pathogen.

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