Acinetobacter Pneumonia: A Review

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

Disclosures
In This Article

Mechanisms of Antibiotic Resistance

A unique feature of Abc is rapid acquisition of antibiotic-resistance mechanisms. In the human host, these bacteria have transformed from largely susceptible 30 years ago to multidrug-resistant today.[44] Abs species utilize multiple mechanisms of resistance, and it is not uncommon for several mechanisms to exist within the same isolate ( Table 1 ). This has created new challenges for managing these infections. A recent review of this topic has been published.[45]

AmpC cephalosporinases, which are chromosomally encoded, are present in all strains of Abc.[46] AmpC is responsible for resistance to ceftazidime and other extended-spectrum cephalosporins. Multiple other beta-lactamases have also been reported in Abc and are described in detail in a recent paper.[45]

Integrons are mobile genetic elements that can carry multiple genes encoding for antibiotic resistance. It is important to note that they carry OXA beta-lactamases that confer resistance to carbapenems. They are also known to carry metalol-beta-lactamases, but these have been described mainly in Europe and Asia.[47,48,49,50] In addition to integrons, outer membrane protein changes can confer resistance to carbapenems.[45]

Molecular genetics now allows comparison of resistance phenotypes with genetic resistance markers.[46] Two studies illustrate the complicated genetic make-up responsible for the antibiotic resistance in Acinetobacter species. Hujer and colleagues provided genetic and phenotypic data on 75 distinct isolates from WRAMC.[46] They reported that 89% of the isolates were resistant to 3 or more classes of antibiotics. A total of 15% of isolates was resistant to 9 antibiotics (5 classes) tested. Over 90% of isolates were resistant to ciprofloxacin, and at least 80% were resistant to extended-spectrum cephalosporins. Twenty percent of isolates were resistant to imipenem and 24% to meropenem. This discordance between imipenem and meropenem sensitivity has been reported previously.[51] The Hujer study identified 16 resistance genes and 4 mobile genetic elements.[46]

Fournier and coworkers examined the genomic make-up of Acinetobacter resistance.[44] A study of a multidrug-resistant A baumannii strain (AYE) was compared with a fully susceptible strain (SDF),which identified the presence of an 86-kb resistance island that contained a cluster of 45 resistance genes in the AYE strain. The authors suggested that this island could be a "hotspot" that allows Acinetobacter to acquire resistance genes rapidly when under antibiotic pressure. Based on gene sequencing of the AYE strain, it appears that the organism has acquired most of its resistance genes from Pseudomonas, Salmonella, and Escherichia species.[44] The ability to develop multidrug resistance is becoming increasingly concerning because treatment options are limited.

Colistin is being used with rising frequency with the emergence of multidrug-resistant Abc. Not surprisingly, antibiotic resistance to colistin has been reported as well.[52,53,54] Beno and coworkers recently reported resistance data on 10 patients infected with 18 gram-negative bacilli isolates (2 with Abc) that were resistant to colistin.[52] They postulated that previous exposure to colistin and ciprofloxacin may have influenced the development of resistance. A previous abstract on an Israeli cohort of patients presented by Gilad and colleagues in 2005 also reported an association with colistin use and development of resistance.[53] While additional studies are needed, these trials suggest that using colistin alone may lead to future resistance.

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