Acinetobacter baumannii

Why this is important:

Acinetobacter spp. are increasingly recognised as a cause of hospital-acquired outbreaks, particularly in the ICU setting. Here in the UK, it has been a particular problem in London. These organsims represent a particular infection control problem, in the most vulnerable in-patients. Their ability to survive dry environmental conditions and to acquire resistance to a wide range of antimicrobial agents has recently increased the awareness of these important pathogens. These organisms cause invasion at any site. We will examine the microbiology, pathogenicity and therapeutic options.

History:

• 30-40 years ago: 70% ampicillin, 97% carbenicillin sensitive.
• 1971: 41% ampicillin (in ICU), 80% gentamicin sensitive.
• In the 1970's a growing number of β-lactamases & aminoglycosidases.
• 1980's: >90% ceftazidime, >95% ciprofloxacin sensitive.
• 1984: Mutation (acquired via plasmids & point mutations) lead to ciprofloxacin resistance.
• 1985: Major resistance developed to all antibiotics except imipenem, tobramycin, amikacin & ceftazidime.
• 2000: 85% of isolates resistant to cephalsporins, 50% to gent, 20% to amikacin, 40% to tazocin.
• 2002: 30 Hospital ICU outbreak of Acinteobacter baumannii
• Increasing incidence of SE clone: variable resistance to imipenem, sensitive to colistin
• OXA-23 clone (1) noted to be resistant to imipenem, sensitive to minocyline
• OXA-23 clone (2) has an increased resistance antibiogram: sensitive only to amikacin

Microbiology:

Acinetobacter spp. are:

• Rod shaped during rapid growth and coccobacillary in the stationary phase.
• Encapsulated (generally).
• Nonmotile (although they may exhibit twitching motility).
• Gram-negative organisms. Retention of crystal violet may result in incorrect identification as gram-positive cocci.
• Indole negative.
• Catalase positive.
• They are oxidase negative (opposite to Neisseria spp. or Moraxella spp.)
• Haemolytic.
• able to acidify glucose (may enhance its ability to invade devitalized tissue).
• Grow at 44° C.
• Aerobic.
• Acinetobacter spp have the ability to use various sources of nutrition which accounts for its growth on routine laboratory media. This also explains its survival as an environemental pathogen.
• Colonies are 1 to 2 mm, nonpigmented, domed, and mucoid, with smooth to pitted surfaces.
• They can't reduce nitrate or to grow anaerobically (different from Enterobacteriaceae).

Mechanisms for resistance to carbapenems:

• metallo-β-lactamse (VIM, IMP): gene transfer, gene activation my insertion of an activation sequence (this is inserted upstream and switches on enzyme production) & mutation.
• OXA carbapenemases (class D) - difficult to detect.
• cell permeability changes.
• target (PBPs) change.

Metallo-β-lactamses:

• Common in the Far East, rare in Europe.
• Various VIM & IMP types (plasmid mediated).
• Extracts have been shown to hydrlyse imipenem.
• High incidence in Pseudomonas aeuroginosa referred to the HPA.

Pathogenicity:

Lipopolysaccharide is present in the cell wall, but little is known of its endotoxigenic potential in humans, and Acinetobacter only becomes pathogenic when the host defences are disrupted. Acinetobacter infection can occur in any body site. Reported ocular cases include conjunctivitis, endophthalmitis, corneal ulceration due to soft contact lens contamination, and corneal perforation. Native and prosthetic valve endocarditis has been described. Osteomyelitis, septic arthritis, and pancreatic and liver abscesses have also been reported. Acinetobacter baumanii has been associated with various nosocomial infections including:

Risk factors include:

Treatment:

Increasing antibiotic resistance has been a problem. Documented mechanisms of resistance include:

Resistance has been tracked to plasmids, transposons, and chromosomes. Most A. baumannii are now resistant to ampicillin (~91% resistant to gentamicin). Resistance to tobramycin and amikacin is increasing. Ertapenem, the newest of the carbapenems, has little intrinsic activity against Acinetobacter and should not be used. Increasing resistance to quinolones, aminoglycosides carbapenems have been a problem in the UK and elsewhere. Locally, the two isolates found were only sensitive to colistin and amikacin, this is in keeping withe the sensitivity profile of the London isolates. Intravenous colistin (polymyxin B) has been used successfully against carbapenem-resistant Acinetobacter, despite concerns raised by animal model data. The literature does not favor the use of colistin to treat A. baumannii pneumonia, even though in vitro studies using MICs have suggested that it is the most active alternative. This is in part due to poor clearance of the pathogen from the blood and lungs of mice (although the results of experimental infections require careful interpretation and any extrapolation to humans should be made with great caution!). Resistance has been identified to polymyxin B. Imipenem or meropenem with an aminoglycoside and β-lactam/β-lactamase inhibitor with an aminoglycoside (+/- rifampacin) were found to be synergistic in vitro against multidrug-resistant nosocomial A. baumannii isolates. Many mild to moderately severe infections respond to monotherapy with an active agent. The current approach to treating a serious, deep-seated infection involving Acinetobacter should be based on sensitivities of the specific isolate and the use of combination therapy. If using β-lactams, be aware of therapeutic failures and due to emerging resistance. Imipenem or meropenem has been used successfully alone and in combination with a 4-fluoroquinolone, rifampin, colistin (polymyxin B) or an aminoglycoside. Intravenous colistin compared favorably to imipenem in one small study treating multidrug-resistant Acinetobacter ventilator-associated pneumonia. Local isolates were not treated in one case, and the other patient had amikacin. Colistin is used in CF patients usually in 2mU doses (either IV or nebulised).

And finally...

A hospital outbreak involving multidrug-resistant Acinetobacter strains with a similar antibiogram should prompt a review of infection control procedures involving hand washing, patient isolation, ventilator care, and ward hygeine. It may also require a local review of prescribing practices as some ICUs use a lot of tazocin & imipenem. The use of nonabsorbable antibiotics for selective decontamination of the digestive tract has been suggested in some cases.

AMH