遭遇すると ヒヤリ Acinetobacter
Acinetobacter has the ability to develop resistance through several diverse mechanisms, leading to the emergence worldwide of drug-resistant strains, which are more difficult to treat and are associated with a higher mortality than susceptible strains. Healthcare exposures, including prior antibiotic receipt (particularly carbapenems and fluoroquinolones), are associated with colonization and infection due to drug-resistant isolates.
Most support for the use of various antibiotics for Acinetobacter infections is based upon in vitro data and observational series. Very few trials have evaluated the efficacy and safety of different antimicrobial regimens for Acinetobacter infections. When infections are caused by antibiotic-susceptible Acinetobacter isolates, there may be several therapeutic options, including a broad-spectrum cephalosporin (ceftazidime or cefepime), a combination beta-lactam/beta-lactamase inhibitor (ie
, one that includes sulbactam), or a carbapenem (eg, imipenem, meropenem, or doripenem). In the setting of resistance to the above agents, therapeutic options are polymyxins and possibly tigecycline.
Empiric antibiotic therapy for Acinetobacter, before results of antimicrobial susceptibility testing are available, should be selected based on local susceptibility patterns. In general, it should consist of a broad spectrum cephalosporin, a combination beta-lactam/beta-lactamase inhibitor (eg, a combination including sulbactam), or a carbapenem. For empiric therapy of patients with Acinetobacter infection in a location where resistance to the chosen antibiotic is high, we suggest addition of a second agent pending susceptibility results (Grade 2C). An antipseudomonal fluoroquinolone, an aminoglycoside, or colistin are second agent options.
Once results of antimicrobial susceptibility testing are available, a regimen can be chosen from among the active agents. We favor choosing the agent with the narrowest spectrum of activity. For patients with infections due to extensively drug-resistant Acinetobacter, therapeutic options are generally limited to polymyxins (colistin, or polymyxin E, and polymyxin B), minocycline, and tigecycline. For such patients, we suggest using a second agent in addition to one of these (Grade 2C).
Because of the possibility
of emergent resistance to antibiotics during therapy, continued monitoring of the patient for clinical worsening following initial improvement is important.
Adequate management of Acinetobacter infections also includes removal of associated foreign material, such as urinary or venous catheters. In patients who have Acinetobacter pneumonia resistant to beta-lactams and carbapenems and thus receive an alternate intravenous antibiotic, we suggest inhaled colistin as adjunctive therapy (Grade 2C). Variable cerebrospinal fluid (CSF) penetration of antibiotic agents further limits the therapeutic choices for Acinetobacter central nervous system (CNS) infections, for which higher doses of antibiotics is generally warranted. Additional considerations include the possible use of intrathecal antibiotics for drug-resistant isolates and the removal of CNS devices, if present.
Prevention of drug-resistant Acinetobacter depends on early recognition, aggressive control of spread, and preventing establishment of endemic strains. Drug-resistant Acinetobacter remains largely susceptible to disinfectants and antiseptics.
Independent risk factors for colonization or infection with resistant strains of Acinetobacter include the following:
- prior colonization with methicillin-resistant Staphylococcus aureus (MRSA)
- prior beta-lactam use, particularly carbapenems
- prior fluoroquinolone use
- bedridden status
- current or prior intensive care unit admission
- presence of a central venous catheter
- recent surgery
- mechanical ventilation
Acinetobacter species are capable of accumulating multiple antibiotic resistance genes, leading to the development of multidrug-resistant or extensively drug-resistant strains. Frequently expressed resistance mechanisms in nosocomial strains of Acinetobacter include beta-lactamases, alterations in cell-wall channels (porins) and efflux pumps:
AmpC beta-lactamases are chromosomally encoded cephalosporinases intrinsic to all Acinetobacter baumannii. Usually, such beta-lactamases have a low level of expression that does not cause clinically appreciable resistance; however, the addition of a promoter insertion sequence ISAba1 next the ampC gene increases beta-lactamase production, causing resistance to cephalosporins.
The most troubling clinical resistance mechanism has been Acinetobacter’s acquisition of beta-lactamases, including serine and metallo-beta-lactamases, which confer resistance to carbapenems. Acquired extended-spectrum beta-lactamase carriage occurs in Acinetobacter but is not as widespread as in Klebsiella pneumoniae or Escherichia coli.
Porin channels in A. baumannii are poorly characterized; it is known that reduced expression or mutations of bacterial porin proteins can hinder passage of beta-lactam antibiotics into the periplasmic space, leading to antibiotic resistance.
Overexpression of bacterial efflux pumps can decrease the concentration of beta-lactam antibiotics in the periplasmic space. To cause clinical resistance in Acinetobacter, efflux pumps usually act in association with overexpression of AmpC beta-lactamases or carbapenemases. Efflux pumps can remove beta-lactam antibiotics as well as quinolones, tetracyclines, chloramphenicol, and tigecycline.
A. baumannii can become resistant to quinolones through mutations in the genes gyrA and parC, and can become resistant to aminoglycosides by expressing aminoglycoside-modifying enzymes.
The mechanism of resistance of Acinetobacter to colistin appears to be associated with a mutation in the genes encoding the PmrA and B proteins; additional regulatory factors remain to be determined.
Heteroresistance, characterized by resistant subpopulations within a single strain, has been described in Acinetobacter strains.