A N T I M I C R O B I A L R E S I S TA N C E

INVITED ARTICLE

George M. Eliopoulos, Section Editor

Acinetobacter baumannii: Epidemiology, Antimicrobial

Resistance, and Treatment Options
Lisa L. Maragakis1,2 and Trish M. Perl1,2
1

Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, and 2Department of Hospital Epidemiology and Infection
Control, Johns Hopkins Medical Institutions, Baltimore, Maryland

Multidrug-resistant Acinetobacter baumannii is a rapidly emerging pathogen in the health care setting, where it causes infections that include bacteremia, pneumonia, meningitis, urinary
tract infection, and wound infection. The organisms ability to
survive under a wide range of environmental conditions and
to persist for extended periods of time on surfaces make it a
frequent cause of outbreaks of infection and an endemic, health
careassociated pathogen [1, 2].
EPIDEMIOLOGY
Risk factors for colonization or infection with multidrug-resistant Acinetobacter species include prolonged length of hospital stay, exposure to an intensive care unit (ICU), receipt of
mechanical ventilation, colonization pressure, exposure to antimicrobial agents, recent surgery, invasive procedures, and underlying severity of illness [1, 3]. Widespread environmental
contamination is often demonstrated, and outbreaks of infec-

Received 10 September 2007; accepted 8 December 2007; electronically published 13 March

2008.
Reprints or correspondence: Dr. Lisa L. Maragakis, Dept. of Hospital Epidemiology and
Infection Control, Johns Hopkins Hospital, 600 N. Wolfe St., Osler 425, Baltimore, MD 21287
(lmaraga1@jhmi.edu).
Clinical Infectious Diseases 2008; 46:125463
 2008 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2008/4608-0020$15.00
DOI: 10.1086/529198

1254 CID 2008:46 (15 April) ANTIMICROBIAL RESISTANCE

tion have been traced to respiratory care equipment, wound

care procedures, humidifiers, and patient care items [413].
Wilks et al. [8] reported a recent outbreak of multidrug-resistant Acinetobacter infection, with environmental contamination
found on curtains, laryngoscope blades, patient lifting equipment, door handles, mops, and keyboards. Medical equipment
has been implicated, emphasizing the need for special attention
to disinfection of shared items and extra caution with respiratory care and wound care procedures [4, 5, 7]. One or more
epidemic Acinetobacter clones often coexist with endemic
strains, making it difficult to detect and control transmission
[14, 15].
Table 1 outlines various infection control and prevention
methods for multidrug-resistant Acinetobacter infection. Investigators often report interruption of transmission after reinforcement of existing infection control and prevention standards, such as hand hygiene, standard precautions, barrier
precautions, and thorough environmental cleaning and disinfection [8, 16, 17]. Other transmission is more difficult to halt,
requiring cohorting of patients, dedicated staff assignments,
active surveillance cultures, and closure of entire ICUs [1113,
1823]. Most reports of successful control involve multiple
interventions, making it difficult to evaluate the efficacy of each
intervention individually [24]. Further investigation of the efficacy and cost-effectiveness of various infection control strat-

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Multidrug-resistant Acinetobacter baumannii is recognized to be among the most difficult antimicrobial-resistant gramnegative bacilli to control and treat. Increasing antimicrobial resistance among Acinetobacter isolates has been documented,
although definitions of multidrug resistance vary in the literature. A. baumannii survives for prolonged periods under a wide
range of environmental conditions. The organism causes outbreaks of infection and health careassociated infections, including
bacteremia, pneumonia, meningitis, urinary tract infection, and wound infection. Antimicrobial resistance greatly limits the
therapeutic options for patients who are infected with this organism, especially if isolates are resistant to the carbapenem
class of antimicrobial agents. Because therapeutic options are limited for multidrug-resistant Acinetobacter infection, the
development or discovery of new therapies, well-controlled clinical trials of existing antimicrobial regimens and combinations,
and greater emphasis on the prevention of health careassociated transmission of multidrug-resistant Acinetobacter infection
are essential.

Table 1.

Methods for control and prevention of multidrug-resistant Acinetobacter infection.

Method

Comments

Point source control

Standard precautions

Effective in the outbreak setting when a point source is identified

Includes hand hygiene, correct and consistent glove use, and appropriate use of
gowns and eye protection; reported compliance among healthcare personnel is
often poor

Contact barrier precautions

Includes dedicated patient care equipment and gowns and gloves for health care
personnel on entry to an isolation room

Environmental cleaning and disinfection

Widespread environmental contamination is often reported in the epidemic setting,

and environmental reservoirs likely play a role in the endemic setting as well

Cohorting of patients
Cohorting of health care personnel

Grouping colonized and infected patients into a designated unit or part of a unit
Designating staff to care for only patients colonized or infected with the organism

Clinical unit closure

Required in some outbreak settings to interrupt transmission and allow for thorough environmental disinfection

Antimicrobial stewardship

Programs to promote judicious antimicrobial use and prevent emergence of

resistance

Surveillance

Passive or active surveillance can identify infected or colonized patients so that interventions can be implemented

egies to prevent transmission of multidrug-resistant Acinetobacter infection are needed.

In addition to transmission, emergence of resistance occurs
in the context of selective pressure from broad-spectrum antimicrobial therapy, such as therapy involving carbapenems or
third-generation cephalosporins [25, 26]. The relative contributions of antimicrobial selective pressure and transmission
between patients on the emergence of multidrug-resistant Acinetobacter species are not known.
In many health care institutions, endemic, multidrug-resistant Acinetobacter infection demonstrates complex epidemiologic profiles and coexistence of multiple strain types. Abbo et
al. [27] studied 118 patients with multidrug-resistant Acinetobacter infection in Israel and found 10 different PFGE-typed
clones, as well as many small clusters of patients with no common source identified, despite molecular testing and extensive
investigation. Multidrug-resistant Acinetobacter infection has
been reported among patients residing in rehabilitation and
longterm care facilities, as well as in acute care hospitals [28,
29]. Several factors work together to maintain the presence of
multidrug-resistant Acinetobacter species in the health care setting, including the presence of susceptible patients, the presence
of patients already colonized or infected with the organism,
selective pressure from antimicrobial use, and incomplete compliance with infection control procedures [24] (figure 1).
Molecular-based strain typing by PFGE or other methods
can be used to identify outbreaks of infection and to monitor
interinstitutional, regional, and international transmission of
multidrug-resistant Acinetobacter species [30, 31]. Nemec et al.
[31] used ribotyping and amplified fragmentlength polymorphisms to demonstrate the genetic relatedness of Acinetobacter
isolates in western Europe. Investigators used PFGE to demonstrate interinstitutional spread of carbapenem-resistant Aci-

netobacter infection among acute care hospitals in locales including New York, Argentina, the United Kingdom, and the
Iberian Peninsula [3235]. Gales et al. [36] used PFGE to demonstrate the spread of epidemic Acinetobacter clones between
Brazil and Argentina.
Multidrug-resistant Acinetobacter deep wound infections, osteomyelitis, respiratory infections, and bacteremia have been
reported among military personnel with traumatic injuries during the conflicts in Iraq and Afghanistan [3740]. Theories that
previously colonized soldiers are autoinoculated or that Acinetobacter species from local soil or water are introduced during
traumatic injury have not been supported by cultures of specimens obtained from healthy soldiers, soil samples, water samples, or samples from fresh wounds [4144]. Current literature
suggests that these infections are associated with health care
and are acquired by soldiers in medical facilities during the
processes of stabilization, emergency treatment, and evacuation
through the military medical system [37, 39, 42, 43, 45, 46].
The potential for introduction of new, virulent, multidrugresistant Acinetobacter strains into hospitals by returning soldiers is a concern that warrants ongoing surveillance and careful
attention to infection control measures [39, 47, 48].
IMPACT ON PATIENT OUTCOMES
Because multidrug-resistant Acinetobacter infection usually occurs in severely ill patients in the ICU, the associated crude
mortality rate is high, ranging from 26% to 68% [4951]. It
has proven to be difficult, however, to determine the attributable mortality of these infections independent of patients
severe underlying illnesses. Recent studies and a systematic review concluded that Acinetobacter infection or colonization is
associated with increased mortality [5254]. Many of these
ANTIMICROBIAL RESISTANCE CID 2008:46 (15 April) 1255

Figure 1. Factors leading to the emergence and transmission of multidrug-resistant (MDR) Acinetobacter species. ICU, intensive care unit.

studies were limited by small sample sizes, methodological differences, and failure to adequately control for patients severity
of illness. Other studies that rigorously controlled for severity
of illness did not find Acinetobacter infection to be independently associated with increased mortality [1, 49, 55, 56]. An
alternative explanation is that Acinetobacter infection is a
marker of increased mortality in patients with severe underlying
illness but not an independent predictor of mortality [55].
Mortality may be related to the extent of antimicrobial resistance, the effectiveness of empirical therapy, and the availability of definitive therapeutic options. A recent matched cohort study from Korea found that administration of ineffective
empirical antimicrobial therapy for Acinetobacter bacteremia
was an independent predictor of 30-day mortality [51]. However, other studies have found poor correlation between patient
mortality and the empirical choice of antimicrobial agents to
which Acinetobacter infection was resistant [49, 55, 5759].
Acinetobacter infection is associated with increased morbidity
and a prolonged length of hospital stay. A retrospective,
matched cohort study found that patients with Acinetobacter
bacteremia had a 5-day excess length of mechanical ventilator
dependence and ICU stay, compared with critically ill patients
without Acinetobacter infection [56]. Multidrug-resistant Acinetobacter infection was found to significantly prolong the duration of ICU stay (by 6 days) and the median duration of
hospitalization (by 18 days) [49, 60]. One study found no
evidence of a prolonged length of ICU stay for patients with
Acinetobacter ventilator-associated pneumonia [61]. The impact on length of stay may depend on the type of infection and
the extent of antimicrobial resistance.
1256 CID 2008:46 (15 April) ANTIMICROBIAL RESISTANCE

ANTIMICROBIAL RESISTANCE
Antimicrobial resistance among Acinetobacter species has increased substantially in the past decade [62]. The capacity of
Acinetobacter species for extensive antimicrobial resistance may
be due in part to the organisms relatively impermeable outer
membrane and its environmental exposure to a large reservoir
of resistance genes [63]. Definitions of multidrug-resistant Acinetobacter species vary, referring to a wide array of genotypes
and phenotypes [64]. Two of the most common definitions of
multidrug resistance are carbapenem resistance or resistance to
3 classes of antimicrobials [64]. Some strains are susceptible
only to polymyxinspeptide antibiotics that are not routinely
used because of earlier reports about toxicities. Strains that
demonstrate resistance to all antimicrobial agents, including
polymyxins, have also been reported in the literature, making
treatment of these infections extremely difficult and in some
cases impossible [65, 66].
Mechanisms of resistance. Resistance mechanisms for Acinetobacter species are similar to those for Pseudomonas species,
although Acinetobacter species have not been studied as extensively [67, 68]. The mechanisms of resistance generally fall into
3 categories: (1) antimicrobial-inactivating enzymes, (2) reduced access to bacterial targets, or (3) mutations that change
targets or cellular functions [68]. For the first category, Acinetobacter species possess a wide array of b-lactamases that
hydrolyze and confer resistance to penicillins, cephalosporins,
and carbapenems. AmpC cephalosporinases are chromosomally
encoded and confer resistance to broad-spectrum cephalosporins [63, 67]. Recently, a large number of class D OXA-type

enzymes with activity against carbapenems were characterized

in locations that include Scotland, Spain, France, Japan, Singapore, China, Brazil, Cuba, and Kuwait [69, 70]. Some Acinetobacter strains express class B metallob-lactamases (MBLs),
such as VIM and IMP, which hydrolyze a broad array of antimicrobial agents, including carbapenems [67]. MBLs pose a
significant threat because they are often located on mobile genetic elements easily transferred among bacteria [63, 67]. Many
variants exist, and both IMP and VIM have been found worldwide in a wide array of bacterial species, including Acinetobacter
species [67, 71, 72].
Porin channels and other outer membrane proteins are important for transport of antimicrobial agents into the cell to
gain access to bacterial targets. Carbapenem resistance in Acinetobacter species has been linked to the loss of proteins thought
to be porin channels from the outer membrane [67, 73, 74].
It is likely that b-lactamases and outer-membrane alterations
work together to confer resistance to b-lactam agents [63].
Acinetobacter species possess efflux pumps that are capable of
actively removing a broad range of antimicrobial agents from
the bacterial cell [63].
The third category of resistance mechanisms involves point
mutations that alter bacterial targets or functions, decreasing
the affinity for antimicrobial agents or up-regulating cellular
functions, such as the production of efflux pumps or other
proteins. Resistance to colistin is thought to be mediated by
changes in the bacterial cell membrane that interfere with the
agents ability to bind bacterial targets [75]. This type of mechanism is also seen in Acinetobacter resistance to quinolone
agents from mutations in the bacterial targets gyrA and parC
topoisomerase enzymes [63].
Acinetobacter species can acquire resistance genes from other
organisms; mutations leading to resistance can develop over
time in Acinetobacter strains; or subpopulations with preexisting resistance may emerge and become dominant under antimicrobial selective pressure [69]. These 3 processes are not
mutually exclusive and likely function together to explain
emerging resistance among Acinetobacter species. A recent comparative genomic study of an epidemic, multidrug-resistant Acinetobacter strain in France found a large genomic resistance
island containing 45 resistance genes that appeared to have
been acquired from Pseudomonas, Salmonella, or Escherichia
genera [76]. The emergence of antimicrobial-resistant Acinetobacter species is due to both selective pressure exerted by the
use of broad-spectrum antimicrobials and transmission of
strains among patients, although the relative contributions of
these mechanisms are not yet known [14, 77].
TREATMENT
Carbapenems. Increasing antimicrobial resistance leaves few
therapeutic options, and there are no well-designed clinical

trials to compare treatment regimens for multidrug-resistant

Acinetobacter infection. Available data are from in vitro, animal,
and observational studies. Carbapenems remain the treatment
of choice if isolates retain susceptibility to this antimicrobial
class. The Meropenem Yearly Susceptibility Test Information
Collection (MYSTIC) surveillance program has documented
discordance that favors imipenem as the more potent agent,
compared with meropenem, for treatment of multidrug-resistant Acinetobacter infection [78, 79]. The converse result was
reported in Greece [80]. Efflux pumps may affect meropenem
to a greater degree, whereas specific b-lactamases hydrolyze
imipenem more efficiently [80]. Susceptibility testing of imipenem does not predict susceptibility to meropenem or vice
versa [78]. Unfortunately, carbapenem-resistant Acinetobacter
isolates are increasingly reported worldwide.
b-Lactamase inhibitors. b-Lactamase inhibitors, particularly sulbactam, have intrinsic activity against many Acinetobacter strains. The presence of a b-lactam agent (e.g., ampicillin)
in combination with the b-lactamase inhibitor does not appear
to contribute activity or synergy [81, 82]. Monotherapy with
sulbactam is not recommended for severe Acinetobacter infection. However, Wood et al. [83] reported successful use of
sulbactam to treat 14 patients with multidrug-resistant Acinetobacter ventilator-associated pneumonia, finding no difference
in clinical outcomes between sulbactam-treated patients and
63 patients who received imipenem. Levin et al. [84] reported
a cure rate of 67% using ampicillin-sulbactam to treat carbapenem-resistant Acinetobacter infection, but good patient outcomes were associated with lower severity of illness. The results
of antimicrobial susceptibility tests (e.g., with agar dilution or
the Etest) of blactam/b-lactamase combinations at fixed concentrations must be interpreted with caution, because they may
indicate susceptibility when an isolate is actually resistant [82].
Tigecycline. Tigecycline, a relatively new glycylcycline
agent, has bacteriostatic activity against multidrug-resistant Acinetobacter species [85, 86]. High-level resistance to tigecycline
has been detected among some multidrug-resistant Acinetobacter isolates, and there is concern that the organism can rapidly evade this antimicrobial agent by upregulating chromosomally mediated efflux pumps [68, 8791]. Peleg et al. [89]
reported 2 cases of multidrug-resistant Acinetobacter bacteremia
that occurred while patients were receiving tigecycline for another indication. Two recent studies documented overexpression of a multidrug efflux pump in Acinetobacter isolates with
decreased susceptibility to tigecycline [92, 93]. Given these findings and concern about whether adequate peak serum concentrations can be achieved, tigecycline is best reserved for salvage
therapy, with administration determined in consultation with
an infectious diseases specialist [89].
Aminoglycosides. Aminoglycoside agents, such as tobramycin and amikacin, are therapeutic options for infection with
ANTIMICROBIAL RESISTANCE CID 2008:46 (15 April) 1257

Table 2.

Studies of antimicrobial combinations against multidrug-resistant Acinetobacter infection.

Study

Year

Giamarellos-Bourboulis et al. [110]

2001

In vitro

Study method

Colistin and rifampin

Combination

In vitro synergy

Results/comments

Petrosillo et al. [111]

2005

Case series

Colistin and rifampin

Microbiologic cure in 64% of 14 patients

with VAP

Pantopoulou et al. [112]

2007

Animal study

Colistin and rifampin

Enhanced activity against experimental thigh

infection in neutropenic rats

Gleeson et al. [123]

2005

Case report

Meropenem and rifampin

Successful treatment of meningitis after meropenem monotherapy failed

Montero et al. [113]

2004

Animal study

Colistin and rifampin, imipenem and rifampin,

tobramycin and rifampin, imipenem and
tobramycin

The best regimens in a mouse pneumonia

model

Saballs et al. [114]

2006

Clinical pilot study

Imipenem and rifampin

Cautions against use of this regimen due to

high failure rate and emergence of rifampin
resistance in 70% of patients

Rodriguez-Hernandez et al. [115]

2000

Animal study

Imipenem and amikacin

Combination offered no advantage over imipenem monotherapy in a mouse pneumonia model

Bernabeu-Wittel et al. [116]

2005

Animal study

Imipenem and amikacin

Combination was worse than imipenem

alone in a guinea pig pneumonia model,
despite evidence of in vitro synergy

Haddad et al. [117]

2005

In vitro

Imipenem and amikacin; imipenem and

colistin

In vitro synergy

Ko et al. [118]

2004

Animal study

Meropenem and sulbactam

In vitro synergy and increased survival in a

mouse infection model

Kiffer et al. [119]

2005

In vitro

Meropenem and sulbactam

In vitro synergy

Sader et al. [122]

2005

In vitro

Cefipime and sulbactam

Kasiakou et al. [102]

2005

Case series

Colistin and another agent

Sobieszczyk et al. [121]

2004

Case series

Colistin and another agent

In vitro synergy
a

67% of 50 patients with severe Acinetobacter or Pseudomonas infection were cured

or improved

79% of 25 patients with Acinetobacter or

Pseudomonas pneumonia survived until
the end of therapy

NOTE. ICU, intensive care unit; VAP, ventilator-associated pneumonia.

a

Other agents included meropenem, imipenem, aminoglycosides, ampicillin-sulbactam, piperacillin-clavulanate, and ciprofloxacin.

multidrug-resistant Acinetobacter isolates that retain susceptibility. These agents are usually used in conjunction with another
active antimicrobial agent. Many multidrug-resistant Acinetobacter isolates retain intermediate susceptibility to amikacin or
tobramycin; resistance to this class of agents is increasingly
associated with aminoglycoside-modifying enzymes or efflux
pump mechanisms.
Polymyxin therapy. Given limited therapeutic options, clinicians have returned to the use of polymyxin B or polymyxin
E (colistin) for the most drug-resistant Acinetobacter infections
[94, 95]. Colistin acts by disturbing the bacterial cell membrane,
thus increasing permeability, leading to cell death [94]. Colistin
is bactericidal against Acinetobacter species, and its effect is
concentration dependent [95]. Resistance to polymyxins has
been reported, possibly as a result of outer cell membrane
alterations or an efflux pump mechanism [65, 66, 94, 95].
Observational studies have reported rates of cure or improvement for colistin of 57%77% among severely ill patients with
multidrug-resistant Acinetobacter infections, including pneumonia, bacteremia, sepsis, intra-abdominal infection, and CNS
infection [9699]. Although high-quality pharmacokinetic data
are lacking, colistin is reported to have relatively poor lung and
1258 CID 2008:46 (15 April) ANTIMICROBIAL RESISTANCE

CSF distribution, and clinical outcomes vary for different types

of infections [96]. Despite an overall good outcome rate of
67%, Levin et al. [96] found a lower response rate of 25% for
patients with pneumonia due to multidrug-resistant, gram-negative bacilli who were treated with parenteral colistin. Other
studies have reported more favorable clinical response rates
(56%61%) for parenteral colistin treatment of multidrug-resistant Acinetobacter ventilator-associated pneumonia [100
103].
There are case reports of successful treatment of multidrugresistant Acinetobacter meningitis with parenteral colistin, but
its efficacy for this condition remains unclear [104, 105]. Several
case reports and case series report the use of intraventricular
or intrathecal polymyxin therapy, with or without parenteral
therapy, for the treatment of gram-negative bacterial meningitis
[104, 106108]. A recent review of 31 reports involving 64
episodes of gram-negative bacterial meningitis found a cure
rate of 80%, including cure for 10 (91%) of 11 patients with
Acinetobacter meningitis [109]. The majority of patients received systemic antimicrobial therapy in addition to local administration of polymyxin. Neurologic toxicity occurred primarily in reports published before 1970, and the most common

manifestation was meningeal irritation, which was apparently

dose-dependent and reversible [109]. Overall, there is insufficient evidence to draw conclusions regarding the efficacy, safety,
or pharmacokinetic properties of colistin for treatment of CNS
infection, although it remains an important option for salvage
therapy [104].
Data are lacking on the pharmacokinetics, pharmacodynamics, and toxicodynamics of colistin. Earlier methods of measuring serum concentrations of the drug were unable to adequately distinguish concentrations of colistimethate, the
nonactive prodrug, from concentrations of colistin [95]. There
are inconsistencies among manufacturers regarding the recommended dosing of colistin and the units of measurement
employed [95]. Data suggest that current recommended dosing
regimens may lead to serum levels of colistin that are less than
the MIC for Acinetobacter infection [95]. These problems highlight the need for careful pharmacologic studies and the importance of attention to formulation and dosing in clinical care
and research studies.
Synergy and combination therapy. A lack of controlled
clinical trials makes it difficult to evaluate the role of synergy
or combination therapy for multidrug-resistant Acinetobacter
infection. Most available data are from uncontrolled case series,
animal models, or in vitro studies. The studies summarized in
table 2 investigated various combinations of rifampin, sulbactam, aminoglycoside agents, colistin, carbapenems, and other
agents against multidrug-resistant Acinetobacter infection [102,
110123].
Studies have found conflicting results for the same antimicrobial combinations. Montero et al. [113] studied a mouse
model of multidrug-resistant Acinetobacter pneumonia and
found that the combinations of rifampin with imipenem, tobramycin, or colistin were the most effective regimens. A follow-up clinical pilot study, however, cautioned against the use
of rifampin plus imipenem for treatment of carbapenem-resistant Acinetobacter infection, because investigators observed
a high failure rate and documented the emergence of rifampin
resistance in 70% of the patients who were treated with this
regimen [114]. In a guinea pig model, the combination of
imipenem and amikacin was found to be worse than imipenem
alone for treatment of imipenem-resistant pneumonia, despite
the demonstration of in vitro synergy between the agents [116].
The clinical utility of in vitro synergy remains unclear. Most
results for combination therapy are comparable to cure rates
reported for parenteral colistin alone, and the wide variety of
other agents used limits the ability to draw conclusions regarding combination therapy. Controlled clinical studies are
needed to determine whether any antimicrobial combinations
translate into useful therapeutic strategies.
Li et al. [124] found heteroresistance (i.e., subpopulations
with varying levels of resistance to colistin) in 15 of 16 colistin-

susceptible Acinetobacter isolates studied in vitro. Serial passage

of the isolates in the presence of colistin increased the proportion of colistin-resistant subpopulations. Owen et al. [125]
also found in vitro evidence of heteroresistance, suggesting that
combination therapy may be advisable to prevent the emergence of colistin resistance during monotherapy.
CONCLUSIONS
Despite a reputation for relatively low virulence, multidrugresistant Acinetobacter infection poses a formidable threat to
patients. The cause of many outbreaks, this organism is increasingly endemic in the health care setting. Antimicrobial
resistance is increasing, likely as a result both of the emergence
of resistance in the context of antimicrobial pressure and of
health careassociated transmission of drug-resistant strains.
Multidrug-resistant Acinetobacter infections have an extremely
high crude mortality rate and occur most frequently in severely
ill patients. Although the attributable mortality of multidrugresistant Acinetobacter infections is debatable, these infections
are clearly associated with increased time on mechanical ventilation, in the ICU, and in the hospital. Treatment options are
severely limited, and there have been, to our knowledge, no
controlled trials to guide therapeutic choices. Carbapenems and
colistin are the agents of choice for the most drug-resistant
infections. The role of other agents and combination therapy
remains unclear. More data are needed on the pharmacokinetics, pharmacodynamics, and appropriate dosing of colistin,
especially in light of the discovery of heteroresistance. Given
the lack of good therapeutic options, the development of new
therapies, well-controlled clinical trials of existing regimens and
antimicrobial combinations, more research, and greater emphasis on the prevention of health care-associated transmission
of multidrug-resistant Acinetobacter infection are essential.
Acknowledgments
We thank Benedict John Frederick for his assistance developing figure 1.
Financial support. Centers for Disease Control and Prevention (1 K01
CI000300 and 1 R01 CI000530).
Potential conflicts of interest. T.M.P. has been on advisory boards for
Pfizer, Replidyne, and 3M; has received recent research funding from 3M
and Sage; and has received a speaker honorarium from Ortho McNeil.
L.L.M.: no conflicts.

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