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Letter
Polymyxin-Resistant Acinetobacter
spp. Isolates: What Is Next?
Adriana O. Reis,* Deise A.M. Luz,* Maria C.B. Tognim,* Hélio S. Sader,*
and Ana C. Gales*
*Universidade Federal de São Paulo, São Paulo, Brazil
Suggested citation for this article: Reis AO,
Luz DAM, Tognim MCB, Sader HS, and Gales AC. Polymyxin-resistant Acinetobacter
spp. isolates: what is next?. Emerg Infect Dis [serial online] 2003
Aug [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no8/03-0052.htm
To the Editor: In Brazilian hospitals, Acinetobacter spp.
has been an important etiologic agent of nosocomial infections, mainly
pneumonia (1–3). In general, ampicillin/sulbactam and
carbapenems remain the last therapeutic options for treatment of such
infections (3,4). However, resistance rates to carbapenems
have increased, reaching rates approximately 12% or higher in some Brazilian
hospitals (1,3,4). Thus, more toxic agents such as polymyxins
have been used as alternative therapeutic drugs against multidrug-resistant
Acinetobacter infections (5,6). The clinical use
of polymyxins has been based on antimicrobial susceptibility results and
previous clinical experience. However, the National Committee for Clinical
Laboratory Standards (NCCLS) documents do not currently provide interpretative
criteria for the testing of polymyxins (7). In addition,
the disk diffusion technique was reported to be an unreliable method for
evaluating the susceptibility to polymyxins (8). Since
Acinetobacter clinical specimens exhibiting high MICs for polymyxins
(MIC, 8–32 mg/mL) were recently detected, we searched for the frequency
of occurrence of Acinetobacter spp. strains exhibiting reduced
susceptibility to polymyxin B among 100 bloodstream isolates of Acinetobacter
spp. (8). The bacterial isolates were consecutively collected
between September 1999 and December 2000 from a tertiary Brazilian hospital,
where Acinetobacter spp. infections have reached endemic levels
and polymyxins have been frequently used. Only one isolate per patient
was included in the study.
The isolates were identified to the species level using the BBL Crystal
System (Becton Dickinson, Sparks, MD). The susceptibility to polymyxin
B and meropenem were tested by disk diffusion and agar dilution techniques
according to NCCLS recommendations (9,10). The susceptibility
interpretative criteria for meropenem and polymyxin B were based on the
current and former NCCLS documents, respectively (7,11).
The MIC was defined as the lowest antimicrobial concentration that inhibited
bacterial growth. Pseudomonas aeruginosa ATCC 27853, Staphylococcus
aureus ATCC 25923, and Escherichia coli ATCC 25922 were used
as quality control strains. Testing errors and agreements were determined
by comparing the results of the disk diffusion with the standard criterion
agar dilution method. Categorical agreement was obtained when the isolates
were classified within the same susceptibility category. The very major
and major errors were related to false susceptibility and false resistance
results, respectively. To evaluate whether the polymyxin B-resistant strains
isolates were epidemiologically related, these isolates were molecularly
typed by pulsed-field gel electrophoresis (PFGE) as previously described
(12). PFGE patterns were considered identical if they
shared every band, similar if they differed from one to three bands, and
distinct if they differed by four or more bands (12).
Despite the limitation of commercial systems for identifying the genus
Acinetobacter at species level, Acinetobacter baumannii
(80.0%) was the most commonly identified species, followed by A. lwoffi
(4.0%). Sixteen percent of the Acinetobacter isolates were not
identified to species level by the BBL Crystal System. Meropenem (MIC50,
1 mg/mL) and polymyxin B (MIC50, 1 mg/mL) showed similar in vitro potency.
However, meropenem exhibited the highest susceptibility rate (99.0% susceptible).
In contrast to previous studies, only one strain was resistant to meropenem
(1,2,3,8), which indicates that the carbapenem-susceptibility
rates among Acinetobacter spp. isolates may vary according to the
period evaluated even in the same institution. By using the polymyxin
B resistance breakpoint (MIC >4 mg/mL) presented by the former
NCCLS document, which was recently validated, we found that five Acinetobacter
spp. isolates were considered resistant to polymyxin B (MICs, 8–32 mg/mL)
(8,11). All isolates were susceptible
to meropenem and belonged to A. baumannnii (4)
and A. lwoffi (1) species. The polymyxin B–resistant
isolates were categorized as susceptible by disk diffusion (100%, very
major error). The disk diffusion method is widely used in Brazil and worldwide.
However, disk diffusion was confirmed to be an unreliable test for detecting
Acinetobacter spp. isolates with reduced susceptibility to polymyxins.
These results are in agreement with those previously reported (8).
Among the five polymyxin B–resistant Acinetobacter spp., four
distinct patterns were characterized by PFGE. Two polymyxin B–resistant
strains, which were isolated from different units of the São Paulo Hospital
complex, shared an identical PFGE pattern. The PFGE results suggest that
the polymyxin B use may have played a role in the selection of resistant
strains. On the other hand, two isolates shared an identical PFGE pattern,
which raises the possibility of patient-to-patient transmission of epidemic
strains. Intra- and interhospital dissemination of multidrug-resistant
Acinetobacter spp. clones has already been reported in Brazilian
hospitals (13).
Our findings suggest that the polymyxin B–resistant strains have emerged
because of antimicrobial selective pressure and dissemination of clonal
strains. Further epidemiologic studies are necessary to correlate the
emergence of polymyxin-resistant Acinetobacter spp. isolates to
the clinical response with polymyxin B therapy. Since the emergence of
polymyxin B resistance may leave no efficacious drugs for the treatment
of infections caused by multidrug-resistant Acinetobacter spp.
isolates, strict infection control measures must be adopted to avoid the
emergence and spread of such isolates. The low accuracy of routine susceptibility
tests, especially disk diffusion, may jeopardize rapid implementation
of such measures.
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