Increasing Resistance of Acinetobacter Species to Imipenem in United States Hospitals,1999–2006 • Author(s): Marc S. Hoffmann, MD; Michael R. Eber, BSE; Ramanan Laxminarayan, PhD, MPHSource: Infection Control and Hospital Epidemiology, Vol. 31, No. 2 (February 2010), pp. 196-197Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/10.1086/650379 .

Accessed: 18/05/2014 02:32

Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at .http://www.jstor.org/page/info/about/policies/terms.jsp

.JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range ofcontent in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new formsof scholarship. For more information about JSTOR, please contact support@jstor.org.

.

The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaboratingwith JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology.

http://www.jstor.org

This content downloaded from 91.229.248.50 on Sun, 18 May 2014 02:32:02 AMAll use subject to JSTOR Terms and Conditions

196 infection control and hospital epidemiology february 2010, vol. 31, no. 2

table. Percentages of Acinetobacter Isolates Resistant or Susceptible to Imipenem, United States Hospitals, 1999–2006

Response to imipenem1999

(n p 3,829)2000

(n p 5,636)2001

(n p 5,851)2002

(n p 6,293)2003

(n p 5,928)2004

(n p 7,246)2005

(n p 6,778)2006

(n p 5,854)

Resistance 4.5 6.4 7.7 6.8 9.6 12.6 18.4 18.2Intermediate resistance 1.3 5.0 5.8 6.5 4.3 4.2 7.1 9.4Susceptibility 94.1 88.6 86.4 86.7 86.1 83.1 74.5 72.4

note. Percentages may not add to 100 because of rounding.

references

1. Alazmi W, Bustamante M, O’Loughlin C, Gonzalez J, Raskin JB. Theassociation of Streptococcus bovis bacteremia and gastrointestinal diseases:a retrospective analysis. Dig Dis Sci 2006;51:732–736.

2. Lee RA, Woo PC, To AP, Lau SK, Wong SS, Yuen KY. Geographical dif-ference of disease association in Streptococcus gallolyticus bacteraemia. JMed Microbiol 2003;52:903–908.

3. Gerber JS, Glas M, Frank G, Shah SS. Streptococcus gallolyticus infectionin young infants. Pediatr Infect Dis J 2006;25:1069–1073.

4. Gavin PJ, Thomson RB Jr, Horng SJ, Yogev R. Neonatal sepsis causedby Streptococcus gallolyticus variant (biotype II/2): report of a case andreview. J Clin Microbiol 2003;41:3433–3435.

5. Poyart C, Quesne G, Trieu-Cuot P. Taxonomic dissection of the Strep-tococcus gallolyticus group by analysis of manganese-dependent super-oxide dismutase gene (sodA) sequences: reclassification of ‘Streptococcusinfantarius subsp. coli’ as Streptococcus lutetiensis sp. nov. and of Strep-tococcus gallolyticus biotype II.2 as Streptococcus pasteurianus sp. nov. IntJ Syst Evol Microbiol 2002;52:1247–1255.

6. Talon D, Mulin B, Dupont MJ, Chareton AM, Thouverez M. Epide-miology of penicillin resistance in Streptococcus pneumoniae isolates ineastern France. Clin Microbiol Infect 1998;4:11–17.

7. Tenover FC, Arbeit RD, Goering RV, et al. Interpreting chromosomalDNA restriction patterns produced by pulsed-field gel electrophoresis:criteria for bacterial strain typing. J Clin Microbiol 1995;33:2233–2239.

8. Srivastava S, Shetty N. Healthcare-associated infections in neonatal units:lessons from contrasting worlds. J Hosp Infect 2007;65:292–306.

9. Chadfield MS, Christensen JP, Decostere A, Christensen H, Bisgaard M.Geno- and phenotypic diversity of avian isolates of Streptococcus gal-lolyticus subsp. gallolyticus (Streptococcus gallolyticus) and associated di-agnostic problems. J Clin Microbiol 2007;45:822–827.

10. Boyce JM. Environmental contamination makes an important contri-bution to hospital infection. J Hosp Infect 2007;65(suppl 2):50–54.

Increasing Resistance of AcinetobacterSpecies to Imipenem in United StatesHospitals, 1999–2006

Acinetobacter is an increasingly important hospital-associatedpathogen.1 Multidrug resistance among Acinetobacter speciescontinues to rise,2 and infection with these multidrug-resis-tant organisms has a profound negative impact on patientoutcomes.3 Carbapenem resistance is frequently used by hos-pitals as a definition for multidrug resistance among Acine-tobacter species, because it is often associated with resistanceto other antibiotic classes.3 Increasing carbapenem resistanceamong Acinetobacter species in United States hospitals has

been documented in recent studies by the Centers for DiseaseControl and Prevention.4,5 However, these reports were lim-ited by the number of Acinetobacter isolates examined andwere not based on nationally representative samples of UShospitals. Using the largest sample size to date (to our knowl-edge), we examined US national and regional trends in ratesof imipenem resistance among clinical isolates of Acineto-bacter species collected from hospital inpatients.

We used susceptibility results from The Surveillance Net-work Database—USA (TSN), a nationally and regionally rep-resentative database of bacterial susceptibility records gath-ered from 300 US hospitals. The database is described in detailelsewhere.6,7 Participating laboratories are required to submitall bacterial isolates for which species identification and an-tibiotic sensitivities are recorded. Only laboratories that arecertified by the Clinical Laboratory Standards Institute (CLSI)and that report on the basis of CLSI reference methods areincluded.

Our analysis considered inpatient isolates reported overthe period 1999–2006 that were identified as Acinetobacterspecies and tested for susceptibility to imipenem. Data werefiltered to retain only the first isolate from a patient in a givenyear, regardless of specimen source or susceptibility, to avoidbias from duplicate isolates.8 The x2 test for linear trend wasused to test the significance of yearly trends in susceptibilitylevels. Statistical significance was set at the .05 level. All sta-tistical analysis was conducted using Stata, version 10.0(StataCorp).

Data on a total of 47,415 Acinetobacter isolates testedagainst imipenem were collected over the period 1999–2006.Isolates recovered from patients in intensive care units (ICUs)accounted for 15,726 (33%) of all isolates. The most commonsources of isolates were the respiratory tract (51.6%), urine(13.6%), wounds (21.5%), and blood (12.4%). Isolates orig-inated from the following US Census regional divisions: EastNorth Central (13.3%), East South Central (5.3%), MiddleAtlantic (20.7%), Mountain (6.7%), New England (2.1%),Pacific (15.9%), South Atlantic (22.4%), West North Central(5.3%), and West South Central (8.4%).

The proportions of inpatient isolates tested against imi-penem that were resistant, intermediately resistant, and sus-ceptible to this agent during each year over the period 1999–2006 are shown in the Table. Imipenem-susceptible isolatesdecreased as a share of all tested isolates by more than anabsolute 20% over the study period, from 94.1% in 1999 to72.4% in 2006 ( ).P ! .001

This content downloaded from 91.229.248.50 on Sun, 18 May 2014 02:32:02 AMAll use subject to JSTOR Terms and Conditions

research briefs 197

The Middle Atlantic region was the only US area to exhibitimipenem susceptibility of less than 90% in either 1999 or2000 (82% susceptibility in the Middle Atlantic region in 1999and 71% in 2000). However, imipenem susceptibility de-creased in 8 of 9 US regions ( for each region), andP ! .05by 2006, these 8 regions each exhibited imipenem suscepti-bility of less than 85%. The East South Central region wasthe only region that did not exhibit a significant decrease inimipenem susceptibility among Acinetobacter isolates (P p

for the trend); it showed 96.5% susceptibility in 2006..675By use of the largest sample size to date (to our knowledge),

our results demonstrate substantial national and regional in-creases in carbapenem resistance among clinical isolates ofAcinetobacter species over the period 1999–2006. Increasingcarbapenem resistance among Acinetobacter species is partic-ularly troubling, because it is very often associated with mul-tidrug resistance3 and because it is occurring in the contextof increases in the incidence of Acinetobacter infection.1

Although the national imipenem resistance rate in oursample is high at about 18% in 2006, it is substantially lowerthan recent estimates by Hidron et al,4 who documented im-ipenem resistance rates from 26% to 37% among pathogenicAcinetobacter baumannii isolates. These estimates by Hidronet al4 may be higher for the following reasons: first, fewerthan 500 isolates per year were used for analysis; second,carbapenem resistance was defined as either imipenem resis-tance or meropenem resistance; third, only isolates from pa-tients with healthcare-associated infection were considered;and fourth, the sample of hospitals used for analysis was notnationally representative. Our estimates are lower than thoseof Carey et al5 as well, who documented a 40% carbapenemresistance rate in 2004 among ICU patients. However, ourresults suggest a much higher national level of imipenemresistance than a study by Lockhart et al9 that found only a5% resistance rate among Acinetobacter isolates recoveredfrom ICU patients during the period 2002–2004.

Our study has some limitations. First, the TSN database isdesigned to be representative of US hospitals, but it may notcapture the entire distribution of resistance rates in US hos-pitals. Nevertheless, our results are not likely to be biased bylocalized epidemics, because of the large sample size of theTSN database. Second, TSN reports only the site of the isolate,and clinical data are not available to confirm infection. Third,we note that test selection procedure may influence our re-sults; as resistance to an antibiotic becomes established, iso-lates may be tested for susceptibility to the antibiotic morefrequently. Fourth, we do not know whether potential in-accuracies among accepted laboratory testing methods mightbias our results.10

In summary, this study confirmed substantial increases inthe frequency of imipenem resistance among clinical Acine-tobacter isolates in recent years. Resistant Acinetobacter speciesshould be a high priority for disease control.

acknowledgments

Financial support. The Pioneer Portfolio of the Robert Wood JohnsonFoundation (grant 61119 to R.L. and M.R.E.).

Potential conflicts of interest. All authors report no conflicts of interestrelevant to this article.

Marc S. Hoffmann, MD; Michael R. Eber, BSE;Ramanan Laxminarayan, PhD, MPH

From the University of Pennsylvania School of Medicine, Philadelphia,Pennsylvania (M.S.H.); Center for Disease Dynamics, Economics & Policy,Resources for the Future, Washington, DC (M.R.E., R.L.); and PrincetonEnvironmental Institute, Princeton University, Princeton, New Jersey (R.L.).M.S.H. and M.R.E. share joint first authorship.

Address reprint requests to Ramanan Laxminarayan, PhD, MPH,Resources for the Future, 1616 P St NW, Ste 632, Washington, DC 20036(ramanan@rff.org).

Received July 17, 2009; accepted August 9, 2009; electronically publishedDecember 23, 2009.� 2009 by The Society for Healthcare Epidemiology of America. All rightsreserved. 0899-823X/2010/3102-0017$15.00. DOI: 10.1086/650379

references

1. Gaynes R, Edwards JR. Overview of nosocomial infections caused bygram-negative bacilli. Clin Infect Dis 2005;41:848–854.

2. Munoz-Price LS, Weinstein RA. Acinetobacter infection. N Engl J Med2008;358:1271–1281.

3. Maragakis LL, Perl TM. Acinetobacter baumannii: epidemiology, anti-microbial resistance, and treatment options. Clin Infect Dis 2008;46:1254–1263.

4. Hidron AI, Edwards JR, Patel J, et al. NHSN annual update: antimicro-bial-resistant pathogens associated with healthcare-associated infections:annual summary of data reported to the National Healthcare SafetyNetwork at the Centers for Disease Control and Prevention, 2006–2007.Infect Control Hosp Epidemiol 2008;29:996–1011.

5. Carey RB, Banerjee S, Srinivasan A. Multidrug-resistant Acinetobacterinfections, 1995–2004. In: Program and abstracts of the 46th InterscienceConference on Antimicrobial Agents and Chemotherapy; September 27–30, 2006; San Francisco, CA.

6. Styers D, Sheehan DJ, Hogan P, Sahm DF. Laboratory-based surveillanceof current antimicrobial resistance patterns and trends among Staphy-lococcus aureus: 2005 status in the United States. Ann Clin MicrobiolAntimicrob 2006;5:2.

7. Sahm DF, Marsilio MK, Piazza G. Antimicrobial resistance in key blood-stream bacterial isolates: electronic surveillance with The SurveillanceNetwork Database—USA. Clin Infect Dis 1999;29:259–263.

8. Hindler JF, Stelling J. Analysis and presentation of cumulative antibio-grams: a new consensus guideline from the Clinical and LaboratoryStandards Institute. Clin Infect Dis 2007;44:867–873.

9. Lockhart SR, Abramson MA, Beekmann SE, et al. Antimicrobial resis-tance among gram-negative bacilli causing infections in intensive careunit patients in the United States between 1993 and 2004. J Clin Microbiol2007;45:3352–3359.

10. Kulah C, Aktas E, Comert F, Ozlu N, Akyar I, Ankarali H. Detectingimipenem resistance in Acinetobacter baumannii by automated systems(BD Phoenix, Microscan WalkAway, Vitek 2); high error rates with Mi-croscan WalkAway. BMC Infect Dis 2009;9:30.

This content downloaded from 91.229.248.50 on Sun, 18 May 2014 02:32:02 AMAll use subject to JSTOR Terms and Conditions