The Preantibiotic Era Has Returned

ORIGINAL INVESTIGATION Citywide Clonal Outbreak of Multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY The Preantibiotic Era Has Returned

David Landman, MD; John M. Quale, MD; David Mayorga, MD; Adedeyo Adedeji, MD; Kalyani Vangala, MD; Jayshree Ravishankar, MD; Carlos Flores, MD; Steven Brooks, PhD

Background: Carbapenems are important agents for samples and was isolated from patients at all 15 hospi- treating nosocomial gram-negative infections. Carba- tals. The rate of carbapenem resistance was associated with penem-resistant bacteria have become increasingly prob- cephalosporin use at each hospital (P=.004). For P aeru- lematic in certain regions. This study determined the city- ginosa, 24% were resistant to imipenem, 5% to amika- wide prevalence and molecular epidemiological features cin, and 15% to 29% to other antipseudomonal agents. of carbapenem-resistant Acinetobacter baumannii and Pseu- Ribotyping revealed that 3 clones accounted for nearly domonas aeruginosa in Brooklyn, NY. half of the isolates and were shared by most hospitals.

Methods: All unique patient isolates of A baumannii and Conclusions: Approximately 400 patients were in- P aeruginosa were collected from 15 Brooklyn hospitals fected or colonized with carbapenem-resistant A bau- from July 1, 1999, through September 30, 1999. Antibi- mannii and P aeruginosa during a 3-month period in 1999. otic susceptibilities, the genetic relatedness of resistant A few strains have spread widely throughout hospitals isolates, and the relationship between antibiotic use and in this region. The prevalence of resistant A baumannii resistance rates were determined. seems to be correlated with cephalosporin use. Multire- sistant hospital-acquired bacteria should be viewed as a Results: A total of 419 isolates of A baumannii and 823 serious public health issue rather than an individual hos- isolates of P aeruginosa were collected. For A baumannii, pital’s problem. An intensive coordinated effort will be 53% were resistant to meropenem and/or imipenem, and needed to effectively address this problem. 12% were resistant to all standard antibiotics. Ribotyp- ing revealed that a single clone accounted for 62% of the Arch Intern Med. 2002;162:1515-1520

HE INTRODUCTION of car- These organisms have become endemic to bapenem antibiotics in hospitals in Brooklyn, NY.2 the late 1980s gave clini- Pseudomonas aeruginosa is an estab- cians a powerful tool for lished nosocomial pathogen and a com- the management of nosoco- mon cause of bacteremia in patients in the mialT gram-negative infections. Bacterial re- intensive care unit. While hospital out- sistance to the ureidopenicillins, cepha- breaks of resistant strains have been re- losporins, and fluoroquinolones has been ported, overall imipenem nonsusceptibil- increasing among several gram-negative ity has been approximately 15% of isolates species, such as Pseudomonas aeruginosa, in large North American surveillance stud- Klebsiella pneumoniae, Enterobacter cloa- ies.4,5 Because of the importance of P ae- cae, and Acinetobacter baumannii. Be- ruginosa as a hospital pathogen, increas- cause of this problem, the carbapenems ing carbapenem resistance would be have become increasingly important agents viewed as a serious problem. In this study, From the Department of in many areas. Unfortunately, resistance we assessed the ongoing problem of car- Medicine, State University of to carbapenems has developed among bapenem resistance in Brooklyn by de- New York Downstate Medical these species, particularly A baumannii.1,2 termining the prevalence of antibiotic- Center (Drs Landman, Quale, These organisms are frequently resistant resistant A baumannii and P aeruginosa and Mayorga, Adedeji, Vangala, Ravishankar, and Flores), and to multiple classes of antibiotics, and are the molecular epidemiological features of the Department of often susceptible only to polymyxins. The these organisms at Brooklyn hospitals. Fi- Microbiology, Kingsbrook prevalence of carbapenem-resistant A bau- nally, the association between carba- Jewish Medical Center mannii from 158 hospitals around the penem resistance rates and antibiotic use (Dr Brooks), Brooklyn, NY. United States was 3% from 1994 to 1998.3 at the hospitals was evaluated.

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Downloaded From: https://jamanetwork.com/ on 09/27/2021 MATERIALS AND METHODS lates (minimal inhibitory concentration, Ն16 µg/mL). Typ- ing was also done on a smaller number of carbapenem- susceptible isolates of A baumannii randomly selected from BACTERIAL STRAINS 5 different hospitals. Ribosomal DNA was digested with EcoRI and PvuII for A baumannii and P aeruginosa, respec- The 15 hospitals participating in the study were as fol- tively, according to the manufacturer’s instructions. Pulsed- lows: Beth Israel Medical Center (Kings Highway), Brook- field gel electrophoresis (PFGE) was performed on a se- dale Medical Center, Brooklyn Hospital, Coney Island lect number of carbapenem-resistant isolates of A baumannii Hospital, Department of Veterans Affairs Medical Center selected from different hospitals using SmaI and NotI(New at Brooklyn, Interfaith Medical Center, Kings County England Biolabs, Beverly, Mass), as previously described.2 Hospital, Kingsbrook Medical Center, Long Island Col- The PFGE patterns were interpreted according to the rec- lege Hospital, Lutheran Hospital, Maimonides Medical ommendations of Tenover et al.8 Center, University Hospital, Victory Memorial Hospital, Woodhull Medical Center, and Wyckoff Heights Medical ANTIBIOTIC USE DATA Center. All unique patient isolates of A baumannii and P aeruginosa recovered from routine clinical cultures from Information on antibiotic use during the study period was July 1, 1999, through September 30, 1999, were collected. available from the pharmacies of 12 of the 15 participat- Isolates were identified by the participating microbiology ing hospitals. In most cases, the actual number of units of laboratories using standard techniques. Isolates were each parenteral antibiotic dispensed during the study pe- stored at −70°C in Mueller-Hinton broth with 30% glyc- riod was used. In some cases, only the number of units erol until testing. purchased during the 6-month period from April 1, 1999, through September 30, 1999, was available. Using the SUSCEPTIBILITY TESTING average daily census for each hospital, antibiotic use was expressed as the number of defined daily doses9 of each Minimal inhibitory concentrations were determined for all antibiotic class dispensed (or purchased) per 1000 pa- isolates by the agar-dilution method, as recommended by tient-days. the National Committee for Clinical Laboratory Stan- dards. Ampicillin and sulbactam were tested at a 2:1 ratio, STATISTICAL ANALYSES and the concentration of tazobactam was fixed at 4 µg/ mL. For polymyxin B sulfate, the susceptibility break point The relationship between parenteral antibiotic use and car- was considered to be 4 µg/mL.6 The susceptibility break bapenem resistance rates at each hospital was assessed by points for the other agents were as recommended by the a stepwise multiple linear regression analysis using com- National Committee for Clinical Laboratory Standards. For puter software (Statistical Product and Service Solutions; study purposes, isolates with intermediate susceptibility or SPSS Inc, Chicago, Ill). The following antibiotic classes were resistance were defined as resistant. included in the analysis: aminoglycosides, ␤-lactamase inhibitor combinations, carbapenems, all cephalosporins plus GENETIC STUDIES aztreonam, and fluoroquinolones. The average length of stay and the average daily census for each hospital were also in- Genetic fingerprinting was performed using one system cluded as independent variables. For categorical vari- (RiboPrinter Microbial Characterization System; Quali- ables, ␹2 and Fisher exact tests were used. Statistical sig- con, Wilmington, Del).7 Automated ribotyping was done nificance was defined as PՅ.05. on nearly all meropenem- or imipenem-resistant A bau- This study was approved by the Institutional Review mannii isolates (minimal inhibitory concentration, Ն8 µg/ Board at State University of New York Downstate Medical mL) and on nearly all imipenem-resistant P aeruginosa iso- Center.

RESULTS mediate susceptibility to meropenem were often susceptible to imipenem at the break point (4 µg/mL). Approxi- ACINETOBACTER BAUMANNII mately two thirds of the isolates were susceptible to amikacin and sulbactam, and only about one third were Susceptibility Studies susceptible to ceftazidime and a combination of piperacillin and tazobactam. Among the carbapenem- A total of 419 unique patient isolates of A baumannii were resistant isolates, only half were susceptible to amikacin collected during the 3-month period. The sources of the and sulbactam. Most of these isolates (97%) were sus- isolates were as follows: blood and body fluids, 14%; res- ceptible to polymyxin B sulfate and resistant to the re- piratory, 46%; urine, 19%; wounds, 17%; catheters, 2%; maining antibiotics. Susceptibility did not differ by site and unavailable, 2%. The results of the susceptibility test- of isolation. Five isolates were resistant to all the antibi- ing are shown in Table 1. Overall, more than 50% of otics tested. the isolates were resistant to 1 or both carbapenems and 12% were resistant to all commonly used antibiotics. Car- Genetic Studies bapenem-resistant isolates were found in all 15 hospitals, with resistance rates ranging from 20% to 76% of Ribotype profiles were obtained for 224 carbapenem- all isolates. The activity of imipenem was generally 2-fold resistant isolates of A baumannii (Table 2). A total of 10 greater than that of meropenem, and isolates with inter- unique ribotypes were identified. However, 4 strains (Aci-

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Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 1. Susceptibility Results for Unique Patient Isolates From 15 Brooklyn, NY, Hospitals, July Through September 1999*

Acinetobacter baumannii (n = 419) Pseudomonas aeruginosa (n = 823)

Antibiotic MIC90 Susceptible, % MIC90 Susceptible, % Amikacin 64 69 16 95 Ampicillin/sulbactam 32/16 66 ND ND Cefepime Ͼ64 35 16 76 Ceftazidime Ͼ64 31 32 82 Ceftriaxone sodium Ͼ128 10 ND ND Ciprofloxacin Ͼ827 Ͼ471 Imipenem 16 67 Ͼ16 76 Meropenem 32 47 8 83 Piperacillin/tazobactam Ͼ128/4 33 Ͼ128/4 85 Polymyxin B sulfate 1 98 ND ND

*MIC90 indicates the concentration of antibiotic (in micrograms per milliliter) that is inhibitory to 90% of isolates; ND, not done.

Table 2. Automated Ribotyping Results for 224 A Lane 1 23456789101112 Carbapenem-Resistant Isolates of Acinetobacter baumannii 50 15 Ribotype No. No. (%) of Isolates* No. of Hospitals† 10 1 140 (62) 15 5 2 7 (3) 5 3 43 (19) 8 4 27 (12) 7 5 2 (1) 1 1 61(Ͻ1) 1 B 71(Ͻ1) 1 PFGE Clone A CAAACAABBCB Ͻ 81(1) 1 242 91(Ͻ1) 1 194 10 1 (Ͻ1) 1 145

*Percentages may not total 100 because of rounding. 97 †Those with patients having cultures positive for a given ribotype. 48

netobacter types 1-4) (Table 2) accounted for 97% of the isolates and 1 strain (Acinetobacter type 1) accounted for 62% of all isolates. Isolates from Acinetobacter type 1 were recovered at all 15 Brooklyn hospitals, and isolates from types 2 through 4 were recovered at 5 to 8 of the hospi- C tals. Isolates from Acinetobacter type 1 were less likely to be susceptible to ampicillin or sulbactam than other car- 291 bapenem-resistant isolates (39% vs 71%; PϽ.001). The 5 panresistant isolates included 2 belonging to type 1, 2 be- 242 longing to type 3, and 1 unique strain. Ribotype profiles 145 were also obtained for 48 carbapenem-susceptible isolates 97 randomly selected from 5 of the hospitals. In contrast to 48 the genetic similarity of most carbapenem-resistant isolates, 35 of the 48 susceptible isolates were unique types, Genetic fingerprinting of 12 isolates of carbapenem-resistant Acinetobacter and only 2 were shared by more than a single hospital. baumannii selected from 7 Brooklyn, NY, hospitals. A, Automated ribosomal Pulsed-field gel electrophoresis was performed on DNA digests using Eco RI, revealing 4 distinct ribotypes. B and C, 20 carbapenem-resistant isolates with 4 distinct ribotype Pulsed-field gel electrophoresis (PFGE) of the same isolates using SmaI and profiles. Ribotype profiles and PFGE results of a sample Not I, respectively, revealing 3 unique clones. The numbers along the y-axis indicate values by thousand base pairs. of resistant isolates are shown in the Figure. Pulsed- field gel electrophoresis revealed 3 unique clones. Au- tomated ribotyping and PFGE gave comparable results for 19 of the 20 isolates; a single isolate from PFGE clone 12 of the 15 hospitals. Antibiotics were grouped into C had a unique ribotype. classes as follows: aminoglycosides, fluoroquinolones, ␤-lactamase inhibitor combinations, carbapenems, and Antibiotic Use Data all cephalosporins plus aztreonam (Table 3). In a multivariate analysis, only the use of cephalosporins plus az- Information regarding antibiotic use, average length of treonam was directly associated with the rate of carba- stay, and average daily inpatient census was available at penem-resistant A baumannii and ceftazidime-resistant

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Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 3. Antibiotic Use and Carbapenem-Resistant Acinetobacter baumannii at 12 Brooklyn, NY, Hospitals*

Antibiotic, Daily Dose/1000 Patient-Days

Hospital Average Length ␤-Lactamase Cephalosporins Carbapenem No. of Stay, d Aminoglycosides Fluoroquinolones Inhibitors Carbapenems Plus Aztreonam† Resistance, % 1 8.75 30 25 57 7 69 20 2 6.63 27 31 22 11 66 25 3 6.32 9 37 33 19 145 31 4 NA 55 51 65 6 155 50 5 8.24 35 15 18 7 165 51 6 6.22 52 24 33 12 186 54 7 9.04 42 46 27 3 196 56 8 8.77 36 39 107 13 105 58 9 5.53 NA 20 37 15 136 62 10 5.97 28 47 5 11 218 71 11 6.22 17 20 85 10 173 73 12 5.73 49 32 46 16 228 76

*NA indicates data not available. †P = .004.

Surveillance cultures were performed from envi- Table 4. Automated Ribotyping Results for 136 ronmental surfaces at 10 participating hospitals. Cul- Imipenem-Resistant Isolates of Pseudomonas aeruginosa tures were positive for carbapenem-resistant A baumannii at 7 of the 10 hospitals, particularly involving bed rails Ribotype No. No. (%) of Isolates* No. of Hospitals† and respirator equipment (data not shown). At one hos- 1 26 (19) 12 pital, surveillance cultures were taken from soap dis- 2 20 (15) 10 pensers (containing 2% chlorhexidine gluconate) in 28 3 17 (12) 5 rooms in various patient care areas. Carbapenem- 4 6 (4) 4 5 5 (4) 3 resistant strains of Acinetobacter, Pseudomonas, and K pneu- 6 5 (4) 3 moniae were isolated from 4 of the 28 dispensers. 7 4 (3) 4 8 4 (3) 3 PSEUDOMONAS AERUGINOSA 9 4 (3) 2 10 3 (2) 3 Susceptibility Studies 11 3 (2) 2 12 2 (1) 2 A total of 823 unique patient isolates of P aeruginosa 13 2 (1) 1 14 2 (1) 1 were collected during the 3-month period. The sources 15-47 33 (24) 1 Each of the isolates were as follows: blood and body fluids, 10%; respiratory, 38%; urine, 28%; wounds, 20%; cath- *Percentages may not total 100 because of rounding. eters, 1%; and unavailable, 3%. The results of the sus- †Those with patients having cultures positive for a given ribotype. ceptibility testing are shown in Table 1. Greater than 90% susceptibility was found only for amikacin. Over- A baumannii at each hospital (P =.004 and P =.03, all, only 76% of the isolates were susceptible to imi- respectively). penem. Carbapenem-resistant isolates were recovered at all 15 hospitals, with rates ranging from 12% to 58% Relation Between Cephalosporin of P aeruginosa isolates. Meropenem was approximately and Carbapenem Susceptibility 4-fold more active than imipenem. Six isolates, recovered at 6 different hospitals, were susceptible to none of Ceftriaxone sodium–resistant isolates exhibited re- the tested antibiotics. Among the 196 imipenem-resis- duced susceptibility to the carbapenems, even among tant isolates, the susceptibility rates to amikacin, piper- the carbapenem-susceptible subgroup. For example, acillin-tazobactam, ceftazidime, cefepime, meropenem, among the meropenem-susceptible isolates, ceftriax- and ciprofloxacin were 87%, 61%, 60%, 42%, 31%, and one-resistant isolates were more likely to have a mero- 28%, respectively. Susceptibility did not differ by site of penem minimal inhibitory concentration of 1 µg/mL isolation. than ceftriaxone-susceptible isolates (48% vs 17%; PϽ.001). Ceftriaxone susceptibility also predicted the Genetic Studies molecular characterization of strains. Of the 48 carbapenem-susceptible isolates that were typed, 11 were re- Ribotype profiles were obtained for 136 imipenem- sistant to ceftriaxone. Of these 11, 8 had ribotype pro- resistant isolates of P aeruginosa. The results are shown files belonging to Acinetobacter types 1 to 4, compared in Table 4. A total of 47 unique ribotypes were identi- with only 1 of 37 ceftriaxone-susceptible isolates fied. However, 3 strains (Pseudomonas types 1-3) ac- (PϽ.001). counted for nearly half of all isolates and were recov-

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Downloaded From: https://jamanetwork.com/ on 09/27/2021 ered in 5 to 12 of the participating hospitals. Isolates from to contaminate environmental surfaces and patient care Pseudomonas type 1 were more likely to be susceptible items18 and may spread through the air as well.19,20 In fact, to ceftazidime (81% vs 50%; P=.01) and meropenem (31% surveillance cultures of environmental surfaces were posi- vs 9%; P=.01) and less likely to be susceptible to cipro- tive for carbapenem-resistant A baumannii at most par- floxacin (8% vs 29%; P=.04) than other imipenem- ticipating hospitals. The finding of carbapenem- resistant isolates. Isolates from Pseudomonas type 2 were resistant organisms on soap dispensers at one hospital more likely to be susceptible to ceftazidime (80% vs 52%; suggests that the hands of health personnel may be an P=.04) and piperacillin/tazobactam (100% vs 57%; important vector for nosocomial transmission. Exten- PϽ.001) than other imipenem-resistant isolates. Fi- sive environmental contamination and hand coloniza- nally, isolates from Pseudomonas type 3 were less likely tion are likely to be important factors in the persistence to be susceptible to ceftazidime (24% vs 64%; P=.01) and of this problem. ciprofloxacin (0% vs 29%; P=.02) than other imipenem- Various classes of antibiotics have been associated resistant isolates. with single-hospital outbreaks of resistant Acinetobacter, Among the 73 imipenem-resistant isolates not be- including cephalosporins,21,22 fluoroquinolones,23 amika- longing to types 1 to 3, 44 unique ribotypes were iden- cin,24 and imipenem.1 We found a strong association tified. While 9 of these strains were present in 2 to 5 of between cephalosporin use and rates of carbapenem- the hospitals, most were single unshared isolates. Six iso- resistant A baumannii at hospitals throughout Brooklyn. lates were resistant to all of the tested antibiotics. Ribotype The ribotyping data suggest that most cephalosporin- profiles were obtained for 5 of these 6 isolates, and all 5 resistant A baumannii belong to one of the dominant were unique strains. carbapenem-resistant clones. Therefore, it is under- standable that higher levels of cephalosporin use (Table Antibiotic Use Data 3) might fuel the spread of these organisms. Controlling antibiotic use, particularly cephalosporins, may be an For Pseudomonas, a multivariate analysis revealed no as- important component of strategies to limit the spread of sociation between use of any particular antibiotic class, these pathogens. average length of stay, or average daily inpatient census The emergence of carbapenem-resistant P aerugi- with the carbapenem resistance rates at the hospitals. nosa presents another serious public health problem. The National Nosocomial Infections Surveillance system re- COMMENT ported imipenem resistance rates of 17% for intensive care unit areas, 11% for non–intensive care unit inpatient ar- Carbapenem-resistant A baumannii are becoming a world- eas, and 7% for outpatient areas in US hospitals in 1999.25 wide problem, with outbreaks reported in several Euro- The imipenem resistance rate of 24% for all patient ar- peancountries,10-14 southeastAsia,11,12,15 SouthAmerica,11,12,16 eas in Brooklyn hospitals in this study is substantially Kuwait,12 and the United States.1,2,17 From 1997 to 1998, higher. Unlike A baumannii, which has been an uncom- 2.8% to 5.8% of A baumannii from hospitals across the mon nosocomial pathogen in the past, P aeruginosa is a United States were nonsusceptible to carbapenems.3,4 In well-recognized cause of nosocomial infection. Only ami- most reports, these strains were limited to select hospi- kacin retained reliable activity against the imipenem- tals and tended to be isolated primarily in patients in the resistant P aeruginosa isolates in this study. Of obvious intensive care unit. In 1997, however, carbapenem-resistant concern is the presence of a few isolates that are resis- A baumannii were endemic to most hospitals in Brooklyn.2 tant to all tested antibiotics. In this survey of clinical isolates from 1999, carba- In a previous report,26 increased imipenem use fol- penem resistance rates remained high at all the area hos- lowing an outbreak of extended-spectrum ␤-lactamase– pitals. A retrospective review at several of the hospitals producing K pneumoniae at one hospital resulted in an revealed that more than 35% of A baumannii isolates and increase in imipenem-resistant P aeruginosa. Hospitals in 30% of P aeruginosa isolates represented Centers for Dis- this region are also facing a high prevalence of resistant ease Control and Prevention–defined infection and not K pneumoniae,27 which might cause clinicians to use car- colonization (data not shown). Approximately half of the bapenems more frequently. However, we were unable to patients with A baumannii harbored multiresistant strains, demonstrate any relation between carbapenem use and including 12% that were resistant to all commonly used resistance rates for P aeruginosa. Ribotyping revealed that antibiotics. Only polymyxin B sulfate, a fairly toxic older while multiple strains were detected, 3 comprised the bulk agent, retained activity against nearly all isolates. Ribotyp- of the isolates and were shared by most hospitals. As with ing of these isolates demonstrated that 1 strain ac- A baumannii, nosocomial and interhospital transmis- counted for two thirds of the isolates and was present in sion of these strains is an important part of the ongoing all the hospitals. The PFGE studies demonstrated excel- problem of carbapenem resistance. lent correlation with automated ribotyping. The spread In summary, carbapenem-resistant A baumannii and of the dominant clone among all Brooklyn hospitals may P aeruginosa are common nosocomial pathogens in hos- be due to the sequential hospitalization of colonized pa- pitals throughout Brooklyn. In just a 3-month period, ap- tients at multiple hospitals. The rotation of medical staff proximately 400 patients were colonized or infected with and students among the hospitals may also contribute carbapenem-resistant strains at our hospitals. In 56 of to the spread. Once this multiresistant strain is intro- these cases, the isolate was resistant to all commonly used duced into a hospital’s environment, it seems to be dif- antibiotics. The rate of resistant A baumannii is corre- ficult to eradicate. Acinetobacter species are well-known lated with cephalosporin use at the hospitals. A few strains

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Downloaded From: https://jamanetwork.com/ on 09/27/2021 of each species account for most isolates and are shared 9. Intensive Care Antimicrobial Resistance Epidemiology (ICARE) surveillance re- by most or all hospitals. This problem should be viewed port, data summary from January 1996 through December 1997: a report from the National Nosocomial Infections Surveillance (NNIS) System. Am J Infect Con- as a serious regional public health issue rather than an trol. 1999;27:279-284. individual hospital problem. Only a coordinated strat- 10. Tankovic J, Legrand P, De Gatines G, et al. Characterization of a hospital out- egy of intense surveillance, infection control measures, break of imipenem-resistant Acinetobacter baumannii by phenotypic and geno- and control of inappropriate antibiotic use is likely to ef- typic typing methods. J Clin Microbiol. 1994;32:2677-2681. fectively deal with this problem. 11. Brown S, Bantar C, Young H, Amyes SGB. Limitation of Acinetobacter baumannii treatment by plasmid-mediated carbapenemase ARI-2. Lancet. 1998;351: 186-187. Accepted for publication November 15, 2001. 12. Afzal-Shah M, Livermore DM. Worldwide emergence of carbapenem-resistant This study was supported by AstraZeneca, Wilming- Acinetobacter spp. J Antimicrob Chemother. 1998;41:576-577. ton, Del; Bayer Corp, West Haven, Conn; Dura, San Diego, 13. Riccio ML, Franceschini N, Boschi L, et al. Characterization of the metallo-␤- Calif; Merck, West Point, Pa; Roche, Nutley, NJ; and Wyeth- lactamase determinant of Acinetobacter baumannii AC-54/97 reveals the exist- ence of blaIMP allelic variants carried by gene cassettes of different phylogeny. Ayerst Laboratories, Philadelphia, Pa. Antimicrob Agents Chemother. 2000;44:1229-1235. This study was presented in part at the 40th Annual 14. Bou G, Cervero G, Dominguez MA, Quereda C, Martinez-Beltran J. Characteriza- Interscience Conference on Antimicrobial Agents and Che- tion of a nosocomial outbreak caused by a multiresistant Acinetobacter bauman- motherapy, Toronto, Ontario, September 17-20, 2000; and nii strain with a carbapenem-hydrolyzing enzyme: high level carbapenem resis- ␤ the 38th Infectious Diseases Society of America Annual Meet- tance in A baumannii is not due solely to the presence of -lactamases. J Clin Microbiol. 2000;38:3299-3305. ing, New Orleans, La, September 7-10, 2000. 15. Takahashi A, Yomoda S, Kobayashi I, Okubo T, Tsunoda M, Iyobe S. Detection We thank the members of the microbiology laborato- of carbapenemase-producing Acinetobacter baumannii in a hospital. J Clin Mi- ries of the 15 participating hospitals for their cooperation crobiol. 2000;38:526-529. with this study. 16. Costa SF, Woodcock J, Gill M, et al. Outer-membrane proteins pattern and de- ␤ Corresponding author and reprints: John M. 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