- Email: [email protected]
Nosocomial spread of Pseudomonas aeruginosa producing the metallo-β-lactamase VIM-2 in a Spanish hospital: clinical and epidemiological implications
1026 Clinical Microbiology and Infection, Volume 13 Number 10, October 2007
RESEARCH NOTE Nosocomial spread of Pseudomonas aeruginosa producing the metallo-blactamase VIM-2 in a Spanish hospital: clinical and epidemiological implications C. Pen˜a1, C. Suarez1, F. Tubau2, O. Gutierrez3, A. Domı´nguez2, A. Oliver3, M. Pujol1, F. Gudiol1 and J. Ariza1 1
Infectious Diseases Service, 2Microbiology Service, IDIBELL, Hospital Universitari de Bellvitge, Barcelona and 3Microbiology Service, Hospital de Son Doreta, Palma de Mallorca, Spain
ABSTRACT Thirty-four isolates of pan-resistant Pseudomonas aeruginosa producing VIM-2 metallo-b-lactamase (MBL) were detected at a university hospital in Spain (July 2004-September 2006). Eleven (32%) patients had clinically significant infections, and three (27%) of these patients died. A single clone of MBL-producing P. aeruginosa was identified by pulsed-field gel electrophoresis. A cluster of isolates associated with the vascular surgery ward involved ten patients and appeared as a series of low-grade, sustained and misdiagnosed endemic infections in the hospital. The identification of MBL-positive P. aeruginosa should be considered mandatory in the surveillance of pan-resistant P. aeruginosa and requires a high index of suspicion in the context of endemic infections with a low attack rate. Keywords Epidemiology, metallo-b-lactamase, panresistance, Pseudomonas aeruginosa, surveillance, VIM-2 Original Submission: 16 February 2007; Revised Submission: 24 April 2007; Accepted: 2 May 2007
Clin Microbiol Infect 2007; 13: 1026–1029 10.1111/j.1469-0691.2007.01784.x
Corresponding author and reprint requests: C. Pen˜a, Infectious Diseases Service, Hospital Universitari de Bellvitge, C ⁄ Feixa Llarga s ⁄ n 08907, L’Hospitalet de Llobregat, Barcelona, Spain E-mail: [email protected]
Resistance to b-lactams, including carbapenems, in Pseudomonas aeruginosa may result from the acquisition of various b-lactamases, including metallo-b-lactamases (MBLs) [1,2]. Although MBLs were first detected in Spain in 2002 [3], very few MBL-producing P. aeruginosa (MBL-PA) strains have been found in Spain (0.08% of P. aeruginosa isolates in a recent multicentre study) (unpublished results). In the Hospital Universitari de Bellvitge (Barcelona, Spain), which is a 900-bed public institution, a cluster of pan-resistant P. aeruginosa (PR-PA) isolates producing MBLs was suspected in the vascular surgery ward in May 2005. PR-PA isolates were defined as being resistant to all b-lactam and fluoroquinolone antibiotics [4]. The phenotype of these PR-PA isolates, showing high-level resistance to all b-lactams with the exception of aztreonam, suggested the production of a carbapenem-hydrolysing MBL. From May 2005 onwards, prospective ward-based and laboratory-based surveillance was used to identify new cases of PR-PA, and clinical samples were further investigated to identify MBL producers. In addition, all PR-PA isolates from July 2004 were screened retrospectively for MBL production, and the charts of the patients with P. aeruginosa isolates that carried a transferable MBL gene (see below) were reviewed retrospectively. P. aeruginosa was identified by standard methods. MICs were initially determined using the MicroScan automated microdilution system (Dade International, West Sacramento, CA, USA) and Etests (AB Biodisk, Solna, Sweden). CLSI criteria [5] were used to define resistance. The double-disk synergy test (DDST), with ceftazidime (30 lg), imipenem (10 lg) and EDTA disks (1900 lg), was used to screen isolates for MBLs [6], and the synergy MBL Etest [7] was used to further assess MBL production. Genes encoding IMP and VIM MBLs were detected by PCR in all DDST-positive isolates, using the universal blaIMP and blaVIM primers IMP-UP, IMP-DN, VIM-B and VIM-F, respectively [8,9]. To characterise the MBL, a PCR specific for blaVIM-2 (the most prevalent MBL in southern Europe) and related genes was performed with two representative isolates. Primers VIM-2F and VIM-2R [10] were used to amplify the complete coding sequence of blaVIM-2, which was then fully sequenced for both isolates. Typing, using pulsed-field gel electrophoresis of genomic DNA digested by SpeI, was
2007 The Authors Journal Compilation 2007 European Society of Clinical Microbiology and Infectious Diseases, CMI, 13, 1023–1035
Research Notes 1027
performed for 20 blaVIM-positive P. aeruginosa isolates, representative of the entire period, with the results being interpreted as described previously [11]. Between July 2004 and September 2006, 2363 patients with P. aeruginosa-positive clinical samples were detected, with 677 (29%) yielding carbapenem-resistant isolates, of which 34 (5%) were MBL-producing isolates. Following the index case, which occurred in May 2005 in the vascular surgery ward, nine additional cases were detected prospectively. Prospective surveillance during the next 12 months revealed successful control of MBL-PA clustering in the vascular ward after reinforcement of the use of barrier precautions. Among 34 cases detected (Fig. 1), 23 (68%) were males (mean age 62 years). All isolates except one were nosocomial; the community-acquired MBL-PA isolate was from a female aged 71 years, with a chronic lung disease. The mean length of stay before isolation of MBL-PA
Vascular
ICU
was 35.6 days. Eleven (32%) patients were infected and 23 (68%) were colonised. Of the 11 infected patients, two received antibiotic therapy alone; evaluation of the efficacy of the antimicrobial therapy in the remaining nine cases was complicated by concomitant surgical drainage (Table 1). The overall mortality rate was 27%, and only one death was related to the infection as a result of multi-organ failure secondary to respiratory tract infection. The 34 isolates were highly resistant to imipenem (MIC >256 mg ⁄ L) and meropenem (MIC >32 mg ⁄ L). All isolates also demonstrated resistance to all cephalosporins, penicillins, aminoglycosides and fluoroquinolones, but were uniformly susceptible to colistin. MICs of aztreonam were lower, although ten isolates showed resistance (MIC >8 mg ⁄ L). All isolates selected, one for each patient, showed a synergic inhibition zone with the DDST, and a decrease in imipenem MIC was observed in the presence of EDTA with
Orthopaedic
Urology
Healthcare
No. of patients colonised/infected by MBL-PA
4
3
2
1
Ju A ly Se ugu 04 pt s em t 0 4 b O c er No tob 04 ve er De mb 04 ce er m 04 Ja ber n 0 Fe uar 4 br y 0 eu 5 M ry 0 ar ch 5 Ap 05 ril 0 M 5 ay Ju 05 ne Ju 05 A ly Se ug 05 pt us em t 0 O be 5 c r No tob 05 ve er De mb 05 ce er m 05 Ja ber nu 0 Fe ar 5 br y 0 eu 6 M ry 0 ar ch 6 Ap 06 ril M 06 ay Ju 06 ne Ju 06 A ly Se ug 06 pt us em t 0 be 6 r0 6
0
Cluster Retrospective study Prospective study Fig. 1. Number of patients colonised or infected with metallo-b-lactamase producing Pseudomonas aeruginosa (MBL-PA). ICU, intensive care unit. 2007 The Authors Journal Compilation 2007 European Society of Clinical Microbiology and Infectious Diseases, CMI, 13, 1023–1035
1028 Clinical Microbiology and Infection, Volume 13 Number 10, October 2007
Table 1. Clinical characteristics and outcome of 11 patients with infections caused by Pseudomonas aeruginosa isolates producing metallo-b-lactamase Patient
Date
Diagnosis at admission
Duration (days) of previous antibiotic treatment
1
July 2004
Vascular illness
CIP (20) AMC (5)
2
August 2004
Liver transplantation
ATM (5)
3
September 2004
None
4
October 2004
5
March 2005
Vascular illness Joint illness Liver transplantation Vascular illness Vascular illness Chronic renal failure Vascular illness Vascular illness Multiple trauma
6
April 2005
7
June 2005
8
June 2005
9
September 2005
10
November 2005
11
September 2006
Oesophageal perforation
CIP (11) ATM (6) MEM (7) AMC (10)
Source Vascular prosthesis, blood Catheter vascular blood Surgical wound Prosthesis, knee BAL fluid specimen Bone
Empirical antibiotic treatment
Non-antibiotic treatment
Definitive antibiotic treatment
Outcome
None
Removal of prosthesis + amputation Removal of catheter
None
Discharged
None
Death (30 days)
CIP
Amputation
None
Discharged
None
Surgical drainage –
ATM
Relapse
–
Finger amputation Amputation
None TZP
Death (1 day) Death (45 days) Discharged
Non-surgical drainage –
TZP
Discharged
ATM
Discharged
Removal of urinary catheter Surgical drainage
TZP
Discharged
AMK ATM
Discharged
TZP + AMK
MEM + AMK None
CIP (15)
Surgical wound
IMP
TZP (12)
Bone
None
CIP (23)
Bone
None
CAZ(15) IMP (14)
Urine
TZP
TZP (23) MEM (8) IMP (12)
Intra-abdominal abscess
IMP
CIP, ciprofloxacin; AMC, amoxycillin–clavulanic acid; ATM, aztreonam; MEM, meropenem; TZP, piperacillin–tazobactam; CAZ, ceftazidime; IMP, imipenem; AMK, amikacin.
the MBL Etest. Positive PCR results were obtained with the VIM primers, and sequencing confirmed the presence of blaVIM-2. An identical pulsed-field gel electrophoresis profile was found for all 20 isolates tested, including the community-acquired MBL-PA isolate. The observation of a cluster of cases involving MBL-PA isolates among vascular surgery patients revealed the presence of a low-level, insidious and sustained monoclonal endemic of MBL-PA isolates throughout the various wards of the hospital, including the intensive care units, over a relatively long period. To date, P. aeruginosa isolates with acquired MBL determinants have usually occurred sporadically or have caused small nosocomial outbreaks [8,10,12], while longitudinal surveys have demonstrated a variable level of endemicity of MBL producers [13]. VIM-2 was first identified in P. aeruginosa isolates in southern France [10], and is the most frequently acquired MBL worldwide. Similar VIM-producing P. aeruginosa strains have been described in other areas of Europe in recent years [3,14–18]. However, to our knowledge, this study is the first report of a cluster of infections caused by MBL-producing P. aeruginosa in Spain. The
similarity of the pan-resistant phenotype to that found in many non-MBL-PA isolates in the same hospital complicates the detection of MBL-producing isolates; it was not until the emergence of a cluster of cases in the vascular surgery ward that it was apparent that there was an insidious sustained monoclonal endemic occurring in the hospital. The clinical consequences of the endemic were probably only moderate, as has been suggested previously [19,20], based on the low (30%) prevalence of infected patients and an overall mortality rate of <30% in a population with severe co-morbid illness. However, the multiresistant MBL-PA isolates create important therapeutic problems and are associated with high rates of morbidity. In conclusion, the identification and surveillance of MBL-PA isolates should not be considered trivial. The difficulty of their identification in an outbreak setting, or in an endemic setting with a low attack rate, requires a high index of suspicion and the systematic inclusion of DDST and genotyping studies in nosocomial surveillance programmes for multiresistant P. aeruginosa.
2007 The Authors Journal Compilation 2007 European Society of Clinical Microbiology and Infectious Diseases, CMI, 13, 1023–1035
Research Notes 1029
ACKNOWLEDGEMENTS This work was supported by National Health Service grant FIS 03 ⁄ 0029 from the Fondo de Investigacio´n Sanitarias and also by the Ministerio de Sanidad y Consumo, the Instituto de Salud Carlos III, and the Spanish Network for the Research in Infectious Diseases (grants REIPI C03 ⁄ 14 and REIPI RD06 ⁄ 0008).
11.
12.
REFERENCES 1. Watanabe M, Iyobe S, Inoue M, Mitsuhashi S. Transferable imipenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1991; 35: 147–151. 2. Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect 2002; 8: 321–331. 3. Prats G, Miro I, Mirelis B, Poirel L, Bellais S, Nordmann P. First isolation of a carbapenem-hydrolyzing b-lactamase in Pseudomonas aeruginosa in Spain. Antimicrob Agents Chemother 2002; 46: 932–933. 4. Paterson DL. The epidemiological profile of infections with multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species. Clin Infect Dis 2006; 43 (suppl 2): S43–S48. 5. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, 16th informational supplement, document M100-S16. Wayne, PA: CLSI, 2006. 6. Lee K, Sim YS, Yong D et al. Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-b-lactamase-producing isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol 2003; 41: 4623–4629. 7. Walsh TR, Bolmstrom A, Qwarnstrom A, Gales A. Evaluation of a new Etest for detecting metallo-b-lactamases in routine clinical testing. J Clin Microbiol 2002; 40: 2755–2759. 8. Senda K, Arakawa Y, Nakashima K et al. Multifocal outbreaks of metallo-b-lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum b-lactams, including carbapenems. Antimicrob Agents Chemother 1996; 40: 349–353. 9. Lauretti L, Riccio ML, Mazzariol A et al. Cloning and characterization of blaVIM, a new integron-borne metallob-lactamase gene from a Pseudomonas aeruginosa clinical isolate. Antimicrob Agents Chemother 1999; 43: 1584–1590. 10. Poirel L, Naas T, Nicolas D et al. Characterization of VIM2, a carbapenem-hydrolyzing metallo-b-lactamase and its
13.
14.
15.
16.
17.
18.
19.
20.
plasmid- and integron-borne gene from a Pseudomonas aeruginosa clinical isolate in France. Antimicrob Agents Chemother 2000; 44: 891–897. Tenover FC, Arbeit RD, Goering RV et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995; 33: 2233–2239. Cornaglia G, Mazzariol A, Lauretti L, Rossolini GM, Fontana R. Hospital outbreak of carbapenem-resistant Pseudomonas aeruginosa producing VIM-1, a novel transferable metallo-b-lactamase. Clin Infect Dis 2000; 31: 1119–1125. Rossolini GM, Riccio ML, Cornaglia G et al. Carbapenemresistant Pseudomonas aeruginosa with acquired blaVIM metallo-b-lactamase determinants, Italy. Emerg Infect Dis 2000; 6: 312–313. Cardoso O, Leitao R, Figuereido A, Sousa JC, Duarte A, Peixe L. Metallo-beta-lactamase VIM-2 in clinical isolates of Pseudomonas aeruginosa from Portugal. Microb Drug Resist 2002; 8: 93–97. Pournaras S, Maniati M, Petinaki E et al. Hospital outbreak of multiple clones of Pseudomonas aeruginosa carrying the unrelated metallo-beta-lactamase gene variants blaVIM-2 and blaVIM-4. J Antimicrob Chemother 2003; 51: 1409–1414. Aubron C, Poirel L, Fortineau N, Nicolas P, Collet L, Nordmann P. Nosocomial spread of Pseudomonas aeruginosa isolates expressing the metallo-b-lactamase VIM-2 in a hematology unit of a French hospital. Microb Drug Resist 2005; 11: 254–259. Henrichfreise B, Wiegand I, Sherwood KJ, Wiedemann B. Detection of VIM-2 metallo-b-lactamase in Pseudomonas aeruginosa from Germany. Antimicrob Agents Chemother 2005; 49: 1668–1669. Deplano A, Rodriguez-Villalobos H, Glupczynski Y et al. Emergence and dissemination of multidrug resistant clones of Pseudomonas aeruginosa producing VIM-2 metallobeta-lactamase in Belgium. Euro Surveill 2007; 12: E070118.2. Lolans K, Queenan AM, Bush K, Sahud A, Quinn JP. First nosocomial outbreak of Pseudomonas aeruginosa producing an integron-borne metallo-b-lactamase (VIM-2) in the United States. Antimicrob Agents Chemother 2005; 49: 3538– 3540. Noue´r SA, Nucci M, de-Oliveira MP, Piffano FL, Meurer B. Risk factors for acquisition of multidrug-resistant Pseudomonas aeruginosa producing SPM metallo-b-lactamase. Antimicrob Agents Chemother 2005; 49: 3663–3667.
2007 The Authors Journal Compilation 2007 European Society of Clinical Microbiology and Infectious Diseases, CMI, 13, 1023–1035
RESEARCH NOTE Nosocomial spread of Pseudomonas aeruginosa producing the metallo-blactamase VIM-2 in a Spanish hospital: clinical and epidemiological implications C. Pen˜a1, C. Suarez1, F. Tubau2, O. Gutierrez3, A. Domı´nguez2, A. Oliver3, M. Pujol1, F. Gudiol1 and J. Ariza1 1
Infectious Diseases Service, 2Microbiology Service, IDIBELL, Hospital Universitari de Bellvitge, Barcelona and 3Microbiology Service, Hospital de Son Doreta, Palma de Mallorca, Spain
ABSTRACT Thirty-four isolates of pan-resistant Pseudomonas aeruginosa producing VIM-2 metallo-b-lactamase (MBL) were detected at a university hospital in Spain (July 2004-September 2006). Eleven (32%) patients had clinically significant infections, and three (27%) of these patients died. A single clone of MBL-producing P. aeruginosa was identified by pulsed-field gel electrophoresis. A cluster of isolates associated with the vascular surgery ward involved ten patients and appeared as a series of low-grade, sustained and misdiagnosed endemic infections in the hospital. The identification of MBL-positive P. aeruginosa should be considered mandatory in the surveillance of pan-resistant P. aeruginosa and requires a high index of suspicion in the context of endemic infections with a low attack rate. Keywords Epidemiology, metallo-b-lactamase, panresistance, Pseudomonas aeruginosa, surveillance, VIM-2 Original Submission: 16 February 2007; Revised Submission: 24 April 2007; Accepted: 2 May 2007
Clin Microbiol Infect 2007; 13: 1026–1029 10.1111/j.1469-0691.2007.01784.x
Corresponding author and reprint requests: C. Pen˜a, Infectious Diseases Service, Hospital Universitari de Bellvitge, C ⁄ Feixa Llarga s ⁄ n 08907, L’Hospitalet de Llobregat, Barcelona, Spain E-mail: [email protected]
Resistance to b-lactams, including carbapenems, in Pseudomonas aeruginosa may result from the acquisition of various b-lactamases, including metallo-b-lactamases (MBLs) [1,2]. Although MBLs were first detected in Spain in 2002 [3], very few MBL-producing P. aeruginosa (MBL-PA) strains have been found in Spain (0.08% of P. aeruginosa isolates in a recent multicentre study) (unpublished results). In the Hospital Universitari de Bellvitge (Barcelona, Spain), which is a 900-bed public institution, a cluster of pan-resistant P. aeruginosa (PR-PA) isolates producing MBLs was suspected in the vascular surgery ward in May 2005. PR-PA isolates were defined as being resistant to all b-lactam and fluoroquinolone antibiotics [4]. The phenotype of these PR-PA isolates, showing high-level resistance to all b-lactams with the exception of aztreonam, suggested the production of a carbapenem-hydrolysing MBL. From May 2005 onwards, prospective ward-based and laboratory-based surveillance was used to identify new cases of PR-PA, and clinical samples were further investigated to identify MBL producers. In addition, all PR-PA isolates from July 2004 were screened retrospectively for MBL production, and the charts of the patients with P. aeruginosa isolates that carried a transferable MBL gene (see below) were reviewed retrospectively. P. aeruginosa was identified by standard methods. MICs were initially determined using the MicroScan automated microdilution system (Dade International, West Sacramento, CA, USA) and Etests (AB Biodisk, Solna, Sweden). CLSI criteria [5] were used to define resistance. The double-disk synergy test (DDST), with ceftazidime (30 lg), imipenem (10 lg) and EDTA disks (1900 lg), was used to screen isolates for MBLs [6], and the synergy MBL Etest [7] was used to further assess MBL production. Genes encoding IMP and VIM MBLs were detected by PCR in all DDST-positive isolates, using the universal blaIMP and blaVIM primers IMP-UP, IMP-DN, VIM-B and VIM-F, respectively [8,9]. To characterise the MBL, a PCR specific for blaVIM-2 (the most prevalent MBL in southern Europe) and related genes was performed with two representative isolates. Primers VIM-2F and VIM-2R [10] were used to amplify the complete coding sequence of blaVIM-2, which was then fully sequenced for both isolates. Typing, using pulsed-field gel electrophoresis of genomic DNA digested by SpeI, was
2007 The Authors Journal Compilation 2007 European Society of Clinical Microbiology and Infectious Diseases, CMI, 13, 1023–1035
Research Notes 1027
performed for 20 blaVIM-positive P. aeruginosa isolates, representative of the entire period, with the results being interpreted as described previously [11]. Between July 2004 and September 2006, 2363 patients with P. aeruginosa-positive clinical samples were detected, with 677 (29%) yielding carbapenem-resistant isolates, of which 34 (5%) were MBL-producing isolates. Following the index case, which occurred in May 2005 in the vascular surgery ward, nine additional cases were detected prospectively. Prospective surveillance during the next 12 months revealed successful control of MBL-PA clustering in the vascular ward after reinforcement of the use of barrier precautions. Among 34 cases detected (Fig. 1), 23 (68%) were males (mean age 62 years). All isolates except one were nosocomial; the community-acquired MBL-PA isolate was from a female aged 71 years, with a chronic lung disease. The mean length of stay before isolation of MBL-PA
Vascular
ICU
was 35.6 days. Eleven (32%) patients were infected and 23 (68%) were colonised. Of the 11 infected patients, two received antibiotic therapy alone; evaluation of the efficacy of the antimicrobial therapy in the remaining nine cases was complicated by concomitant surgical drainage (Table 1). The overall mortality rate was 27%, and only one death was related to the infection as a result of multi-organ failure secondary to respiratory tract infection. The 34 isolates were highly resistant to imipenem (MIC >256 mg ⁄ L) and meropenem (MIC >32 mg ⁄ L). All isolates also demonstrated resistance to all cephalosporins, penicillins, aminoglycosides and fluoroquinolones, but were uniformly susceptible to colistin. MICs of aztreonam were lower, although ten isolates showed resistance (MIC >8 mg ⁄ L). All isolates selected, one for each patient, showed a synergic inhibition zone with the DDST, and a decrease in imipenem MIC was observed in the presence of EDTA with
Orthopaedic
Urology
Healthcare
No. of patients colonised/infected by MBL-PA
4
3
2
1
Ju A ly Se ugu 04 pt s em t 0 4 b O c er No tob 04 ve er De mb 04 ce er m 04 Ja ber n 0 Fe uar 4 br y 0 eu 5 M ry 0 ar ch 5 Ap 05 ril 0 M 5 ay Ju 05 ne Ju 05 A ly Se ug 05 pt us em t 0 O be 5 c r No tob 05 ve er De mb 05 ce er m 05 Ja ber nu 0 Fe ar 5 br y 0 eu 6 M ry 0 ar ch 6 Ap 06 ril M 06 ay Ju 06 ne Ju 06 A ly Se ug 06 pt us em t 0 be 6 r0 6
0
Cluster Retrospective study Prospective study Fig. 1. Number of patients colonised or infected with metallo-b-lactamase producing Pseudomonas aeruginosa (MBL-PA). ICU, intensive care unit. 2007 The Authors Journal Compilation 2007 European Society of Clinical Microbiology and Infectious Diseases, CMI, 13, 1023–1035
1028 Clinical Microbiology and Infection, Volume 13 Number 10, October 2007
Table 1. Clinical characteristics and outcome of 11 patients with infections caused by Pseudomonas aeruginosa isolates producing metallo-b-lactamase Patient
Date
Diagnosis at admission
Duration (days) of previous antibiotic treatment
1
July 2004
Vascular illness
CIP (20) AMC (5)
2
August 2004
Liver transplantation
ATM (5)
3
September 2004
None
4
October 2004
5
March 2005
Vascular illness Joint illness Liver transplantation Vascular illness Vascular illness Chronic renal failure Vascular illness Vascular illness Multiple trauma
6
April 2005
7
June 2005
8
June 2005
9
September 2005
10
November 2005
11
September 2006
Oesophageal perforation
CIP (11) ATM (6) MEM (7) AMC (10)
Source Vascular prosthesis, blood Catheter vascular blood Surgical wound Prosthesis, knee BAL fluid specimen Bone
Empirical antibiotic treatment
Non-antibiotic treatment
Definitive antibiotic treatment
Outcome
None
Removal of prosthesis + amputation Removal of catheter
None
Discharged
None
Death (30 days)
CIP
Amputation
None
Discharged
None
Surgical drainage –
ATM
Relapse
–
Finger amputation Amputation
None TZP
Death (1 day) Death (45 days) Discharged
Non-surgical drainage –
TZP
Discharged
ATM
Discharged
Removal of urinary catheter Surgical drainage
TZP
Discharged
AMK ATM
Discharged
TZP + AMK
MEM + AMK None
CIP (15)
Surgical wound
IMP
TZP (12)
Bone
None
CIP (23)
Bone
None
CAZ(15) IMP (14)
Urine
TZP
TZP (23) MEM (8) IMP (12)
Intra-abdominal abscess
IMP
CIP, ciprofloxacin; AMC, amoxycillin–clavulanic acid; ATM, aztreonam; MEM, meropenem; TZP, piperacillin–tazobactam; CAZ, ceftazidime; IMP, imipenem; AMK, amikacin.
the MBL Etest. Positive PCR results were obtained with the VIM primers, and sequencing confirmed the presence of blaVIM-2. An identical pulsed-field gel electrophoresis profile was found for all 20 isolates tested, including the community-acquired MBL-PA isolate. The observation of a cluster of cases involving MBL-PA isolates among vascular surgery patients revealed the presence of a low-level, insidious and sustained monoclonal endemic of MBL-PA isolates throughout the various wards of the hospital, including the intensive care units, over a relatively long period. To date, P. aeruginosa isolates with acquired MBL determinants have usually occurred sporadically or have caused small nosocomial outbreaks [8,10,12], while longitudinal surveys have demonstrated a variable level of endemicity of MBL producers [13]. VIM-2 was first identified in P. aeruginosa isolates in southern France [10], and is the most frequently acquired MBL worldwide. Similar VIM-producing P. aeruginosa strains have been described in other areas of Europe in recent years [3,14–18]. However, to our knowledge, this study is the first report of a cluster of infections caused by MBL-producing P. aeruginosa in Spain. The
similarity of the pan-resistant phenotype to that found in many non-MBL-PA isolates in the same hospital complicates the detection of MBL-producing isolates; it was not until the emergence of a cluster of cases in the vascular surgery ward that it was apparent that there was an insidious sustained monoclonal endemic occurring in the hospital. The clinical consequences of the endemic were probably only moderate, as has been suggested previously [19,20], based on the low (30%) prevalence of infected patients and an overall mortality rate of <30% in a population with severe co-morbid illness. However, the multiresistant MBL-PA isolates create important therapeutic problems and are associated with high rates of morbidity. In conclusion, the identification and surveillance of MBL-PA isolates should not be considered trivial. The difficulty of their identification in an outbreak setting, or in an endemic setting with a low attack rate, requires a high index of suspicion and the systematic inclusion of DDST and genotyping studies in nosocomial surveillance programmes for multiresistant P. aeruginosa.
2007 The Authors Journal Compilation 2007 European Society of Clinical Microbiology and Infectious Diseases, CMI, 13, 1023–1035
Research Notes 1029
ACKNOWLEDGEMENTS This work was supported by National Health Service grant FIS 03 ⁄ 0029 from the Fondo de Investigacio´n Sanitarias and also by the Ministerio de Sanidad y Consumo, the Instituto de Salud Carlos III, and the Spanish Network for the Research in Infectious Diseases (grants REIPI C03 ⁄ 14 and REIPI RD06 ⁄ 0008).
11.
12.
REFERENCES 1. Watanabe M, Iyobe S, Inoue M, Mitsuhashi S. Transferable imipenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1991; 35: 147–151. 2. Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect 2002; 8: 321–331. 3. Prats G, Miro I, Mirelis B, Poirel L, Bellais S, Nordmann P. First isolation of a carbapenem-hydrolyzing b-lactamase in Pseudomonas aeruginosa in Spain. Antimicrob Agents Chemother 2002; 46: 932–933. 4. Paterson DL. The epidemiological profile of infections with multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species. Clin Infect Dis 2006; 43 (suppl 2): S43–S48. 5. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, 16th informational supplement, document M100-S16. Wayne, PA: CLSI, 2006. 6. Lee K, Sim YS, Yong D et al. Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-b-lactamase-producing isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol 2003; 41: 4623–4629. 7. Walsh TR, Bolmstrom A, Qwarnstrom A, Gales A. Evaluation of a new Etest for detecting metallo-b-lactamases in routine clinical testing. J Clin Microbiol 2002; 40: 2755–2759. 8. Senda K, Arakawa Y, Nakashima K et al. Multifocal outbreaks of metallo-b-lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum b-lactams, including carbapenems. Antimicrob Agents Chemother 1996; 40: 349–353. 9. Lauretti L, Riccio ML, Mazzariol A et al. Cloning and characterization of blaVIM, a new integron-borne metallob-lactamase gene from a Pseudomonas aeruginosa clinical isolate. Antimicrob Agents Chemother 1999; 43: 1584–1590. 10. Poirel L, Naas T, Nicolas D et al. Characterization of VIM2, a carbapenem-hydrolyzing metallo-b-lactamase and its
13.
14.
15.
16.
17.
18.
19.
20.
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