- Email: [email protected]
Cross-transmission of Klebsiella pneumoniae in two intensive care units: intra- and inter-hospital spread
Letters to the Editor / Journal of Hospital Infection 77 (2011) 274–283
Quinolone resistance was considered to be mainly mediated by the mutations of chromosomal genes, mainly gyrA and parC, encoding DNA gyrase and/or topoisomerase IV. Acinetobacter spp. clinical isolates usually mutated from Ser-83 to Leu-83 in the quinolone resistance-determining region (QRDR) of gyrA gene, and this mutation was the most common cause for the resistance to quinolones in Acinetobacter spp.5,6 In our study, mutations Ser-83 / Leu and Gly117 / Asp together with three synonymous substitutions, GGG (Gly) / GGT(Gly) at codon 71, GGC(Gly) / GGT(Gly) at codon 104 and GCC(Gla) / GCT(Gla) at codon 107, were found in gyrA of NJAb006. The sequence of gyrA has been confirmed to be a novel variant (GenBank accession number GQ892873). The patient was treated with tigecycline. Blood cultures at day 5 and day 12 were sterile. In many regions, PDR A. baumannii has been resistant to almost all antibiotics, except colistin or tigecycline. Nevertheless, resistance to colistin or tigecycline has also been documented.7 The study of Tacconelli et al. showed that the presence of central venous catheters (CVCs) was one of the risk factors for multidrug-resistant A. baumannii infections.8 In view of the implantation of a CVC before the emergence of this PDR A. baumannii isolate, NJAb006 might be associated with this.
Conflict of interest statement None declared. Funding sources None.
References 1. Chuang YY, Huang YC, Lin CH, Su LH, Wu CT. Epidemiological investigation after hospitalising a case with pandrug-resistant Acinetobacter baumannii infection. J Hosp Infect 2009;72:30–35. 2. Apisarnthanarak A, Mundy LM. Mortality associated with pandrug-resistant Acinetobacter baumannii infections in Thailand. Am J Infect Control 2009;37: 519–520. 3. Gur D, Korten V, Unal S, Deshpande LM, Castanheira M. Increasing carbapenem resistance due to the clonal dissemination of oxacillinase (OXA-23 and OXA-58)producing Acinetobacter baumannii: report from the Turkish SENTRY Program sites. J Med Microbiol 2008;57:1529–1532. 4. Galimand M, Courvalin P, Lambert T. Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrobial Agents Chemother 2003;47:2565–2571. 5. Mak JK, Kim MJ, Pham J, Tapsall J, White PA. Antibiotic resistance determinants in nosocomial strains of multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 2009;63:47–54. 6. Sheng WH, Lin YC, Wang JT, et al. Identification of distinct ciprofloxacin susceptibility in Acinetobacter spp. by detection of the gyrA gene mutation using real-time PCR. Mol Cell Probes 2009;23:154–156. 7. Garnacho-Montero J, Amaya-Villar R. Multiresistant Acinetobacter baumannii infections: epidemiology and management. Curr Opin Infect Dis 2010;23: 332–339. 8. Tacconelli E, Cataldo MA, De Pascale G, et al. Prediction models to identify hospitalized patients at risk of being colonized or infected with multidrug-resistant Acinetobacter baumannii calcoaceticus complex. J Antimicrob Chemother 2008; 62:1130–1137.
W.S. Zhaoa G.Y. Liua Z.H. Mib F. Zhangc,* a Clinical Laboratory Department of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China b
Wuxi Clone Gen-Tech Institute, Wuxi, China
c
Clinical Laboratory Department of the Third Affiliated Hospital, Nantong University, Wuxi, China
*
279
Corresponding author. Address: Clinical Laboratory Department of the Third Affiliated Hospital, Nantong University, Xing Yuan North Road 585, Wuxi, Jiangsu 214041, China. E-mail address: [email protected] (F. Zhang). Available online 1 February 2011
Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2010.11.006
Cross-transmission of Klebsiella pneumoniae in two intensive care units: intra- and inter-hospital spread Madam, The results of the first edition of the Italian Nosocomial Infections Surveillance in Intensive Care Units (SPIN-UTI) project revealed that Klebsiella pneumoniae is one of the most commonly isolated micro-organisms in intensive care unit (ICU)-acquired infections.1 Due to this, in order to identify, assess and apply relevant evidence for better healthcare decision-making, in the framework of the second edition of the SPIN-UTI project, from October 2008 to May 2009, a specific surveillance programme for K. pneumoniae acquisition, integrating the patient-based and the laboratory-based surveillance approaches, was implemented in two interdisciplinary ICUs, at the Azienda Ospedaliero-Universitaria Vittorio Emanuele-Ferrarotto-S. Bambino (OVE) and at the Azienda Ospedaliera Cannizzaro (AOC), Catania, Italy. The surveillance protocol was described in greater detail elsewhere.1 Patients with positive screening cultures in the absence of, or before isolation of, positive clinical specimens were considered to be carriers. In the case of a lack of clinical data confirming infection, patients with positive clinical specimens were considered to be colonised.2 Standard definitions of healthcare-associated infections were used.1 Furthermore, isolates from patients not included in the SPIN-UTI project were assigned to colonisation/ infection episodes as defined by the presence of K. pneumoniae in clinical specimens, since the criteria for infection were not registered. During the study period, a total of 108 K. pneumoniae isolates were collected from 54 patients. A summary of SPIN-UTI patients’ characteristics and the epidemiological patterns of K. pneumoniae acquisition in the two ICUs are shown in Table I. In particular, comparing incidence and incidence density of K. pneumoniae-sustained infections with historic data from the first edition of the SPIN-UTI project, in the two ICUs, the incidence of K. pneumoniae increased from 5.1% to 22.8% (OVE) and from 5.0% to 14.7% (AOC). Incidence densities of K. pneumoniae-sustained infections increased from 2.2 and 1.7 per 1000 patientdays to 3.0 and 8.8 per 1000 patient-days, respectively in the two ICUs. The increased K. pneumoniae-sustained infection rates might be due to transmission of resistant pathogens between patients and this should be reflected by the predominance of certain genotypes. Molecular typing by pulsed-field gel electrophoresis (PFGE) of K. pneumoniae isolates led to the identification of four clones associated with cross-transmission and 23 clones as sporadic strains. Two major clones were identified; clone A was present
280
Letters to the Editor / Journal of Hospital Infection 77 (2011) 274–283
Table I Main characteristics of patients included in the study and epidemiological patterns of K. pneumoniae acquisition in the two intensive care units (ICUs) OVE No. of patients Mean age, years (range) Male (%) SAPS II score Mean length of stay in days (range) Total length of stay (days) Mechanical ventilation (%) Urinary catheter (%) Central line catheter (%) No. of isolates No. of patients with K. pneumoniae acquisition Total length of stay (days) No. of carriage events at admission (no. of patients) No. of colonisation/infection episodes (no. of patients) No. of colonisation episodes (no. of patients) ICU-acquired colonisation (/100 patients) Incidence density of colonisation (/1000 patient-days) No. of infection episodes (no. of patients) ICU-acquired infection (/100 patients) Incidence density of infection (/1000 patient-days)
AOC
91 62.6 (1–97) 56.0 27.4 (6–62) 7.2 (3–72) 1335 92.3 100 96.7 13 10 1335 1 (1) 2 (2) 6 (6) 6.6 4.5 4 (4) 4.4 3.0
Total
80 59.3 (22–92) 53.8 51.6 (16–87) 20 (3–106) 1598 97.5 100 100 95 44 1598 11 (10) 28 (20) 20 (15) 25.0 12.5 14 (9) 17.5 8.8
171 61.1 (1–97) 55.5 39.9 (6–87) 17.2 (3–106) 2933 92.6 100 97.2 108 54 2933 12 (11) 30 (22) 26 (21) 15.2 8.9 18 (13) 10.5 6.1
OVE, Azienda Ospedaliero-Universitaria Vittorio Emanuele-Ferrarotto-S. Bambino; AOC, Azienda Ospedaliera Cannizzaro; SAPS II, new Simplified Acute Physiology Score.
in 38.9% of patients with K. pneumoniae isolation from both ICUs, showing inter-hospital spread, and clone E was present in 29.6% of patients with K. pneumoniae isolates all admitted to the AOC, showing intra-hospital spread, as previously reported elsewhere.3 The epidemic curve for each ICU suggested the occurrence of propagated transmission, probably associated with person-to-person contact. The impact of confirmed K. pneumoniae cross-transmission episodes was at least 61.5% in the OVE and 38.4% in the AOC, thus defining the exogenous preventable proportion of all cross-transmission episodes. The outbreak developed despite ongoing active surveillance and contact precautions but was ultimately controlled by reinforced infection control measures without closing the ICUs to new admissions. In particular, to achieve containment of outbreaks, infection control measures were intensified throughout the ICUs, e.g. monitoring of compliance with hand hygiene, contact isolation measures and adherence of personnel to environmental cleaning. Furthermore, meetings between ICU staff and infection control teams were held every week to give information on the number of new isolates and to monitor the implementation and optimisation of infection control measures. Multivariate logistic regression analysis, used to adjust for possible confounding factors such as length of stay, showed that K. pneumoniae isolation was significantly asociated with death in the ICU (odds ratio: 2.7; 95% confidence interval: 1.1–6.9; P ¼ 0.032). These results have important implications for the prevention, detection, and treatment of K. pneumoniae infection, strengthening recent findings from other institutions.4 In conclusion, our results underline the impact of K. pneumoniae in the ICU settings and highlight the need for appropriate and continuous epidemiological investigations to trace sources and transmission routes in order to address control policies to contain nosocomial transmission of this micro-organism.
References 1. Agodi A, Auxilia F, Barchitta M, Brusaferro S, D’Alessandro D, Montagna MT, et al. Building a benchmark through active surveillance of ICU-acquired infections: the Italian network SPIN-UTI. J Hosp Infect 2010;74:258–265. 2. Agodi A, Barchitta M, Cipresso R, Giaquinta L, Romeo MA, Denaro C. Pseudomonas aeruginosa carriage, colonization, and infection in ICU patients. Intens Care Med 2007;33:1155–1161. 3. Souli M, Galani I, Antoniadou A, Papadomichelakis E, Poulakou G, Panagea T, et al. An outbreak of infection due to b-lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek university hospital: molecular characterization, epidemiology, and outcomes. Clin Infect Dis 2010;50:364–373. 4. Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 2008;52:1028–1033.
A. Agodia,* M. Barchittaa G. Valentia M.A. Romeob L. Giaquintab C. Santangeloc G. Castiglionec A. Tsakrisd a Department of Biomedical Sciences, University of Catania, Italy b
Azienda Ospedaliera Cannizzaro, Catania, Italy
c
Azienda Ospedaliero-Universitaria ‘Policlinico-Vittorio Emanuele’, Catania, Italy
d
Department of Microbiology, Medical School, University of Athens, Athens, Greece * Corresponding author. Address: Department of Biomedical Sciences, University of Catania, Italy, Via S. Sofia n. 87 – 95123 Catania, Italy. Tel./fax: þ39 095 3782076. E-mail address: [email protected] (A. Agodi). Available online 28 January 2011
Conflict of interest statement None declared. Funding sources This work was supported in part by grants from the University of Catania (Progetti di Ricerca di Ateneo to A.A.) and the University of Athens (to A.T.).
Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2010.10.007
Quinolone resistance was considered to be mainly mediated by the mutations of chromosomal genes, mainly gyrA and parC, encoding DNA gyrase and/or topoisomerase IV. Acinetobacter spp. clinical isolates usually mutated from Ser-83 to Leu-83 in the quinolone resistance-determining region (QRDR) of gyrA gene, and this mutation was the most common cause for the resistance to quinolones in Acinetobacter spp.5,6 In our study, mutations Ser-83 / Leu and Gly117 / Asp together with three synonymous substitutions, GGG (Gly) / GGT(Gly) at codon 71, GGC(Gly) / GGT(Gly) at codon 104 and GCC(Gla) / GCT(Gla) at codon 107, were found in gyrA of NJAb006. The sequence of gyrA has been confirmed to be a novel variant (GenBank accession number GQ892873). The patient was treated with tigecycline. Blood cultures at day 5 and day 12 were sterile. In many regions, PDR A. baumannii has been resistant to almost all antibiotics, except colistin or tigecycline. Nevertheless, resistance to colistin or tigecycline has also been documented.7 The study of Tacconelli et al. showed that the presence of central venous catheters (CVCs) was one of the risk factors for multidrug-resistant A. baumannii infections.8 In view of the implantation of a CVC before the emergence of this PDR A. baumannii isolate, NJAb006 might be associated with this.
Conflict of interest statement None declared. Funding sources None.
References 1. Chuang YY, Huang YC, Lin CH, Su LH, Wu CT. Epidemiological investigation after hospitalising a case with pandrug-resistant Acinetobacter baumannii infection. J Hosp Infect 2009;72:30–35. 2. Apisarnthanarak A, Mundy LM. Mortality associated with pandrug-resistant Acinetobacter baumannii infections in Thailand. Am J Infect Control 2009;37: 519–520. 3. Gur D, Korten V, Unal S, Deshpande LM, Castanheira M. Increasing carbapenem resistance due to the clonal dissemination of oxacillinase (OXA-23 and OXA-58)producing Acinetobacter baumannii: report from the Turkish SENTRY Program sites. J Med Microbiol 2008;57:1529–1532. 4. Galimand M, Courvalin P, Lambert T. Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrobial Agents Chemother 2003;47:2565–2571. 5. Mak JK, Kim MJ, Pham J, Tapsall J, White PA. Antibiotic resistance determinants in nosocomial strains of multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 2009;63:47–54. 6. Sheng WH, Lin YC, Wang JT, et al. Identification of distinct ciprofloxacin susceptibility in Acinetobacter spp. by detection of the gyrA gene mutation using real-time PCR. Mol Cell Probes 2009;23:154–156. 7. Garnacho-Montero J, Amaya-Villar R. Multiresistant Acinetobacter baumannii infections: epidemiology and management. Curr Opin Infect Dis 2010;23: 332–339. 8. Tacconelli E, Cataldo MA, De Pascale G, et al. Prediction models to identify hospitalized patients at risk of being colonized or infected with multidrug-resistant Acinetobacter baumannii calcoaceticus complex. J Antimicrob Chemother 2008; 62:1130–1137.
W.S. Zhaoa G.Y. Liua Z.H. Mib F. Zhangc,* a Clinical Laboratory Department of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China b
Wuxi Clone Gen-Tech Institute, Wuxi, China
c
Clinical Laboratory Department of the Third Affiliated Hospital, Nantong University, Wuxi, China
*
279
Corresponding author. Address: Clinical Laboratory Department of the Third Affiliated Hospital, Nantong University, Xing Yuan North Road 585, Wuxi, Jiangsu 214041, China. E-mail address: [email protected] (F. Zhang). Available online 1 February 2011
Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2010.11.006
Cross-transmission of Klebsiella pneumoniae in two intensive care units: intra- and inter-hospital spread Madam, The results of the first edition of the Italian Nosocomial Infections Surveillance in Intensive Care Units (SPIN-UTI) project revealed that Klebsiella pneumoniae is one of the most commonly isolated micro-organisms in intensive care unit (ICU)-acquired infections.1 Due to this, in order to identify, assess and apply relevant evidence for better healthcare decision-making, in the framework of the second edition of the SPIN-UTI project, from October 2008 to May 2009, a specific surveillance programme for K. pneumoniae acquisition, integrating the patient-based and the laboratory-based surveillance approaches, was implemented in two interdisciplinary ICUs, at the Azienda Ospedaliero-Universitaria Vittorio Emanuele-Ferrarotto-S. Bambino (OVE) and at the Azienda Ospedaliera Cannizzaro (AOC), Catania, Italy. The surveillance protocol was described in greater detail elsewhere.1 Patients with positive screening cultures in the absence of, or before isolation of, positive clinical specimens were considered to be carriers. In the case of a lack of clinical data confirming infection, patients with positive clinical specimens were considered to be colonised.2 Standard definitions of healthcare-associated infections were used.1 Furthermore, isolates from patients not included in the SPIN-UTI project were assigned to colonisation/ infection episodes as defined by the presence of K. pneumoniae in clinical specimens, since the criteria for infection were not registered. During the study period, a total of 108 K. pneumoniae isolates were collected from 54 patients. A summary of SPIN-UTI patients’ characteristics and the epidemiological patterns of K. pneumoniae acquisition in the two ICUs are shown in Table I. In particular, comparing incidence and incidence density of K. pneumoniae-sustained infections with historic data from the first edition of the SPIN-UTI project, in the two ICUs, the incidence of K. pneumoniae increased from 5.1% to 22.8% (OVE) and from 5.0% to 14.7% (AOC). Incidence densities of K. pneumoniae-sustained infections increased from 2.2 and 1.7 per 1000 patientdays to 3.0 and 8.8 per 1000 patient-days, respectively in the two ICUs. The increased K. pneumoniae-sustained infection rates might be due to transmission of resistant pathogens between patients and this should be reflected by the predominance of certain genotypes. Molecular typing by pulsed-field gel electrophoresis (PFGE) of K. pneumoniae isolates led to the identification of four clones associated with cross-transmission and 23 clones as sporadic strains. Two major clones were identified; clone A was present
280
Letters to the Editor / Journal of Hospital Infection 77 (2011) 274–283
Table I Main characteristics of patients included in the study and epidemiological patterns of K. pneumoniae acquisition in the two intensive care units (ICUs) OVE No. of patients Mean age, years (range) Male (%) SAPS II score Mean length of stay in days (range) Total length of stay (days) Mechanical ventilation (%) Urinary catheter (%) Central line catheter (%) No. of isolates No. of patients with K. pneumoniae acquisition Total length of stay (days) No. of carriage events at admission (no. of patients) No. of colonisation/infection episodes (no. of patients) No. of colonisation episodes (no. of patients) ICU-acquired colonisation (/100 patients) Incidence density of colonisation (/1000 patient-days) No. of infection episodes (no. of patients) ICU-acquired infection (/100 patients) Incidence density of infection (/1000 patient-days)
AOC
91 62.6 (1–97) 56.0 27.4 (6–62) 7.2 (3–72) 1335 92.3 100 96.7 13 10 1335 1 (1) 2 (2) 6 (6) 6.6 4.5 4 (4) 4.4 3.0
Total
80 59.3 (22–92) 53.8 51.6 (16–87) 20 (3–106) 1598 97.5 100 100 95 44 1598 11 (10) 28 (20) 20 (15) 25.0 12.5 14 (9) 17.5 8.8
171 61.1 (1–97) 55.5 39.9 (6–87) 17.2 (3–106) 2933 92.6 100 97.2 108 54 2933 12 (11) 30 (22) 26 (21) 15.2 8.9 18 (13) 10.5 6.1
OVE, Azienda Ospedaliero-Universitaria Vittorio Emanuele-Ferrarotto-S. Bambino; AOC, Azienda Ospedaliera Cannizzaro; SAPS II, new Simplified Acute Physiology Score.
in 38.9% of patients with K. pneumoniae isolation from both ICUs, showing inter-hospital spread, and clone E was present in 29.6% of patients with K. pneumoniae isolates all admitted to the AOC, showing intra-hospital spread, as previously reported elsewhere.3 The epidemic curve for each ICU suggested the occurrence of propagated transmission, probably associated with person-to-person contact. The impact of confirmed K. pneumoniae cross-transmission episodes was at least 61.5% in the OVE and 38.4% in the AOC, thus defining the exogenous preventable proportion of all cross-transmission episodes. The outbreak developed despite ongoing active surveillance and contact precautions but was ultimately controlled by reinforced infection control measures without closing the ICUs to new admissions. In particular, to achieve containment of outbreaks, infection control measures were intensified throughout the ICUs, e.g. monitoring of compliance with hand hygiene, contact isolation measures and adherence of personnel to environmental cleaning. Furthermore, meetings between ICU staff and infection control teams were held every week to give information on the number of new isolates and to monitor the implementation and optimisation of infection control measures. Multivariate logistic regression analysis, used to adjust for possible confounding factors such as length of stay, showed that K. pneumoniae isolation was significantly asociated with death in the ICU (odds ratio: 2.7; 95% confidence interval: 1.1–6.9; P ¼ 0.032). These results have important implications for the prevention, detection, and treatment of K. pneumoniae infection, strengthening recent findings from other institutions.4 In conclusion, our results underline the impact of K. pneumoniae in the ICU settings and highlight the need for appropriate and continuous epidemiological investigations to trace sources and transmission routes in order to address control policies to contain nosocomial transmission of this micro-organism.
References 1. Agodi A, Auxilia F, Barchitta M, Brusaferro S, D’Alessandro D, Montagna MT, et al. Building a benchmark through active surveillance of ICU-acquired infections: the Italian network SPIN-UTI. J Hosp Infect 2010;74:258–265. 2. Agodi A, Barchitta M, Cipresso R, Giaquinta L, Romeo MA, Denaro C. Pseudomonas aeruginosa carriage, colonization, and infection in ICU patients. Intens Care Med 2007;33:1155–1161. 3. Souli M, Galani I, Antoniadou A, Papadomichelakis E, Poulakou G, Panagea T, et al. An outbreak of infection due to b-lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek university hospital: molecular characterization, epidemiology, and outcomes. Clin Infect Dis 2010;50:364–373. 4. Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 2008;52:1028–1033.
A. Agodia,* M. Barchittaa G. Valentia M.A. Romeob L. Giaquintab C. Santangeloc G. Castiglionec A. Tsakrisd a Department of Biomedical Sciences, University of Catania, Italy b
Azienda Ospedaliera Cannizzaro, Catania, Italy
c
Azienda Ospedaliero-Universitaria ‘Policlinico-Vittorio Emanuele’, Catania, Italy
d
Department of Microbiology, Medical School, University of Athens, Athens, Greece * Corresponding author. Address: Department of Biomedical Sciences, University of Catania, Italy, Via S. Sofia n. 87 – 95123 Catania, Italy. Tel./fax: þ39 095 3782076. E-mail address: [email protected] (A. Agodi). Available online 28 January 2011
Conflict of interest statement None declared. Funding sources This work was supported in part by grants from the University of Catania (Progetti di Ricerca di Ateneo to A.A.) and the University of Athens (to A.T.).
Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2010.10.007