KPC-PRODUCING Serratia marcescens IN A HOME-CARE PATIENT FROM RECIFE, BRAZIL

Serratia marcescens produtora de KPC em paciente sob assistência médica domiciliar em Recife, Brazil

SUMMARY

In this brief communication we describe the occurrence of a KPC-producing Serratia marcescensisolate in a home-care patient from Recife, Brazil. The bla_KPC, bla_SPM, bla_IMP, bla_VIMbla_OXA, bla_CTX-M, bla_SHV, bla_TEM and bla_GES genes were investigated by Polymerase Chain Reaction (PCR) and DNA sequencing. The isolate was positive for bla_KPC-2 and bla_TEM-1 and was resistant to aztreonam, cefepime, cefotaxime, imipenem, meropenem, gentamicin, ciprofloxacin and cefazidime, and susceptible only to amikacin, tigecycline and gatifloxacin. This is the first report in Brazil of KPC-producing S. marcescens clinical isolate outside of a hospital environment. Caregivers should be alert for the presence of this isolate in the community setting.

KEYWORDS:
Serratia marcescens; KPC-2 beta-lactamase; Carbapenemase; Multidrug-resistance

RESUMO

Nesse estudo descrevemos a ocorrência de um isolado de Serratia marcescensprodutor de KPC em um paciente sob assistência médica domiciliar em Recife, Brazil. Os genes bla_KPC, bla_SPM, bla_IMP, bla_VIMbla_OXA, bla_CTX-M, bla_SHV, bla_TEM and bla_GES foram investigados pela Reação em Cadeia da Polimerase (PCR) e sequenciamento de DNA. O isolado foi positivo para os genes bla_KPC-2 and bla_TEM-1 e foi resistente a aztreonam, cefepime, cefotaxima, imipenem, meropenem, gentamicina, ciprofloxacina e ceftazidima, e susceptível apenas a amicacina, tigeciclina e gatifloxacina. Este é o primeiro relato no Brasil de um isolado clínico de S. marcescensprodutor de KPC fora de ambiente hospitalar. Os profissionais de saúde devem estar atentos à presença desse isolado na comunidade.

INTRODUCTION

The emergence of Klebsiella pneumoniae carbapenemase (KPC)producing gram-negative bacteria is worrisome due to inter or intraspecies plasmid-mediated transfer of the bla_KPC gene¹⁴. Furthermore, KPC-producing isolates are commonly multidrug-resistant, reducing therapeutic options. Since the first occurrence of KPC-producing K. pneumoniae in the United States¹⁸, this enzyme has been described in several countries and in different species, mostly from nosocomial infections^{2,3,8,11,13,16}. Nevertheless, the spread of KPC-producing multidrug-resistant isolates in the community can also be a cause for great concern. In this study, we describe the emergence of the bla_KPC-2 gene in Serratia marcescens isolated outside of a hospital environment in Brazil.

MATERIAL AND METHODS

One isolate of Serratia marcescens from the tracheal aspirate of a sixty-three-year-old male with amyotrophic lateral sclerosis, diagnosed at a private laboratory in Recife, Brazil, in September, 2010, was analyzed. The patient had been receiving medical attention at home since his last hospitalization in a private hospital, in July, 2010. The isolate was initially identified by biochemical tests and confirmed using MALDI-TOF mass spectrometry methodology (Bruker Daltonics, Germanny).

Susceptibility testing was performed by the Etest (BioMérieux, Marcy l'Étoile, France) for aztreonam, cefepime, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, imipenem and meropenem, and the disk diffusion method⁶ for amikacin and gatifloxacin. Minimum inhibitory concentrations (MICs) were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The modified Hodge test (MHT) with ertapenem disks (10 µg) was used for phenotypic detection of carbapenemase activity¹².

Specific primers were used under standard PCR conditions to detect carbapenemase and ESBL encoding genes such as bla_SPM, bla_IMP,bla_VIM,

blaKPC, blaCTX-M, blaSHV, blaTEM, blaGES, blaOXA-4815, blaOXA-23, blaOXA-24, and bla_OXA-58¹⁷, followed by DNA sequencing (ABI 337 sequencer, Applied Biosystems, Foster City, CA). The nucleotide sequences were analyzed with software available at the National Center for Biotechnology Information website (http://blast.ncbi.nlm.nih.gov/Blast.cg).

RESULTS AND DISCUSSION

The Serratiamarcescens isolate was resistant to aztreonam (MIC, 128 µg/mL), cefepime (MIC, 64 µg/mL), cefotaxime (MIC, 128 µg/mL), ceftriaxone (MIC, > 32 µg/mL), imipenem and meropenem (MIC, > 32 µg/mL), gentamicin (MIC, >32 µg/mL) and ciprofloxacin (MIC, 4 µg/mL) and showed positive MHT results. On the other hand, the isolate was susceptible to amikacin and gatifloxacin, exhibiting reduced susceptibility to cefazidime (MIC, 8 µg/mL). S. marcescens carried bla_KPC-2 (GenBank accession number JX131687) and bla_TEM-1 genes (GenBank accession number JX293719).

The spread of KPC has been frequently reported in Enterobacteriaceae, mainly in K. pneumoniae. In Brazil, the occurrence of KPC-producing S. marcescens isolates was reported by DEL PELOSO et al.⁷ in intensive care unit (ICU) patients with urinary sepsis. Although the occurrence of bla_KPC-2 in S.marcescens isolates has been described in nosocomial strains^4,16, ICU patients may continue to be colonized by carbapenemase-producing isolates for long periods after hospital discharge, allowing its potential spread to households and the community^9,10. In a study conducted by CHEN et al.⁵ at a hospital in Virginia, USA, 58 patients with a mean age of 70 years were identified with infection or colonization by KPC-producing K. pneumoniae, 36% of whom were admitted from nursing homes or longterm care facilities (LTCF). The mean time to isolate a KPC-producing organism was 1.5 days after admission, suggesting that KPC-producing organisms were acquired in the community and that person-to-person transmission of KPC-producing organisms in the community is possible. GOTTESMAN et al.⁹ described extra-hospital dissemination of a KPCproducing K. pneumoniae isolate in Israel, where a patient likely acquired the isolate from his wife, who had been previously hospitalized.

In the present study, the patient probably acquired the KPC-producing S. marcescens isolate during his previous hospitalization, since he received homecare after discharge. However, we want to emphasize the occurrence of the bla_KPC gene outside the hospital environment, given that this resistance mechanism can easily spread among different species inside hospitals as well as in the community, as previously described⁹. The occurrence of KPC in community isolates of K. pneumoniae has only been reported in Brazil by ABBOUD et al.¹, in an outpatient from São Paulo.

The epidemiology of KPC-producing and multidrug-resistant organisms in a community setting remains poorly understood in Brazil. Thus, caregivers should be alert for the presence of this isolate, and prevention and control measures should be implemented not only in hospitals, but also in the community. The phenotypic and molecular characterization of community isolates can provide the essential data required to avoid the spread of this emerging resistance mechanism in the community.

REFERENCES

• ¹
  Abboud CS, Bergamasco MD, Doi AM, Zandonadi EC, Barbosa V, Cortez D, et al. First report of investigation into an outbreak due to carbapenemase-producing Klebsiella pneumoniae in a tertiary Brazilian hospital, with extension to a patient in the community. J Infect Prev. 2011;12:150-2.
• ²
  Andrade LN, Curiao T, Ferreira JC, Longo JM, Clímaco EC, Martinez R, et al.Dissemination of blaKPC-2 by the spread of Klebsiella pneumoniae clonal complex 258 clones (ST258, ST11, ST437) and plasmids (IncFII, IncN, IncL/M) among Enterobacteriaceae species in Brazil. Antimicrob Agents Chemother. 2011;55:3579-83.
• ³
  Cabral AB, Melo RC, Maciel MA, Lopes AC. Multidrug resistance genes, including bla(KPC) and bla(CTX)-M-2, among Klebsiella pneumoniae isolated in Recife, Brazil. Rev Soc Bras Med Trop. 2012;45:572-8.
• ⁴
  Cai JC, Zhou HW, Zhang R, Chen GX. Emergence of Serratia marcescens,Klebsiella pneumoniae, and Escherichia coli isolates possessing the plasmid-mediated carbapenem-hydrolyzing beta-lactamase KPC-2 in intensive care units of a Chinese hospital. Antimicrob Agents Chemother. 2008;52:2014-8.
• ⁵
  Chen LF, Anderson DJ, Paterson DL. Overview of the epidemiology and the threat of Klebsiella pneumoniae carbapenemase (KPC) resistance. Infect Drug Resist. 2012;5:133-41.
• ¹⁰
  6. CLSI. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Twentieth Informational Supplement, M100-S20. Wayne: CLSI; 2010. p. 160.
• ⁷
  Del Peloso PF, Barros MFL, Santos FA. Sepse por Serratia marcescens KPC. J Bras Patol Med Lab. 2010;46:365-7.
• ⁸
  Fehlberg LC, Carvalho AM, Campana EH, Gontijo-Filho PP, Gales AC.Emergence of Klebsiella pneumoniae-producing KPC-2 carbapenemase in Paraíba, Northeastern Brazil. Braz J Infect Dis. 2012;16:577-80.
• ⁹
  Gottesman T, Agmon O, Shwartz O, Dan M. Household transmission of carbapenemase producing Klebsiella pneumonia. Emerg Infect Dis. 2008;14:159-60.
• ¹⁰
  Heseltine P. Has resistance spread to the community?. Clin Microbiol Infect. 2000;6(Suppl 2):11-6.
• ¹¹
  Jácome PR, Alves LR, Cabral AB, Lopes AC, Maciel MA. First report of KPC-producing Pseudomonas aeruginosa in Brazil. Antimicrob Agents Chemother. 2012;56:4990.
• ¹²
  Lee K, Chong Y, Shin HB, Kim YA, Yong D, Yum JH. Modified Hodge and EDTA-disk synergy tests to screen metallo-beta-lactamase-producing strains ofPseudomonas aeruginosa and Acinetobacter species. Clin Microbiol Infect. 2001;7:88-91.
• ¹³
  Monteiro J, Santos AF, Asensi MD, Peirano G, Gales AC. First report of KPC-2producing Klebsiella pneumoniae strains in Brazil. Antimicrob Agents Chemother. 2009;53:333-4.
• ¹⁴
  Petrella S, Ziental-Gelus N, Mayer C, Renard M, Jarlier V, Sougakoff W. Genetic and structural insights into the dissemination potential of the extremely broad-spectrum class A β-lactamase KPC-2 identified in anEscherichia coli strain and an Enterobacter cloacae strain isolated from the same patient in France. Antimicrob Agents Chemother. 2011;52:3725-36.
• ¹⁵
  Picão RC, Poirel L, Gales AC, Nordmann P. Diversity of beta-lactamases produced by ceftazidima-resistant Pseudomonas aeruginosa isolates causing bloodstream infections in Brazil. Antimicrob Agents Chemother. 2009;53:3908-13.
• ¹⁶
  Tsakris A, Voulgari E, Poulou A, Kimouli M, Pournaras S, Ranellou K, et al. In vivo acquisition of a plasmid-mediated blaKPC-2 gene among clonal isolates ofSerratia marcescens. J Clin Microbiol. 2010;48:2546-9.
• ¹⁷
  Woodford N, Ellington MJ, Coelho JM, Turton JF, Ward ME, Brown S, et al. Multiplex PCR for genes encoding prevalent OXA carbapenemases inAcinetobacter spp. Int J Antimicrob Agents. 2006;27:351-3.
• ¹⁸
  Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenemresistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001;45:1151-61.

Publication Dates

• Publication in this collection
  Jul-Aug 2015

History

• Received
  23 Apr 2014
• Accepted
  11 Nov 2014