The increased frequency and dissemination of enterobacteria resistant to various antimicrobials is currently worldwide concern. In January 2010, a 94-year-old patient with chronic lymphocytic leukemia was admitted to the University Hospital. This patient died 21 days after hospitalization due to the clinical worsening. Klebsiella pneumoniae producing of extended-spectrum β-lactamases (ESBLs) was isolated of urine culture. This bacterium demonstrated resistance to ceftazidime, ciprofloxacin, levofloxacin, ertapenem and imipenem. Susceptibility to cefoxitin, cefepime, meropenem, colistin and tigecycline. This study reports the first case of infection by Klebsiella pneumoniae carrying the bla kpc gene in the State of Mato Grosso do Sul, Brazil.
Carbapenemase; Klebsiella pneumoniae ; Multidrug- resistant
The emergence of β-lactamases producing enterobacteria has been considered one of the major challenges faced by hospitals in recent decades. Recent reports have shown an increasing prevalence of these enterobacteria, especially Klebsiella pneumoniae strains resistant to carpabenens, antibiotics indicated for the treatment of patients who are infected with bacteria producing extended-spectrum β-lactamases (ESBLs)1.
The Klebsiella pneumoniae carbapenemase (KPC-KPN) was first described in 1996 in North Carolina, USA2. In Brazil, the first reports of KPC-KPN infection among Northeastern patients were described in 20063. However, there is also evidence that the carpabenem-resistant genotype was described in 2005 in São Paulo4. Since then, this microorganism has been disseminate to several hospitals in different Brazilian states5-7.
In January 2010, a 94-year-old female patient who had been diagnosed with chronic lymphocytic leukemia was hospitalized in a teaching hospital with 256 beds in Campo Grande, State of Mato Grosso do Sul, Midwest Brazil. This patient presented with the following symptoms: a cough with sputum production, hoarseness, sibilance, dyspnea and a fever of 39ºC. The patients' blood pressure and glycemia were normal. Antibiotic therapy, consisting of ceftriaxone 1g twice daily, and clindamycin 600mg three times a day for 10 days. During the period of hospitalization, she developed a urinary tract infection, and there was a concomitant worsening of her laboratorial results and clinical condition. The antimicrobial therapy was first switched to ciprofloxacin and piperacilin/tazobactam and was subsequently included vancomycin and fluconazole (yeast in the urine) due to the patient's persistent clinical worsening. However, the patient died 21 days after hospitalization.
The patient had used a central venous catheter for 17 days, and a three-way catheter was used for vesical catheterization over the course of 19 days, with three removals. The urine samples collected at 12 and 15 days post-hospitalization resulted in positive cultures containing greater than 105 UFC/mL (colony forming units/mL) Klebsiella pneumoniae was isolated, and the result of the Modified Hodge Test was positive. Moreover, the results produced by the VITEK 2 automated system (bioMérieux, Marcy l'Etoile, France) revealed that the patothogen was producing ESBLs and demonstrated resistance to ceftazidime, the fluoroquinolones ciprofloxacin and levofloxacin, and the carbapenemic ertapenem and imipenem and susceptibility to cefoxitin, cefepime, meropenem, colistin and tigecycline (Table 1).
Antimicrobial susceptibility profile of the Klebsiella pneumoniae strain isolated from the patient's urine culture.
The first positive urine culture sample was sent to the Laboratório Especial de Microbiologia Clínica da Universidade Federal de São Paulo, where bla kpc-2 gene was detected by polymerase chain reaction analysis followed by deoxyribonucleic acid (DNA) sequencing3. The study was approved by the Research Ethics Committee of Universidade Federal de Mato Grosso do Sul (UFMS).
The clonal dissemination of KPC-KPN strains across hospitals throughout the world has been documented7,8. Since the first description in 2009, which was made by Monteiro et al.3, sporadic cases and outbreaks have been reported in Brazil5,9. The case presented here represents the first report of infection with Klebsiella pneumoniaebcarrying the bla kpc gene in the State of Mato Grosso do Sul, Midwest Brazil.
Between 2009 and 2010, an increased number of notifications were made to the Agência Nacional de Vigilância Sanitária (ANVISA) concerning outbreaks in different regions of the country, which generated a national response. Faced with this situation, ANVISA published a technical standard in an attempt to control the dissemination of these multidrug-resistant microrganisms10. The dissemination of resistant strains mainly results from the lack or failure of proper therapeutic treatments, and the results of such dissemination can be catastrophic if effective control measures are not undertaken.
Infections caused by multidrug-resistant enterobacteriaceae tend to be more frequent among elderly patients with impaired immune systems. This is especially true for those who have other comorbidities5, such as the patient described here, who was elderly and also had chronic lymphocytic leukemia. Moreover, these types of infections are usually associated with high lethality5,8.
According to the literature, invasive procedures, such as the use of central venous catheters or urinary catheters, are significant routes of infection resulting from healthcare interventions11. In the cases reported by Beirão et al.5, all of the patients diagnosed with KPC-KPN infections, which had been isolated from the urine, had been given urinary catheters.
It is important to note that the minimum inhibitory concentration (CIM) for meropenem from the sample of KPC-KPN was characterized as susceptible according to the Clinical and Laboratory Standards Institute (CLSI) criteria12, which indicates a risk of therapeutic failure for cases of infection treated with this antimicrobial.
Health surveillance studies and molecular analyses aimed at identifying antibiotic resistance genes are required for optimal detection of the emergence and occurrence of future KPC-KPN outbreaks. Moreover, such analyses and studies may also identify the likelihood of further dissemination of these genes in Brazil.
1Abreu AG, Marques SG, Monteiro-Neto V, Carvalho RML, Gonçalves AG. Nosocomial infection and characterization of extended-spectrum â-lactamases-producing Enterobacteriaceae in Northeast Brazil. Rev Soc Bras Med Trop 2011; 44:441-446.
2Yigit H, Queenan AM, Anderson GJ, Domenich-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001; 45:1151-1161.
3Monteiro J, Santos AF, Asensi MD, Peirano G, Gales AC. First Report of KPC-2-Producing Klebsiella pneumoniae Strains in Brazil. Antimicrob Agents Chemother 2009; 53:333-334.
4Pavez M, Mamizuka EM, Lincopan N. Early Dissemination of KPC-2-Producing Klebsiella pneumoniae Strains in Brazil. Antimicrob Agents Chemother 2009; 53:2702.
5Beirão EM, Furtado JJD, Girardello R, Ferreira Filho H, Gales AC. Clinical and microbiological characterization of KPC-producing Klebsiella pneumoniae infections in Brazil. Braz J Infect Dis 2011; 15:69-73.
6Zavascki AP, Zoccolic CM, Machado ABMP, Oliveira KRP, Supertie SV, Pilgerf DA, et al. KPC-2-producing Klebsiella pneumoniae in Brazil: A widespread threat in waiting? Int J Med Microbiol 2009: 539-540.
7Seki ML, Pereira OS, Souza MPAH, Conceição MS, Marques EA, Porto COP, et al. Molecular epidemiology of KPC- 2- producing Klebsiella pneumoniae isolates in Brazil: the predominance of sequence type 437. Diagn Microbiol Infect Dis 2011; 70:274-277.
8Nordmann P, Cuzon G, Naas T. The real threat of Klbesiella pneumonia carbapenemase- producing bacteria. Lancet Infect Dis 2009; 9:228-236.
9Peirano G, Seki LM, Val Passos VR, Pinto MCFG, Guerra LR, Asensi MD. Carbapenem-hydrolysing b-lactamase KPC-2 in Klebsiella pneumoniae isolated in Rio de Janeiro, Brazil. J Antimicrob Chemother 2008; 63:265-268.
10Agencia Nacional de Vigilância Sanitária. Medidas para identificação, prevenção e controle de infecções relacionadas à assistência à saúde por microrganismos multirresistentes. Technical Note n 1/2010. Brasília: Ministério da Saúde; 2010.
11Menashe G, Borer A, Yagupsky P, Peled N, Gilad J, Fraser D, et al. Clinical significance and impact on mortality of extended- spectrum beta lactamase - producing Enterobacteriaceae isolates in nosocomial bacteremia. Scand J Infect Dis 2001; 33:188- 193.
12Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing M100-S21. Wayne, USA: CLSI; 2011.
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