Post-neurosurgical meningitis caused by KPC-producing Klebsiella pneumoniae: report of two cases

Yasmin Coelho Patrial Luma Petri Tortorelli Ana Claudia Souza Rodrigues Ivson Cassiano de Oliveira Santos Cláudia Elizabeth Volpe-Chaves Gislaine Souza Capato Gustavo Augusto Ribeiro Barbosa Ana Paula D’Alincourt Carvalho-Assef Marilene Rodrigues Chang About the authors

ABSTRACT

Nosocomial bacterial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is associated with high mortality in neurosurgical patients. There are few reports in the literature on meningitis caused by CRKP. We report two cases of CRKP meningitis after neurosurgery. The K. pneumoniae identification and antimicrobial susceptibility testing were performed using the Vitek Compact System. Minimum inhibitory concentrations of polymyxin B were determined using the broth microdilution method. Molecular typing of K. pneumoniae isolates was investigated using multilocus sequence typing. Antimicrobial susceptibility testing showed that the K. pneumoniae isolates were multidrug resistant and co-produced extended-spectrum β-lactamases and KPC enzymes. The patients were treated with intrathecal polymyxin. Genetic polymorphism analyses revealed two different K. pneumoniae clones (ST1298 and ST2687), which were observed for the first time in CRKP infections. We recommend intravenous administration of intrathecal polymyxin for treating meningitis caused by multidrug-resistant K. pneumoniae .

Meningitis; Klebsiella pneumoniae; Carbapenem-resistant; Beta-lactamases; Cerebrospinal fluid

INTRODUCTION

Meningitis refers to several infections defined as inflammation of the meninges; it may be caused by various infectious agents, including bacteria, viruses, parasites, fungi and non-infectious processes. Although viral meningitis is the most common, bacterial meningitis may be more severe and potentially life-threatening11. Hasbun R, Rosenthal N, Balada-Llasat JM, Chung J, Duff S, Bozzette S, et al. Epidemiology of meningitis and encephalitis in the United States, 2011–2014. Clin Infect Dis. 2017;65:359-63. . In recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has become endemic and is one of the biggest public health concerns globally22. Pereira PS, Araujo CF, Seki LM, Zahner V, Carvalho-Assef AP, Asensi MD. Update of the molecular epidemiology of KPC-2-producing Klebsiella pneumoniae in Brazil: spread of clonal complex 11 (ST11, ST437 and ST340). J Antimicrob Chemother. 2012;68:312-6. , 33. Tängdén T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. J Intern Med. 2015;277:501-12. . However, there are few reports in the literature on meningitis caused by CRKP44. Almeida SM, Nogueira KS, Palmeiro JK, Scheffer MC, Stier CJ, França JC, et al. Nosocomial meningitis caused by Klebsiella pneumonia producing carbapenemase, with initial cerebrospinal fluid minimal inflammatory response. Arq Neuropsiquiat. 2014;72:398-9. , 55. Holyk A, Belden V, Lee JJ, Musick W, Keul R, Britz GW, et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Antimicrob Chemother. 2018;73:254-6. . We report two cases of post-neurosurgical nosocomial meningitis due to CRKP that were successfully treated with polymyxin.

MATERIALS AND METHODS

Clinical data were obtained from medical records. Bacterial identification and antimicrobial susceptibility testing were performed using the Vitek 2 Compact System® (bioMérieux, Marcy L’Étoile, France). The polymyxin B minimum inhibitory concentrations (MICs) were determined using the reference Clinical Laboratory Standards Institute broth microdilution method66. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: 22thinformational supplement (M100-S27). Wayne: CLSI; 2017. . Genes coding for extended-spectrum β-lactamases ( bla -CTX-M, bla -TEM, bla -SHV), carbapenemases ( bla -KPC, bla -OXA-48), and metallo-β-lactamases ( bla -NDM-1, bla -IMP, bla -VIM) were investigated using the polymerase chain reaction, as described previously77. Monteiro J, Widen RH, Pignatari AC, Kubasek C, Silbert S. Rapid detection of carbapenemase genes by multiplex real-time PCR. J Antimicrob Chemother. 2012;67:906-9.

8. Senda K, Arakawa Y, Ichiyama S, Nakashima K, Ito H, Ohsuka S, et al. PCR detection of metallo-beta-lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum beta-lactams. J Clin Microbiol. 1996;34:2909-13.
- 99. Oliveira CF, Dal Forno NL, Alves IA, Horta JA, Rieger A, Alves SH. Prevalence of the TEM, SHV and CTX-M families of extended-spectrum [beta]-lactamases in Escherichia coli and Klebsiella spp at the University Hospital of Santa Maria, State of Rio Grande do Sul. Rev Soc Bras Med Trop. 2009;42:556-60. . Molecular typing was performed by multilocus sequence typing (MLST)1010. Diancourt L, Passet V, Verhoef J, Grimont PA, Brisse S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol. 2005;43:4178-82. .

CASE REPORTS

Case 1

A 17-year-old man from Campo Grande, Mato Grosso do Sul State, Brazil, was admitted to the emergency room after a car accident. On admission, the patient was sedated and intubated and had a heart rate of 90 beats/min, respiratory rate of 17 breaths/min, arterial blood pressure of 160/90 mmHg, Glasgow Coma Scale (GCS) score of 3/15 and APACHE index of 17. The skull computed tomography (CT) revealed cerebral edema with post-traumatic hydrocephalus, frontal lobe contusion and subarachnoid hemorrhage (grade IV on the Fisher scale).

An external ventricular shunt was inserted. The patient developed anisocoria and miotic pupils. Besides diffuse edema noted on a new CT, decompressive craniotomy was necessary. He also underwent various invasive procedures during hospitalization, including tracheostomy, central venous catheterization, urinary catheterization, enteral nutrition and mechanical ventilation. On postoperative day 3, the patient developed septic shock, probably from skin and fascial breast foci. Cerebrospinal fluid (CSF) examination revealed no abnormalities ( Table 1 ). However, head CT revealed opacification of the left maxillary and ethmoidal sinuses. Intravenous (IV) meropenem, 1 g/8 h was administered. Clinical improvement and of the consciousness level was noted (GCS 8). On hospitalization day 11, his level of consciousness deteriorated again (GCS score decreased to 3/15); he presented with hyperthermia (38.8 ºC), arterial hypertension (153/90 mmHg), and leukocytosis (leukocytes 39,600/mm33. Tängdén T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. J Intern Med. 2015;277:501-12. , with 84% segmented and 4% rods). New CSF analysis showed lymphocytic pleocytosis that was culture positive to K. pneumoniae , which was resistant to most antibiotics tested, including all β-lactams and gentamicin. However, it was susceptible to amikacin, ciprofloxacin and polymyxin (MIC=0.25). Analysis of β-lactamase genes revealed the presence of bla- TEM, bla- SHV, and bla- KPC genes. The isolate was identified as sequence type 1298.

Table 1
Case 1 cerebrospinal fluid characteristics compatible with an acute bacterial meningitis caused by a KPC-producing K. pneumoniae.

Because of his clinical condition and decreasing consciousness level, IV polymyxin E 150 mg/12 h was added to his treatment for 19 days. Meropenem was maintained following CSF culture results, with the dose increased to 2 g/8 h. Despite improved CSF parameters, intrathecal polymyxin E (5 mg/day for 3 days and then every other day to complete 7 days of treatment) was introduced. The patient was discharged 37 days after admission with a GCS score of 15 and no CSF abnormalities ( Table 1 ).

Case 2

A 50-year-old woman from Sao Gabriel do Oeste, Mato Grosso do Sul State (MS), Brazil, presented with severe traumatic brain injury and loss of consciousness after a fall from her own height. The Emergency Mobile Care Service classified the patient as having a severe condition with a cephalic contusion of 3 cm, GCS score of 7/15, anisocoric pupils, normal blood pressure (110/70 mmHg) and normal cardiopulmonary auscultation. She had a history of mental disorder due to cerebral palsy, arterial hypertension and diabetes mellitus.

The patient was transferred to a tertiary hospital in Campo Grande, MS. On admission, she was sedated and intubated after first aid. She had a GCS score of 4/15, isochoric pupils, lack of motor response, hypotension, heart rate of 130 beats/min and no respiratory abnormalities. Cranial CT showed subarachnoid hemorrhage with left frontal hematoma, cerebral edema and intracranial hypertension. She was classified as grade 4 on the Fisher scale for subarachnoid hemorrhage and underwent an external ventricular derivation surgery. On hospitalization day 4, the patient developed pneumonia. The chest radiograph showed opacity in the right lower lobe of the lung. Intravenous piperacillin/tazobactam 0.5 g plus4 g/6 h and IV linezolid 600 mg/12 h were administered for 7 and 10 days respectively, to treat the nosocomial pneumonia. After hospitalization day 16, fever developed (38.8 °C). Because her clinical condition worsened, IV polymyxin E 150 mg/12 h for 7 days and IV meropenem 1 g/8 h for 9 days were initiated. Intrathecal polymyxin E (5 mg/day for 3 days, followed by its use on every other day to complete 14 days of treatment) was administered because fever and GCS score of 3/15 persisted. This medication was introduced based on CSF results on day 18 ( Table 2 ). CSF analysis showed pleocytosis with neutrophil predominance and K. pneumoniae grew on culturing. Antimicrobial susceptibility testing showed sensitivity to amikacin, gentamicin and polymyxin B (MIC=0.5 µg/mL) and resistance to all β-lactam antibiotics. K. pneumoniae harbored bla- CTX-M, bla- SHV, and bla- KPC genes. The strain belonged to clone ST 2687 in MLST. Due to favorable clinical and laboratory results, after hospitalization day 46, the patient was transferred to a hospital in Sao Gabriel do Oeste, MS, so that we do not have further information about her.

Table 2
Case 2 cerebrospinal fluid characteristics compatible with an acute bacterial meningitis caused by a KPC-producing K. pneumoniae.

DISCUSSION

Nosocomial bacterial meningitis, especially carbapenem-resistant intracranial bacterial infections, are life-threatening complications in neurosurgical patients1111. Khan SA, Wagas M, Siddiqui UT, Shamim MS, Nathani KR, Jooma R, et al. Intrathecal and intraventricular antibiotics for postoperative Gram-negative meningitis and ventriculitis. Surg Neurol Int. 2017;8:226. , 1212. Bardak-Ozcem S, Sipahi OR. An updated approach to healthcare-associated meningitis. Expert Rev Anti Infect Ther. 2014;12:333-42. . The most frequent causative agents of health-care-associated meningitis are Staphylococcus spp. and multidrug-resistant and extensively drug-resistant gram-negative bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and K. pneumoniae 1313. Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Scheld WM, et al. 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64:e34-e65. . K. pneumoniae causes several nosocomial infections. The most common sites of CRKP infection are the respiratory system, urinary tract and bloodstream. CRKP is rarely isolated from CSF samples44. Almeida SM, Nogueira KS, Palmeiro JK, Scheffer MC, Stier CJ, França JC, et al. Nosocomial meningitis caused by Klebsiella pneumonia producing carbapenemase, with initial cerebrospinal fluid minimal inflammatory response. Arq Neuropsiquiat. 2014;72:398-9. , 55. Holyk A, Belden V, Lee JJ, Musick W, Keul R, Britz GW, et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Antimicrob Chemother. 2018;73:254-6. , 1414. Yang KC, Shrestha T, Kolakshyapati M, Shi LF, Wang Z, Li M, et al. Occult community acquired Klebsiella pneumoniae purulent meningitis in an adult: a case report. Medicine (Baltimore). 2018;97:e11017. .

Meningitis caused by CRKP post-neurosurgery has been reported in many countries, including Turkey1515. Mermer S, Aydemir S, Ozgiray E, Sipahi OR. Carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Chemother. 2016;28:454-5. , USA55. Holyk A, Belden V, Lee JJ, Musick W, Keul R, Britz GW, et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Antimicrob Chemother. 2018;73:254-6. and China1616. Chen Y, Liu L. The treatment of nosocomial meningitis and brain abscess by carbapenem-resistant Klebsiella pneumoniae. Br J Neurosurg. In press 2019. . In Brazil, Tuon et al .1717. Tuon FF, Rocha JL, Arend LN, Wallbach K, Zanin HA, Pilonetto M. Treatment and outcome of nine cases of KPC-producing Klebsiella pneumoniae meningitis. J Infect. 2013;67:161-4. described for the first time a nosocomial KPC-producing K. pneumoniae meningitis in the South region. To our knowledge, these are the first CRKP meningitis cases described in the Midwest of Brazil. Invasive procedures, including mechanical ventilation and central venous catheterization are associated with the acquisition of multi-resistant bacteria. Surgery is a risk factor for CRKP infections1616. Chen Y, Liu L. The treatment of nosocomial meningitis and brain abscess by carbapenem-resistant Klebsiella pneumoniae. Br J Neurosurg. In press 2019. . Infections after head trauma, similar to our cases, followed by neurosurgical procedures and gram-negative meningitis/ventriculitis, have been reported1111. Khan SA, Wagas M, Siddiqui UT, Shamim MS, Nathani KR, Jooma R, et al. Intrathecal and intraventricular antibiotics for postoperative Gram-negative meningitis and ventriculitis. Surg Neurol Int. 2017;8:226. .

Diagnosis of meningitis can be difficult. CSF cultures are the most important test to diagnose healthcare-associated ventriculitis and meningitis1313. Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Scheld WM, et al. 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64:e34-e65. . Although bacteriological CSF cultures from Case 1 on day 11 indicated CRKP and CSF parameters were consistent with meningitis, lymphocytosis was initially present. Lymphocytosis may be present as a component of acute bacterial meningitis mainly in neonatal and pediatric patients1818. Akturk H, Sutcu M, Somer A, Aydın D, Cihan R, Ozdemir A, et al. Carbapenem-resistant Klebsiella pneumoniae colonization in pediatric and neonatal intensive care units: risk factors for progression to infection. Braz J Infect Dis. 2016;20:134-40. , 1919. Powers WJ. Cerebrospinal fluid lymphocytosis in acute bacterial meningitis. Am J Med. 1985;79:216-20. . The emergence of CRKP infections is a rising public health threat associated with extremely high morbidity and mortality rates that demand caution with antibiotic use1212. Bardak-Ozcem S, Sipahi OR. An updated approach to healthcare-associated meningitis. Expert Rev Anti Infect Ther. 2014;12:333-42. , 1616. Chen Y, Liu L. The treatment of nosocomial meningitis and brain abscess by carbapenem-resistant Klebsiella pneumoniae. Br J Neurosurg. In press 2019. .

In our two cases, we observed K. pneumoniae isolates co-producing extended-spectrum β-lactamases (ESBLs) and KPC enzymes. ESBLs of TEM, SHV and CTX-M types are very common among Klebsiella spp99. Oliveira CF, Dal Forno NL, Alves IA, Horta JA, Rieger A, Alves SH. Prevalence of the TEM, SHV and CTX-M families of extended-spectrum [beta]-lactamases in Escherichia coli and Klebsiella spp at the University Hospital of Santa Maria, State of Rio Grande do Sul. Rev Soc Bras Med Trop. 2009;42:556-60. . ESBL-producing K. pneumoniae may be more invasive and resistant and the distribution of these bacteria varies according to geographical areas2020. Sahly H, Aucken H, Benedí VJ, Forestier C, Fussing V, Hansen DS, et al. Increased serum resistance in Klebsiella pneumoniae strains producing extended-spectrum β-lactamases. Antimicrob Agents Chemother. 2004;48:3477-82. . CRKP is already endemic in many countries, including Brazil. This mechanism confers a high resistance to β-lactams, including carbapenems33. Tängdén T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. J Intern Med. 2015;277:501-12. , 2020. Sahly H, Aucken H, Benedí VJ, Forestier C, Fussing V, Hansen DS, et al. Increased serum resistance in Klebsiella pneumoniae strains producing extended-spectrum β-lactamases. Antimicrob Agents Chemother. 2004;48:3477-82. . A study conducted in Mato Grosso do Sul State reported a high rate (93.3%) of CRKP in that region2121. Campos CC, Roriz NF, Espínola CN, Lopes FA, Tieppo C, Tetila AF, et al. KPC: an important mechanism of resistance in K. pneumoniae isolates from intensive care units in the Midwest region of Brazil. J Infect Dev Ctries. 2017;11:646-51. . Genetic polymorphism analyses of the two K. pneumoniae isolates revealed two different clones: ST1298 and ST2687. In Brazil, sequence types ST11, ST437, and ST340 are more frequently reported among K. pneumoniae isolates, while ST258 are the most frequently associated with KPC enzyme production in Europe and the USA2222. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016;7:895. . Here, we report for the first time the involvement of ST1298 and ST2687 in meningitis caused by CRKP. Treatment of central nervous system infections is more limited than those of bloodstream and pulmonary infections. There are limited data on optimal dosing and brain barrier penetration of most agents administered to treat carbapenem-resistant Enterobacteriaceae infections66. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: 22thinformational supplement (M100-S27). Wayne: CLSI; 2017. , 2323. Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daiko GL, Forrest A, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39:10-39. .

CRKP infections are treated with combination therapies, including polymyxin or tigecycline with carbapenems, aminoglycosides, fluoroquinolones or fosfomycin2222. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016;7:895. . A high carbapenem MIC (MIC ≥8µg/mL) predicts a lower response to the antibiotic2323. Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daiko GL, Forrest A, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39:10-39. . The relatively new antimicrobial ceftazidime-avibactam (approved in 2014 by the U.S. Food and Drug Administration, USA) has been successfully used for treating CRKP meningitis. The drug is less toxic and can inhibit KPC-2 carbapenemase and group C beta-lactamases55. Holyk A, Belden V, Lee JJ, Musick W, Keul R, Britz GW, et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Antimicrob Chemother. 2018;73:254-6. . Ceftazidime-avibactam has a great treatment potential because of its direct action on the carbapenem resistance mechanism. However, this option was not available for the reported cases. Although intravenous polymyxins poorly penetrate the CSF and they present with high pharmacokinetic variability, the combination of intravenous polymyxin E and intrathecal polymyxin showed satisfactory responses with resolution of meningitis2323. Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daiko GL, Forrest A, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39:10-39. .

We reported two rare cases of meningitis caused by CRKP that were satisfactorily treated with intravenous polymyxin and intrathecal polymyxin, despite the associated high mortality reported in literature.

ACKNOWLEDGMENTS

We thank the team of the Microbiology laboratories of the Hospitals for providing the studied K. pneumoniae strains. We thank the team of LAPIH/IOC/FIOCRUZ for their colaboration for the molecular tests.

REFERENCES

  • 1
    Hasbun R, Rosenthal N, Balada-Llasat JM, Chung J, Duff S, Bozzette S, et al. Epidemiology of meningitis and encephalitis in the United States, 2011–2014. Clin Infect Dis. 2017;65:359-63.
  • 2
    Pereira PS, Araujo CF, Seki LM, Zahner V, Carvalho-Assef AP, Asensi MD. Update of the molecular epidemiology of KPC-2-producing Klebsiella pneumoniae in Brazil: spread of clonal complex 11 (ST11, ST437 and ST340). J Antimicrob Chemother. 2012;68:312-6.
  • 3
    Tängdén T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. J Intern Med. 2015;277:501-12.
  • 4
    Almeida SM, Nogueira KS, Palmeiro JK, Scheffer MC, Stier CJ, França JC, et al. Nosocomial meningitis caused by Klebsiella pneumonia producing carbapenemase, with initial cerebrospinal fluid minimal inflammatory response. Arq Neuropsiquiat. 2014;72:398-9.
  • 5
    Holyk A, Belden V, Lee JJ, Musick W, Keul R, Britz GW, et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Antimicrob Chemother. 2018;73:254-6.
  • 6
    Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: 22thinformational supplement (M100-S27). Wayne: CLSI; 2017.
  • 7
    Monteiro J, Widen RH, Pignatari AC, Kubasek C, Silbert S. Rapid detection of carbapenemase genes by multiplex real-time PCR. J Antimicrob Chemother. 2012;67:906-9.
  • 8
    Senda K, Arakawa Y, Ichiyama S, Nakashima K, Ito H, Ohsuka S, et al. PCR detection of metallo-beta-lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum beta-lactams. J Clin Microbiol. 1996;34:2909-13.
  • 9
    Oliveira CF, Dal Forno NL, Alves IA, Horta JA, Rieger A, Alves SH. Prevalence of the TEM, SHV and CTX-M families of extended-spectrum [beta]-lactamases in Escherichia coli and Klebsiella spp at the University Hospital of Santa Maria, State of Rio Grande do Sul. Rev Soc Bras Med Trop. 2009;42:556-60.
  • 10
    Diancourt L, Passet V, Verhoef J, Grimont PA, Brisse S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol. 2005;43:4178-82.
  • 11
    Khan SA, Wagas M, Siddiqui UT, Shamim MS, Nathani KR, Jooma R, et al. Intrathecal and intraventricular antibiotics for postoperative Gram-negative meningitis and ventriculitis. Surg Neurol Int. 2017;8:226.
  • 12
    Bardak-Ozcem S, Sipahi OR. An updated approach to healthcare-associated meningitis. Expert Rev Anti Infect Ther. 2014;12:333-42.
  • 13
    Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Scheld WM, et al. 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017;64:e34-e65.
  • 14
    Yang KC, Shrestha T, Kolakshyapati M, Shi LF, Wang Z, Li M, et al. Occult community acquired Klebsiella pneumoniae purulent meningitis in an adult: a case report. Medicine (Baltimore). 2018;97:e11017.
  • 15
    Mermer S, Aydemir S, Ozgiray E, Sipahi OR. Carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Chemother. 2016;28:454-5.
  • 16
    Chen Y, Liu L. The treatment of nosocomial meningitis and brain abscess by carbapenem-resistant Klebsiella pneumoniae. Br J Neurosurg. In press 2019.
  • 17
    Tuon FF, Rocha JL, Arend LN, Wallbach K, Zanin HA, Pilonetto M. Treatment and outcome of nine cases of KPC-producing Klebsiella pneumoniae meningitis. J Infect. 2013;67:161-4.
  • 18
    Akturk H, Sutcu M, Somer A, Aydın D, Cihan R, Ozdemir A, et al. Carbapenem-resistant Klebsiella pneumoniae colonization in pediatric and neonatal intensive care units: risk factors for progression to infection. Braz J Infect Dis. 2016;20:134-40.
  • 19
    Powers WJ. Cerebrospinal fluid lymphocytosis in acute bacterial meningitis. Am J Med. 1985;79:216-20.
  • 20
    Sahly H, Aucken H, Benedí VJ, Forestier C, Fussing V, Hansen DS, et al. Increased serum resistance in Klebsiella pneumoniae strains producing extended-spectrum β-lactamases. Antimicrob Agents Chemother. 2004;48:3477-82.
  • 21
    Campos CC, Roriz NF, Espínola CN, Lopes FA, Tieppo C, Tetila AF, et al. KPC: an important mechanism of resistance in K. pneumoniae isolates from intensive care units in the Midwest region of Brazil. J Infect Dev Ctries. 2017;11:646-51.
  • 22
    Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016;7:895.
  • 23
    Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daiko GL, Forrest A, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39:10-39.

  • ETHICAL APPROVAL
    This study was approved by the ethics committee (CAAE - 50087815.2.0000.0021).

  • FUNDING
    This study was financed in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Instituto Oswaldo Cruz (IOC) of Fundação Oswaldo Cruz and Universidade Federal de Mato Grosso do Sul.

Publication Dates

  • Publication in this collection
    20 Dec 2019
  • Date of issue
    2019

History

  • Received
    2 July 2019
  • Accepted
    30 Oct 2019
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