Skip to main content
SpringerLink
Log in

Continuous infusion of ceftolozane-tazobactam resulted in high cerebrospinal fluid concentrations of ceftolozane in a patient with multidrug-resistant Pseudomonas aeruginosa meningitis

  • Case Report
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Multidrug-resistant Pseudomonas aeruginosa has limited treatment options. Treatment of healthcare-associated meningitis requires agents active against the organism in vitro and able to penetrate the cerebrospinal fluid adequately. Ceftolozane-tazobactam has been recently approved to treat various Gram-negative organisms, including Pseudomonas aeruginosa; however, ceftolozane’s penetration into human cerebrospinal fluid is unknown. Here, we present a case of a patient with multidrug-resistant Pseudomonas aeruginosa meningitis treated with a continuous infusion of ceftolozane-tazobactam. Samples of both serum and cerebrospinal fluid were analyzed for ceftolozane concentration on continuous infusion. Cerebrospinal fluid concentrations of ceftolozane were 83% of that in serum. Treatment with ceftolozane-tazobactam, along with combinations of other antibiotics, resulted in clearance of organism from the patient’s cerebrospinal fluid and marked decrease in inflammatory cells. Studies are warranted to determine the efficacy of ceftolozane-tazobactam for patients with healthcare-associated meningitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. US Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States, 2013. CDC. 2013. https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf. Accessed 29 Aug 2019.

  2. Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect Control Hosp Epidemiol. 2016;37:1288–301.

    Article  Google Scholar 

  3. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268–81.

    Article  CAS  Google Scholar 

  4. Zerbaxa [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2019.

  5. Ramanan M, Lipman J, Shorr A, Shankar A. A meta-analysis of ventriculostomy-associated cerebrospinal fluid infections. BMC Infect Dis. 2015;14:1–12.

    Google Scholar 

  6. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 29th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2019.

  7. Dinh A, Wyplosz B, Kernéis S, Lebeaux D, Bouchand F, Duran C, et al. Use of ceftolozane/tazobactam as salvage therapy for infections due to extensively drug-resistant Pseudomonas aeruginosa. Int J Antimicrob Agents. 2017;49:782–3.

    Article  CAS  Google Scholar 

  8. Frattari A, Savini V, Polilli E, Cibelli D, Talamazzi S, Bosco D, et al. Ceftolozane-tazobactam and Fosfomycin for rescue treatment of otogenous meningitis caused by XDR Pseudomonas aeruginosa: Case report and review of the literature. IDCases. 2018;14:e00451.

    Article  Google Scholar 

  9. Albanèse J, Léone M, Bruguerolle B, Ayem ML, Lacarelle B, Martin C. Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit. Antimicrob Agents Chemother. 2000;44:1356–8.

    Article  Google Scholar 

  10. Huang H, Huang S, Zhu P, Xi X. Continuous versus intermittent infusion of cefepime in neurosurgical patients with post-operative intracranial infections. Int J Antimicrob Agents. 2014;43:68–72.

    Article  CAS  Google Scholar 

  11. Pilmis B, Petitjean G, Lesprit P, Lafaurie M, El Helali N, Le Monnier A, et al. Continuous infusion of ceftolozane/tazobactam is associated with a higher probability of target attainment in patients infected with Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis. 2019;38:1457–61.

    Article  CAS  Google Scholar 

  12. Tam VH. Pharmacodynamics of cefepime in patients with Gram-negative infections. J Antimicrob Chemother. 2002;50:425–8.

    Article  CAS  Google Scholar 

  13. Aitken SL, Altshuler J, Guervil DJ, Hirsch EB, Ostrosky-Zeichner LL, Ericsson CD, et al. Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia. Int J Antimicrob Agents. 2015;45:541–4.

    Article  CAS  Google Scholar 

  14. Li C, Du X, Kuti JL, Nicolau DP. Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections. Antimicrob Agents Chemother. 2007;51:1725–30.

    Article  CAS  Google Scholar 

  15. Tam VH, Schilling AN, Neshat S, Poole K, Melnick DA, Coyle EA. Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005;49:4920–7.

    Article  CAS  Google Scholar 

  16. Lee SY, Kuti JL, Nicolau DP. Cefepime pharmacodynamics in patients with extended spectrum β-lactamase (ESBL) and non-ESBL infections. J Infect. 2007;54:463–8.

    Article  Google Scholar 

  17. Nau R, Kinzig-Schippers M, Sörgel F, Schinschke S, Rössing R, Müller C, et al. Kinetics of piperacillin and tazobactam in ventricular cerebrospinal fluid of hydrocephalic patients. Antimicrob Agents Chemother. 1997;41:987–91.

    Article  CAS  Google Scholar 

  18. Frank U, Mutter J, Schmidt-Eisenlohr E, Daschner FD. Comparative in vitro activity of piperacillin, piperacillin-sulbactam and piperacillin-tazobactam against nosocomial pathogens isolated from intensive care patients. Clin Microbiol Infect. 2003;9:1128–32.

    Article  CAS  Google Scholar 

  19. Kuo HY, Der WF, Yen YF, Lin ML, Liu CY. In vitro activities of piperacillin or cefoperazone alone and in combination with β-lactamase inhibitors against Gram-negative bacilli. New Microbiol. 2009;32:49–55.

    CAS  PubMed  Google Scholar 

  20. Strayer AH, Gilbert DH, Pivarnik P, Medeiros AA, Zinner SH, Dudley MN. Pharmacodynamics of piperacillin alone and in combination with tazobactam against piperacillin-resistant and -susceptible organisms in an in vitro model of infection. Antimicrob Agents Chemother. 1994;38:2351–6.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, Loma Linda University Medical Center, 11223 Campus Street, Loma Linda, CA, 92354, USA

    S. Alexander Winans & Steven C. Forland

  2. Loma Linda University School of Medicine, Loma Linda, CA, USA

    Richelle L. Guerrero-Wooley & Steven C. Forland

  3. Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, CA, USA

    Susie H. Park, Garret Hino Jr. & Steven C. Forland

Authors
  1. S. Alexander Winans
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richelle L. Guerrero-Wooley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susie H. Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Garret Hino Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Steven C. Forland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Alexander Winans.

Ethics declarations

Conflict of interest

The authors have declared no conflicts of interest for this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Winans, S.A., Guerrero-Wooley, R.L., Park, S.H. et al. Continuous infusion of ceftolozane-tazobactam resulted in high cerebrospinal fluid concentrations of ceftolozane in a patient with multidrug-resistant Pseudomonas aeruginosa meningitis. Infection 49, 355–359 (2021). https://doi.org/10.1007/s15010-020-01510-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-020-01510-8

Keywords

Search

Navigation