Clinical Infectious Diseases Advance Access published May 28, 2015
1
Ceftolozane/tazobactam Therapy of Respiratory Infections Due to Multi-Drug Resistant
cr ipt
Pseudomonas aeruginosa
Michael S. Gelfand, Kerry O. Cleveland
Division of Infectious Diseases, Department of Medicine, University of Tennessee Health
an
Correspondence: 1325 Eastmoreland Avenue, Suite 460, Memphis, TN 38104, Phone: +1(901)448-5770, Fax: +1(901)448-5940, [email protected]
Ac
ce
pt ed
M
Alternate corresponding author: Michael S. Gelfand, M.D. [email protected]
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
Science Center, Memphis, Tennessee, USA
2
To the Editor –
cr ipt
Ceftolozane-tazobactam (CT) has recently been approved in the United States for the treatment of complicated urinary tract infections and, in conjunction with metronidazole, for
intra-abdominal infections [1]. The in vitro spectrum of CT’s activity includes both susceptible and multi-drug resistant (MDR) strains of Pseudomonas aeruginosa (PA). Farrell et al have
With increasing resistance of PA isolates to antimicrobial agents such as beta-lactams
an
and fluoroquinolones as well as an aging population with increased risk of nephrotoxicity from other anti-PA drugs such as aminoglycosides and polymyxins, CT offers an attractive option in
M
the management of infections due to MDR PA.
PA is a common cause of healthcare-associated pneumonia and ventilator-associated
pt ed
pneumonia [3]. We recently successfully used CT in the treatment of three patients with pneumonia due to MDR PA. All patients were diagnosed using conventional criteria of fever, new pulmonary infiltrate on imaging, leukocytosis, and growth of PA in a culture of respiratory secretions. No patient was bacteremic. We dosed CT at 3 grams intravenously every 8 hours as
ce
is currently being studied in a clinical trial for ventilator-associated pneumonia [4]. Details of the three cases are summarized in Table 1.
Ac
The choice of effective therapy for serious Gram-negative infections is currently
complicated by recurrent shortages of antibiotics. For example, supply shortages of piperacillin/tazobactam has led to, in our experience, an increased use of carbapenems. This raises a serious concern of stimulating the more rapid emergence of carbapenem-resistant organisms. All three isolates from our patients demonstrated in vitro resistance to
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
reported that CT is the most active commercially available anti-PA beta-lactam antibiotic [2].
3
meropenem. Additionally, CT offers an alternative to carbapenems when extended-spectrum beta-lactamase producing organisms are suspected or documented [5, 6].
cr ipt
While CT is not currently FDA-approved for the treatment of pneumonia, increasing antimicrobial resistance among Gram-negative organisms makes selection of therapy
progressively difficult. Pending further information from ongoing clinical trials, we wanted to
Funding
Acknowledgments
an
No funding was received for this work.
Ac
ce
pt ed
M
Both MSG and KOC have served on the speakers’ bureau for Cubist Pharmaceuticals.
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
share our experience with this new agent for an “off-label” indication.
4
References
Pharmaceuticals US; Revised December, 2014.
cr ipt
1. ZERBAXA (ceftolozane/tazobactam) [package insert]. Lexington, MA; Cubist
2. Farrell DJ, Sader HS, Flamm RK, Jones RN. Ceftolozane/tazobactam activity tested
against Gram-negative bacterial isolates from hospitalized patients with pneumonia in
3. Kollef MH, Chastre J, Fagon JY, et al. Global prospective epidemiologic and surveillance
Med 2014;42:2178-87.
an
study of ventilator-associated pneumonia due to Pseudomonas aeruginosa. Crit Care
M
4. Safety and efficacy study of ceftolozane/tazobactam to treat ventilated nosocomial pneumonia (ASPECT-NP). Available at:
https://clinicaltrials.gov/ct2/show/NCT02070757. Accessed 11 May 2015.
pt ed
5. Perez F, Bonomo RA. Bloodstream infection caused by extended spectrum β-lactamaseproducing Gram-negative bacteria: how to define the best treatment regimen? Clin Infect Dis 2015;60:1326-9.
ce
6. Solomkin J, Hershberger E, Miller B, et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results
Ac
from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin Infect Dis 2015;60:1462-71.
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
US and European medical centres (2012). Int J Antimicrob Agents 2014;43:533-9.
Clinical outcome
Ciprofloxacin
14 days
Cure
Meropenem Ciprofloxacin
14 days
CT = ceftolozane/tazobactam
Microbiologic outcome
sc
Duration of treatment with CT
Eradication
M an u
Prior antibiotic therapy
Cure
Meropenem Linezolid
10 days
Cure
Significant co-morbid conditions
Esophageal cancer Tracheostomy for respiratory failure
Eradication
Polyneuropathy Chronic corticosteroid use History of cardiopulmonary arrest Tracheostomy for respiratory failure
Eradication
AIDS (absolute CD4 count of 59 cells/mm3) Clostridium difficile-associated diarrhea with colon perforation and intra-abdominal abscess Respiratory failure
ed ep t
Susceptibilities [Drug (minimal inhibitory concentration in micrograms/milliliter)] 69 CT (0.25) years, Meropenem (>8) male Cefepime (8) Ciprofloxacin (>2) Piperacillin/tazobactam (16) Ciprofloxacin (>2) Piperacillin/tazobactam (>64) Tobramycin (>8) Colistin (susceptible) Polymyxin (susceptible) 52 CT (1) years, Meropenem (>8) male Cefepime (16) Ciprofloxacin (16) Tobramycin (
1
Ceftolozane/tazobactam Therapy of Respiratory Infections Due to Multi-Drug Resistant
cr ipt
Pseudomonas aeruginosa
Michael S. Gelfand, Kerry O. Cleveland
Division of Infectious Diseases, Department of Medicine, University of Tennessee Health
an
Correspondence: 1325 Eastmoreland Avenue, Suite 460, Memphis, TN 38104, Phone: +1(901)448-5770, Fax: +1(901)448-5940, [email protected]
Ac
ce
pt ed
M
Alternate corresponding author: Michael S. Gelfand, M.D. [email protected]
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
Science Center, Memphis, Tennessee, USA
2
To the Editor –
cr ipt
Ceftolozane-tazobactam (CT) has recently been approved in the United States for the treatment of complicated urinary tract infections and, in conjunction with metronidazole, for
intra-abdominal infections [1]. The in vitro spectrum of CT’s activity includes both susceptible and multi-drug resistant (MDR) strains of Pseudomonas aeruginosa (PA). Farrell et al have
With increasing resistance of PA isolates to antimicrobial agents such as beta-lactams
an
and fluoroquinolones as well as an aging population with increased risk of nephrotoxicity from other anti-PA drugs such as aminoglycosides and polymyxins, CT offers an attractive option in
M
the management of infections due to MDR PA.
PA is a common cause of healthcare-associated pneumonia and ventilator-associated
pt ed
pneumonia [3]. We recently successfully used CT in the treatment of three patients with pneumonia due to MDR PA. All patients were diagnosed using conventional criteria of fever, new pulmonary infiltrate on imaging, leukocytosis, and growth of PA in a culture of respiratory secretions. No patient was bacteremic. We dosed CT at 3 grams intravenously every 8 hours as
ce
is currently being studied in a clinical trial for ventilator-associated pneumonia [4]. Details of the three cases are summarized in Table 1.
Ac
The choice of effective therapy for serious Gram-negative infections is currently
complicated by recurrent shortages of antibiotics. For example, supply shortages of piperacillin/tazobactam has led to, in our experience, an increased use of carbapenems. This raises a serious concern of stimulating the more rapid emergence of carbapenem-resistant organisms. All three isolates from our patients demonstrated in vitro resistance to
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
reported that CT is the most active commercially available anti-PA beta-lactam antibiotic [2].
3
meropenem. Additionally, CT offers an alternative to carbapenems when extended-spectrum beta-lactamase producing organisms are suspected or documented [5, 6].
cr ipt
While CT is not currently FDA-approved for the treatment of pneumonia, increasing antimicrobial resistance among Gram-negative organisms makes selection of therapy
progressively difficult. Pending further information from ongoing clinical trials, we wanted to
Funding
Acknowledgments
an
No funding was received for this work.
Ac
ce
pt ed
M
Both MSG and KOC have served on the speakers’ bureau for Cubist Pharmaceuticals.
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
share our experience with this new agent for an “off-label” indication.
4
References
Pharmaceuticals US; Revised December, 2014.
cr ipt
1. ZERBAXA (ceftolozane/tazobactam) [package insert]. Lexington, MA; Cubist
2. Farrell DJ, Sader HS, Flamm RK, Jones RN. Ceftolozane/tazobactam activity tested
against Gram-negative bacterial isolates from hospitalized patients with pneumonia in
3. Kollef MH, Chastre J, Fagon JY, et al. Global prospective epidemiologic and surveillance
Med 2014;42:2178-87.
an
study of ventilator-associated pneumonia due to Pseudomonas aeruginosa. Crit Care
M
4. Safety and efficacy study of ceftolozane/tazobactam to treat ventilated nosocomial pneumonia (ASPECT-NP). Available at:
https://clinicaltrials.gov/ct2/show/NCT02070757. Accessed 11 May 2015.
pt ed
5. Perez F, Bonomo RA. Bloodstream infection caused by extended spectrum β-lactamaseproducing Gram-negative bacteria: how to define the best treatment regimen? Clin Infect Dis 2015;60:1326-9.
ce
6. Solomkin J, Hershberger E, Miller B, et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results
Ac
from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin Infect Dis 2015;60:1462-71.
Downloaded from http://cid.oxfordjournals.org/ at New York University on June 5, 2015
us
US and European medical centres (2012). Int J Antimicrob Agents 2014;43:533-9.
Clinical outcome
Ciprofloxacin
14 days
Cure
Meropenem Ciprofloxacin
14 days
CT = ceftolozane/tazobactam
Microbiologic outcome
sc
Duration of treatment with CT
Eradication
M an u
Prior antibiotic therapy
Cure
Meropenem Linezolid
10 days
Cure
Significant co-morbid conditions
Esophageal cancer Tracheostomy for respiratory failure
Eradication
Polyneuropathy Chronic corticosteroid use History of cardiopulmonary arrest Tracheostomy for respiratory failure
Eradication
AIDS (absolute CD4 count of 59 cells/mm3) Clostridium difficile-associated diarrhea with colon perforation and intra-abdominal abscess Respiratory failure
ed ep t
Susceptibilities [Drug (minimal inhibitory concentration in micrograms/milliliter)] 69 CT (0.25) years, Meropenem (>8) male Cefepime (8) Ciprofloxacin (>2) Piperacillin/tazobactam (16) Ciprofloxacin (>2) Piperacillin/tazobactam (>64) Tobramycin (>8) Colistin (susceptible) Polymyxin (susceptible) 52 CT (1) years, Meropenem (>8) male Cefepime (16) Ciprofloxacin (16) Tobramycin (
