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Inicio Gastroenterología y Hepatología (English Edition) Ertapenem failure as therapy for nosocomial spontaneous bacterial peritonitis
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Vol. 39. Issue 10.
Pages 663-665 (December 2016)
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Vol. 39. Issue 10.
Pages 663-665 (December 2016)
Scientific letter
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Ertapenem failure as therapy for nosocomial spontaneous bacterial peritonitis
FALLO DE ERTAPENEM EN EL TRATAMIENTO DE LA PERITONITIS BACTERIANA ESPONTÁNEA NOSOCOMIAL
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José Castellotea,
Corresponding author
, Alba Cacheroa, Anna Girbaua, Eva Dueñasa, Inmaculada Graub
a Unidad de Hepatología y Trasplante hepático, IDIBELL, Hospital Univeristari de Bellvitge, L’Hospitalet de LLobregat, Barcelona, Spain
b Servicio de Enfermedades Infecciosas, IDIBELL, Hospital Univeristari de Bellvitge, L’Hospitalet de LLobregat, Barcelona, Spain
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Table 1. Asctic fluid, blood culture and polymorphonuclear count and antibiotic therapy in the three cases.
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Nosocomial spontaneous bacterial peritonitis (SBP) accounts for one third of all SBP episodes and is caused by microorganisms resistant to third generation cephalosporins (3rdGC) up to 40% of cases, mainly due to extended-spectrum β-lactamases (ESBL) Escherichia coli and Klebsiella pneumoniae producing strains, other Enterobacteriaceae spp. and some gram positive bacteria.1 In this setting, 3rdGC must not be used as empirical antibiotic therapy in nosocomial SBP. Carbapenems have been recommended based in bacteriological data reported in these cases.2,3 Ertapenem, a parenteral broad-spectrum 1-beta-methyl carbapenem was approved by FDA in US and in Europe for complicated intra-abdominal infections. We are treating nosocomial SBP with ertapenem provided that 93% of isolated bacteria in nosocomial SBP of our center were sensible in vitro to this carbapenem. We report three cases of nosocomial SBP caused by ertapenem-susceptible, ESBL-producing E. coli and K. pneumoniae with a microbiological and clinical failure to recommended standard doses of 1g/24h.

Case 1

A 62-year-old male cirrhotic patient was admitted because of refractory ascites and hepato-renal syndrome (HRS). He presented with anasarca and a MELD score of 24. After HRS recovery, he developed hepatic encephalopathy and fever with a creatinine of 66μmol/L, albumin of 22g/L and bilirubin of 121μkat/L. He was receiving prophylaxis with norfloxacin. Ertapenem 1g every 24h was initiated. An ESBL-producing K. pneumoniae was isolated in ascitic fluid culture with a MIC<0.5mg/L for ertapenem, however after 48h ascitic fluid (AF) PMN count was higher and culture was still positive. After changing therapy to meropenem 500mg/8h, the AF culture become negative and PMN count normalized.

Case 2

A 41-year-old female patient was admitted for fever and ascites 9 months after orthotopic liver transplantation. Creatinine was 110μmol/L, albumin 36g/L and bilirubin 12μkat/L. She was immunosuppressed with tacrolimus. Ertapenem 1g/24h was begun. AF culture yielded an ESBL-producing K. pneumonia with a MIC <0.5mg/L. During the following days, PMN count decreased but ascitic fluid culture remained positive. After 6 days, although the patient improved clinically, we changed antibiotic therapy to imipenem 500mg/6h and AF culture became negative after 24h of therapy.

Case 3

A 65-year-old male was admitted due to acute variceal bleeding. Patient was treated following our standard protocol. He developed a hepato-renal syndrome and was treated with terlypressin and albumin. Creatinine was 152μmol/L, albumin 29g/L and bilirubin 121μkat/L. AF analysis was diagnostic of SBP and ascitic and blood culture grew ESBL-E. coli with a MIC<0.5mg/L for ertapenem. In the following days, patient improved and the PMN count in ascitic fluid decreased; however AF culture remained positive until day 6 of therapy. We stopped antibiotic therapy at day 13 with normal PMN count and ascitic fluid culture finally negative. A summary of all AF analysis and cultures are shown in Table 1.

Table 1.

Asctic fluid, blood culture and polymorphonuclear count and antibiotic therapy in the three cases.

Case 1  Day 0  Day 2  Day 3  Day 7 
AF* PMN&  200/μL  600/μL    200/μL 
AF* culture  Klebsiella pneumoniae-ESBL  Klebsiella pneumoniae-ESBL    Negative 
Blood culture  Negative  Not done    Not done 
Antibiotic therapy  Ertapenem 1g/24  Stop ertapenem. Meropenem 500mg/8Meropenem 500mg/8
Case 2  Day 0  Day 2  Day 6  Day 7 
AF* PMN&  5478/μL  1496/μL  525/μL  200/μL 
AF culture  Klebsiella pneumoniae-ESBL  Klebsiella pneumoniae-ESBL  Klebsiella pneumoniae-ESBL  Negative 
Blood culture  Negative  Not done  Not done  Not done 
Antibiotic therapy  Ertapenem 1g/24  Stop ertapenem. Imipenem 500mg/6Imipenem 500mg/6
Case 3  Day 0  Day 2  Day 4  Day 6  Day 9  Day 13 
AF* PMN&  7221/μL  4590/μL  2960/μL  560/μL  330/μL  <100/μL 
AF* culture  Escherichia coli-ESBL  Escherichia coli-ESBL  Escherichia coli-ESBL  Escherichia coli-ESBL  Negative  Negative 
Blood culture  Escherichia coli-ESBL  Not done  Not done  Not done  Not done  Not done 
Antibiotic therapy  Ertapenem 1g/24        Stop ertapenem 
*

Ascitic fluid.

&

Polymorphonuclear count.

Carbapenems are considered the drugs of choice for serious infections due to ESBL-producing bacteria.4 Ertapenem is a good option when coverage against Pseudomonas aeruginosa or Acinetobacter baumannii is not needed,5 and it is recommended for the treatment of complicated intra-abdominal infections.6 It is noteworthy that despite a good sensibility in vitro measured by a MIC of <0.5mg/L, treatment failed to resolve infection in patient 1 and 2 and delayed SBP resolution in case 3. Verdier et al.7 studied ertapenem concentration in plasma and peritoneal fluid from patients with severe intra-abdominal infections. The study showed that ertapenem at 1 gr/day achieved highly variable plasma and peritoneal antibiotic concentrations. Ertapenem had a good peritoneal diffusion, but concentrations were frequently below the susceptibility breakpoint for ESLB-Enterobacteriaceae. Data in cirrhotic patients with ascites are not available. Host factors as hypoalbuminaemia may have a profound effect on ertapenem pharmacokinetics producing a decreased concentration in plasma and tissues.8 This may be relevant in cirrhotic patients. As others β-lactams, time above MIC is a key point to achieve good clinical and microbiological results and prevent resistance.

Resistance to ertapenem in ESBL-producing isolates during therapy may occur due to concurrent loss of porins and has been described in both K. penumoniae9 and E. coli.10 Nevertheless, in our three cases, MIC for ertapenem did not change during therapy in AF isolated bacteria.

Appropriate antibiotic empirical therapy in nosocomial SBP is unknown. Other carbapenem, imipenem and meropenem, and piperacillin–tazobactam alone or associated with glycopeptides have been suggested although randomized clinical trials are scanty.11 Knowing prevalence and susceptibility of bacteria involved in nosocomial SBP in each center is mandatory to choose the best option. Pharmacokinetic studies of new therapies are needed. In critically-ill cirrhotic patients, ertapenem at 1g/day may be insufficient due to hypoalbuminaemia and a low AF antibiotic concentration and 1 gr twice day may be more suitable for nosocomial SBP treatment.

References
[1]
X. Ariza, J. Castellote, J. Lora-Tamayo, A. Girbau, S. Salord, R. Rota, et al.
Risk factors for resistance to ceftriaxone and its impact on mortality in community, healthcare and nosocomial spontaneous bacterial peritonitis.
J Hepatol, 56 (2012), pp. 825-832
[2]
R. Wiest, A. Krag, A. Gerbes.
Spontaneous bacterial peritonitis: recent guidelines and beyond.
[3]
R. Jalan, J. Fernandez, R. Wiest, B. Schnabl, R. Moreau, P. Angeli, et al.
Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013.
J Hepatol, 60 (2014), pp. 1310-1324
[4]
M. Delgado-Valverde, J. Sojo-Dorado, A. Pascual, J. Rodriguez-Baño.
Clinical management of infections caused by multi-drug resistant Enterobacteriaceae.
Ther Adv Infect Dis, 1 (2013), pp. 49-69
[5]
V.L. Collins, D. Marchain, J.M. Poque, V. Moshos, S. Bheemreddy, B. Sunkara, et al.
Efficacy of ertapenem treatment of bloodstream infections caused by extended-spectrum-β-lactamase producing Enterobacteriaceae.
Antimicrob Agents Chemother, 56 (2012), pp. 2173-2177
[6]
J.S. Solomkin, J.E. Mazuski, J.S. Bradley, K.A. Rodvold, E.J. Goldstein, E.S. Baron, et al.
Diagnosis and management of complicated intra-abdominal infections in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.
Clin Infect Dis, 11 (2010), pp. 79-109
[7]
M.C. Verdier, P. Seguin, B. Le Touvet, A. Cady, Y. Mallédant, O. Tribut.
Ertapenem in plasma and peritoneal fluid from patients with severe intra-abdominal infections.
J Antimicrob Chemother, 66 (2011), pp. 1934-1936
[8]
M. Ulldemolins, J.A. Roberts, J. Rello, D.L. Paterson, J. Lipman.
The effects of hypoalbuminaemia and optimizing antibacterial dosing in critically ill patients.
Clin Pharmacokinet, 50 (2011), pp. 99-100
[9]
D. Skurnik, S. Lasocki, S. Bremont, C. Muller-Serieys, M. Kitzis, P. Courvalin, et al.
Development of ertapenem resistance in a patient with mediastinitis caused by Klebsiella pneumoniae producing an extended-spectrum beta-lactamase.
J Med Microbiol, 59 (2010), pp. 115-119
[10]
M. Lartigue, L. Poirel, C. Poyart, H. Reglier-Poupet, P. Nordmann.
Ertapenem resistance of Escherichia coli.
Emerg Infect Dis, 13 (2007), pp. 315-317
[11]
S. Piano, S. Fasolato, F. Salinas, A. Romano, M. Tonon, F. Morando, et al.
The empirical antibiotic treatment of nosocomial spontaneous bacterial peritonitis: results of a randomized controlled clinical trial.
Copyright © 2015. Elsevier España, S.L.U. and AEEH y AEG
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