Posts filed under ‘Infecciones intraabdominales’

Profile of ceftolozane/tazobactam and its potential in the treatment of complicated intra-abdominal infections.

Drug Des Devel Ther. 2015 Jun 4;9:2919-25.

Skalweit MJ1.

1Department of Medicine, Louis Stokes Cleveland Department of Veterans Affairs and Case Western Reserve University School of Medicine, Cleveland, OH, USA ; Department of Biochemistry, Louis Stokes Cleveland Department of Veterans Affairs and Case Western Reserve University School of Medicine, Cleveland, OH, USA.


Drug-resistant pathogens have gained a foothold especially in the most vulnerable patient populations, hospitalized and immunocompromised individuals.

Furthermore, extended-spectrum β-lactamase and carbapenemase-producing organisms are finding their way even into the community, with patients presenting to the hospital with established colonization and infection with resistant Enterobacteriaceae in particular.

Recently, a novel antipseudomonal cephalosporin in combination with an established Class A β-lactamase inhibitor, ceftolozane/tazobactam has been approved by the FDA for use in the treatment of complicated urinary tract infections and complicated intra-abdominal infections.

Ceftolozane is a uniquely potent antipseudomonal cephalosporin because of its high affinity for the penicillin-binding proteins of Pseudomonas aeruginosa, its low affinity for the intrinsic Class C β-lactamases of P. aeruginosa, its ability to enter P. aeruginosa through the outer membrane without the utilization of OprD protein, and the fact that it is not a substrate of the often upregulated MexAB/OprM efflux system of P. aeruginosa.

The biological chemistry, pharmacokinetics/pharmacodynamics, microbiologic spectrum, and clinical trials that led to the approval of ceftolozane is reviewed.

A discussion regarding its potential role in the treatment of complicated intra-abdominal infections and other infectious disease syndromes associated with drug-resistant pathogens follows.


September 18, 2015 at 3:34 pm

Descripción clínica y epidemiológica de un brote nosocomial por KPC en Buenos Aires, Argentina

Enf Inf & Microbiol Clínica 2012 V.30 N.7 P.376-79

Ezequiel Córdova a, María Inés Lespada a, Nora Gómez b, Fernando Pasterán c, Viviana Oviedo a y Claudia Rodríguez-Ismael a

a Grupo de Trabajo en Infectología, Hospital General de Agudos «Dr. Cosme Argerich», Buenos Aires, Argentina

b Laboratorio de Microbiología, Hospital General de Agudos «Dr. Cosme Argerich», Buenos Aires, Argentina c Servicio de Antimicrobianos, Departamento Bacteriología, Instituto Nacional de Enfermedades Infecciosas (INEI)-ANLIS «Dr. Carlos G. Malbrán», Buenos Aires, Argentina


Klebsiella pneumoniae (K. pneumoniae) productora de carbapenemasa tipo KPC (Kpn-KPC) representa un patógeno emergente, con elevada capacidad de diseminación nosocomial. El objetivo del presente estudio es describir las características clinico epidemiológicas de un brote nosocomial por KpnKPC en Buenos Aires, Argentina.


Estudio descriptivo y prospectivo. Se registraron los aspectos clinico epidemiológicos de pacientes con infección por Kpn-KPC (agosto de 2009 a julio de 2010). Se determinó la sensibilidad a los antimicrobianos mediante antibiograma por disco-difusión y por método automatizado (Vitek® 2 CbioMerieux). La búsqueda de carbapenemasa tipo KPC se realizó con la prueba de inhibición con 3-aminofenil-borónico (APB) y se confirmó su presencia por reacción en cadena de la polimerasa (PCR, por sus siglas en inglés). Se realizó tipificación molecular de las cepas aisladas por electroforesis en campo pulsado (PFGE, por sus siglas en inglés).


Se registraron 27 casos de infección por Kpn-KPC (sala de cirugía general: n = 8; clínica médica: n = 6; unidad de cuidados intensivos: n = 5; sala de emergencia: n = 4; otras: n = 4). Todos los aislamientos de Kpn-KPC pertenecieron a un mismo clon (ST258). Los sitios de infección fueron: tracto urinario (63%), tracto respiratorio (15%), abdomen (15%), sangre (7%) y hueso (4%). Todos los aislamientos de KPn-KPC fueron solamente sensibles a tigeciclina y colistina. Tratamiento empírico inadecuado: 63%. Tratamiento efectivo dirigido: colistina (74%), tigeciclina (4%), tigeciclina + colistina (22%). Mortalidad global: 59% (atribuible: 26%). Cultivos de vigilancia (hisopados) positivos: 7/70 (10%).


Se describe la emergencia de un brote nosocomial de Kpn-KPC en Buenos Aires, con alta capacidad de diseminación y elevada mortalidad. La implementación de medidas de control de infecciones es fundamental para reducir la transmisión nosocomial de Kpn-KPC



July 25, 2015 at 3:58 pm

Bacterial profile and patterns of antimicrobial drug resistance in intra-abdominal infections: current experience in a teaching hospital.

Indian J Pathol Microbiol. 2013 Oct-Dec;56(4):388-92.

Shree N, Arora BS1, Mohil RS, Kasana D, Biswal I.

1Department of Microbiology, Vardhman Mahavir Medical College & Safdarjang Hospital, New Delhi, India.



Bacterial isolates from intra-abdominal infections, in particular, peritonitis and their unpredictable antimicrobial resistance patterns, continue to be a matter of concern not only globally but regionally too.


An attempt in the present study was made to study the patterns of drug resistance in bacterial isolates, especially gram negative bacilli in intra-abdominal infections (IAI) in our hospital.


From 100 cases of peritonitis, identification of isolates was done as per recommended methods. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) testing were performed following the CLSI guidelines.


A total of 133 clinical isolates were obtained, of which 108 were aerobes and 22 anaerobes. Fungal isolates were recovered in only three cases. Escherichia coli (47/108) emerged as the most predominant pathogen followed by Klebsiella spp. (27/108), while Bacteroides fragilis emerged as the predominant anaerobe (12/22). Among coliforms, 61.7% E. coli and 74.1% Klebsiella spp. were ESBL positive. A high level of resistance was observed for beta lactams, ciprofloxacin, amikacin, and ertapenem. Ertapenem resistance (30-41%) seen in coliforms, appears as an important issue. Imipenem, tigecycline, and colistin were the most consistently active agents tested against ESBL producers.


Drug resistance continues to be a major concern in isolates from intra-abdominal infections. Treatment with appropriate antibiotics preceded by antimicrobial resistance testing aided by early diagnosis, adequate surgical management, and knowledge of antibiotic – resistant organisms appears effective in reducing morbidity and mortality in IAI cases.

FULL TEXT;year=2013;volume=56;issue=4;spage=388;epage=392;aulast=Shree

June 9, 2015 at 3:24 pm

Benefits of WSES guidelines application for the management of intra-abdominal infections

World J of Emerg Surg 2015

Belinda De Simone1*, Federico Coccolini2 , Fausto Catena1, Massimo Sartelli3, Salomone Di Saverio4,

Rodolfo Catena5, Antonio Tarasconi6 and Luca Ansaloni2

1 Department of Emergency and Trauma Surgery, University Hospital of Parma, Via Gramsci 11, 43100 Parma, Italy


May 24, 2015 at 5:34 pm

Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection

N Engl J Med 2015;372:1996-2005

R.G. Sawyer and Others


The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear.


We randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections.


Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, −0.5 percentage point; 95% confidence interval [CI], −7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, −4.0 days; 95% CI, −4.7 to −3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes.


In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT number, NCT00657566.)



N Engl J Med 2015;372:2062-2063


Antibiotics for Abdominal Sepsis

R.P. Wenzel and M.B. Edmond

From the Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond (R.P.W.); and the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (M.B.E.).

Major milestones in surgery have included safe sutures to promote tissue integrity, cautery to minimize bleeding, the use of anesthesia to avoid pain, and antisepsis to prevent operative contamination. In the antibiotic era, surgical procedures for source control in abdominal sepsis have been complemented with drugs targeting persistent organisms after luminal inflammation, obstruction, or perforation.

The appropriate duration of postsurgical antibiotic therapy has been unclear.1 However, if safe, shorter courses would be desirable to minimize drug-related adverse events, the selection of antibiotic resistance, and costs….



2015-05 EDIT Antibiotics for Abdominal Sepsis NEJM

May 22, 2015 at 8:55 am

Pelvic Inflammatory Disease

N Engl J Med 2015;372:2039-2048


R.C. Brunham, S.L. Gottlieb, and J. Paavonen

From the Department of Medicine, University of British Columbia, Vancouver, Canada (R.C.B.); the Department of Reproductive Health and Research, World Health Organization, Geneva (S.L.G.); and the Department of Obstetrics and Gynecology, University of Helsinki, Helsinki (J.P.).

Address reprint requests to Dr. Brunham at the Department of Medicine, University of British Columbia, 655 West 12th Ave., Vancouver, BC V5Z 4R4, Canada, or at

Pelvic inflammatory disease is an infection-induced inflammation of the female upper reproductive tract (the endometrium, fallopian tubes, ovaries, or pelvic peritoneum); it has a wide range of clinical manifestations.

Inflammation spreads from the vagina or cervix to the upper genital tract, with endometritis as an intermediate stage in the pathogenesis of disease.

The hallmark of the diagnosis is pelvic tenderness combined with inflammation of the lower genital tract; women with pelvic inflammatory disease often have very subtle symptoms and signs.

Many women have clinically silent spread of infection to the upper genital tract, which results in subclinical pelvic inflammatory disease….


May 20, 2015 at 9:07 pm

Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI)

Clin Infec Dis May 15, 2015 V.60 N.10 P.1462-1471

Joseph Solomkin, Ellie Hershberger, Benjamin Miller, Myra Popejoy, Ian Friedland, Judith Steenbergen, Minjung Yoon, Sylva Collins, Guojun Yuan, Philip S. Barie, and Christian Eckmann

1Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio

2Cubist Pharmaceuticals, Lexington, Massachusetts

3Departments of Surgery and Medicine, Weill Cornell Medical College, New York, New York

4Department of General, Visceral and Thoracic Surgery, Academic Hospital of Medical University Hannover, Peine, Germany

Correspondence: Joseph Solomkin, MD, Department of Surgery, University of Cincinnati College of Medicine, 6005 Given Rd, Cincinnati, Ohio 45243 (solomkjs{at} . 


Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae.


ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) every 8 hours or meropenem (1 g) every 8 hours intravenously for 4–14 days. The prospectively defined objectives were to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (24–32 days from start of therapy) in the microbiological intent-to-treat (primary) and microbiologically evaluable (secondary) populations using a noninferiority margin of 10%. Microbiological outcomes and safety were also evaluated.


Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in the primary (83.0% [323/389] vs 87.3% [364/417]; weighted difference, −4.2%; 95% confidence interval [CI], −8.91 to .54) and secondary (94.2% [259/275] vs 94.7% [304/321]; weighted difference, −1.0%; 95% CI, −4.52 to 2.59) endpoints, meeting the prespecified noninferiority margin. In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 95.8% (23/24) and 88.5% (23/26) in the ceftolozane/tazobactam plus metronidazole and meropenem groups, respectively, and 100% (13/13) and 72.7% (8/11) in patients with CTX-M-14/15 ESBLs. The frequency of adverse events (AEs) was similar in both treatment groups (44.0% vs 42.7%); the most common AEs in either group were nausea and diarrhea.


Treatment with ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in adult patients with cIAI, including infections caused by multidrug-resistant pathogens.

Clinical Trials Registration.NCT01445665 and NCT01445678.


April 30, 2015 at 2:16 pm

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