Posts filed under ‘Infecciones intraabdominales’
Ceftazidime/avibactam activity tested against Gram-negative bacteria isolated from bloodstream, pneumonia, intra-abdominal and urinary tract infections in US medical centres (2012).
J Antimicrob Chemother. 2014 Jun;69(6):1589-98.
Flamm RK1, Farrell DJ2, Sader HS2, Jones RN2.
1JMI Laboratories, North Liberty, IA, USA firstname.lastname@example.org
2JMI Laboratories, North Liberty, IA, USA.
The activity of ceftazidime/avibactam and comparator agents was monitored at 73 medical centres across all nine US census bureau regions during 2012.
Bacterial isolates were collected from patients hospitalized with pneumonia, urinary tract infections (UTI), intra-abdominal infections (IAI) and bloodstream infections (BSI). The study protocol predetermined the target numbers of strains for each of the requested bacterial species that sites were to collect. Isolates were determined to be clinically relevant at the medical centre and only one isolate per patient episode was collected.
There were 1466 Gram-negative isolates from BSI, 3245 from pneumonia patients, 501 from IAI and 2356 from UTI. Ceftazidime/avibactam was active against Enterobacteriaceae from each infection type. The MIC90 values for ceftazidime/avibactam against Enterobacteriaceae isolates from BSI, pneumonia patients, IAI or UTI were 0.25 mg/L. The extended-spectrum cephalosporin resistance rates for Escherichia coli were 8.5% (UTI), 10.4% (IAI), 12.7% (BSI) and 17.5% (pneumonia patients). The extended-spectrum cephalosporin resistance rates for Klebsiella spp. were 13.0% (UTI), 13.9% (BSI), 16.3% (IAI) and 19.3% (pneumonia patients). A total of 96.5% of the Pseudomonas aeruginosa isolates from BSI, 95.8% from pneumonia patients, 96.3% from IAI and 98.7% from UTI exhibited a ceftazidime/avibactam MIC of ≤8 mg/L (CLSI susceptible breakpoint for ceftazidime when tested alone against P. aeruginosa). Most tested agents showed limited activity against Acinetobacter baumannii, except for colistin. A total of 31.2% of A. baumannii displayed ceftazidime/avibactam MIC values of ≤8 mg/L.
Ceftazidime/avibactam demonstrated potent broad-spectrum activity against Gram-negative pathogens collected in the USA during 2012 from BSI, pneumonia patients, IAI and UTI.
Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial.
J Antimicrob Chemother. 2013 May;68(5):1183-92.
Lucasti C1, Popescu I, Ramesh MK, Lipka J, Sable C.
1South Jersey Infectious Diseases, Somers Point, NJ, USA. email@example.com
Avibactam, a novel non-β-lactam β-lactamase inhibitor, restores the in vitro activity of ceftazidime against class A, C and some class D β-lactamase-producing pathogens, including those commonly associated with complicated intra-abdominal infections (cIAIs). This randomized, active-controlled, double-blind, Phase II trial (NCT00752219) aimed to evaluate the safety and efficacy of ceftazidime/avibactam plus metronidazole compared with meropenem in hospitalized patients with cIAI.
Adults with confirmed cIAI requiring surgical intervention and antibiotics were randomized 1:1 to receive intravenously either (i) 2000 mg of ceftazidime plus 500 mg of avibactam plus a separate infusion of 500 mg of metronidazole or (ii) 1000 mg of meropenem plus placebo every 8 h for a minimum of 5 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 2 weeks after the last dose of study therapy.
Overall, 101 patients received ceftazidime/avibactam plus metronidazole; 102 received meropenem. The median duration of treatment was 6.0 and 6.5 days, respectively. Favourable clinical response at the TOC visit in the ME population was observed in 91.2% (62/68) and 93.4% (71/76) of patients in the ceftazidime/avibactam plus metronidazole and meropenem groups, respectively (observed difference: -2.2%; 95% CI: -20.4%, 12.2%). The incidence of treatment-emergent adverse events was similar for ceftazidime/avibactam plus metronidazole (64.4%) and meropenem (57.8%).
Ceftazidime/avibactam plus metronidazole was effective and generally well tolerated in patients with cIAI, with a favourable clinical response rate in the ME population of >90%, similar to that of meropenem.
Empiric therapy for hospital-acquired, Gram-negative complicated intra-abdominal infection and complicated urinary tract infections: a systematic literature review of current and emerging treatment options.
BMC Infect Dis. 2015 Aug 5;15:313.
1Tufts Medical Center, Department of Medicine, Division of Geographic Medicine and Infectious Disease, 800 Washington St, Boston, MA, 02446, USA. firstname.lastname@example.org
Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug-resistant organisms. Current treatment options for resistant Gram-negative infections include carbapenems, tigecycline, piperacillin-tazobactam, cefepime, ceftazidime, and two recently approved therapies, ceftolozane-tazobactam and ceftazidime-avibactam.
This systematic literature review surveys the published clinical trial evidence available since 2000 in support of both current and emerging treatment options in the settings of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI). When available, clinical cure rates for patients with infections from ESBL-producing strains are provided, as is information about efficacy against Pseudomonas aeruginosa.
Clinical trial evidence to guide selection of empiric antibiotic therapy in patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs is limited. Though most of the clinical trials explored in this overview enrolled patients with complicated infections, often patients with severe infections and multiple comorbidities were excluded.
Practitioners in the clinical setting who are treating patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs need to consider the possibility of polymicrobial infections, antibiotic-resistant organisms, and/or severely ill patients with multiple comorbidities. There is a severe shortage of evidence-based research to guide the selection of empiric antibiotic therapy for many patients in this setting. New therapies recently approved or in late-stage development promise to expand the number of options available for empiric therapy of these hospital-acquired, Gram-negative infections.
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.
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.
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
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.
MATERIALS AND METHODS:
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.
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