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.
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.
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 Infect Dis. 2015 May 15;60(10):1462-71.
Solomkin J1, Hershberger E2, Miller B2, Popejoy M2, Friedland I2, Steenbergen J2, Yoon M2, Collins S2, Yuan G2, Barie PS3, Eckmann C4.
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.
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.
Can J Infect Dis Med Microbiol. 2013 Summer;24(2):e45-6.
Bonenfant F1, Rousseau E1, Farand P1.
1Internal medicine division, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec.
Abstractin English, French
A previously healthy 58-year-old man presented with a septic thrombosis of the right hepatic vein and a pyogenic liver abscess (PLA) one week after undergoing a screening colonoscopy. Blood cultures and a radiological drainage specimen were both positive for Streptococcus anginosus. Evolution was favourable after six weeks of antibiotherapy. To the authors’ knowledge, the present report is the first to describe a PLA following a screening colonoscopy with no intervention. The authors hypothesize that silent microperforations during colonoscopy contributed to the infection. Although 20% to 40% of reported PLA cases are cryptogenic in the literature, it may be because of failure to recognize and report a precipitating factor such as colonoscopy. As more cases similar to the present case are reported, the number of cryptogenic cases may decrease.
Case Rep Infect Dis. 2014;2014:954046.
Livingston LV1, Perez-Colon E1.
1Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 17 Davis Boulevard, Suite 308, Tampa, FL 33606, USA.
Streptococcus intermedius is a member of the Streptococcus anginosus group of bacteria. This group is part of the normal flora of the oropharynx, genitourinary, and gastrointestinal tracts; however, they have been known to cause a variety of purulent infections including meningitis, endocarditis, and abscesses, even in immunocompetent hosts. In particular, S. intermedius has been associated with the development of liver and brain abscesses. There have been several case reports of S. intermedius liver abscesses with active periodontal infection. To our knowledge, however, there has not been a case following a routine dental procedure. In fact, the development of liver abscesses secondary to dental procedures is very rare in general, and there are only a few case reports in the literature describing this in relation to any pathogen. We present a rare case of S. intermedius bacteremia and liver abscess following a dental cleaning. This case serves to further emphasize that even routine dental procedures can place a patient at risk of the development of bacteremia and liver abscesses. For this reason, the clinician must be sure to perform a detailed history and careful examination. Timely diagnosis of pyogenic liver abscesses is vital, as they are typically fatal if left untreated.
JSLS. 2015 Jul-Sep;19(3). pii: e2015.00065.
Lachiewicz MP, Moulton LJ, Jaiyeoba O.
Surgical site infection (SSI) is a common complication of hysterectomy. Minimally invasive hysterectomy has lower infection rates than abdominal hysterectomy. The lower SSI rates reflect the role and benefit in infection control of having minimal incisions, rather than a large anterior abdominal wall incision. Despite the lower rates, SSI after laparoscopic hysterectomy is not uncommon.In this article, we review pre-, intra-, and postoperative risk factors for infection. Rates of postoperative fever after laparoscopic hysterectomy and when evaluation for infection is warranted in a febrile patient are also reviewed.
PubMed was searched for English-only articles using National Library of Medicine Medical Subject Headings(MESH) terms and keywords including but not limited to “postoperative,” “surgical site,” “infection,” “fever,” “laparoscopic,” “laparoscopy,” and “hysterectomy.”
Reducing hospital-acquired infections such as SSI is one of the more effective ways of improving patient safety. Knowledge and understanding of risk factors for infection following laparoscopic hysterectomy enable the gynecologic surgeon or hospital to implement targeted preventive measures.
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.