Posts filed under ‘Infecciones intraabdominales’
Ceftazidime/avibactam: a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections.
Drug Des Devel Ther. 2016 Jul 26;10:2379-86.
Hidalgo JA1, Vinluan CM2, Antony N3.
1UTEP/UT Austin Cooperative Pharmacy Program, College of Health Sciences, University of Texas at El Paso, El Paso; Department of Pharmacy, College of Pharmacy, The University of Texas at Austin, Austin.
2UTEP/UT Austin Cooperative Pharmacy Program, College of Health Sciences, University of Texas at El Paso, El Paso; Department of Pharmacy, College of Pharmacy, The University of Texas at Austin, Austin; Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
3Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P. aeruginosa and avibactam is a novel nonbeta-lactam beta-lactamase inhibitor. Avycaz(®), the trade name for this new combination antibiotic, restores the activity of ceftazidime against some of the previously resistant pathogens. Avycaz was approved in 2015 for the treatment of complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections with the addition of metronidazole in patients with little to no other treatment options. This review article assesses the clinical trials and data that led to the approval of this antibiotic, in addition to its spectrum of activity and limitations.
Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories
Clin. Microbiol. Rev. July 2013 26(3): 604-630
Carey-Ann D. Burnham and Karen C. Carroll
aDepartments of Pathology & Immunology and Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
bDepartments of Pathology and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Clostridium difficile is a formidable nosocomial and community-acquired pathogen, causing clinical presentations ranging from asymptomatic colonization to self-limiting diarrhea to toxic megacolon and fulminant colitis. Since the early 2000s, the incidence of C. difficile disease has increased dramatically, and this is thought to be due to the emergence of new strain types.
For many years, the mainstay of C. difficile disease diagnosis was enzyme immunoassays for detection of the C. difficile toxin(s), although it is now generally accepted that these assays lack sensitivity. A number of molecular assays are commercially available for the detection of C. difficile.
This review covers the history and biology of C. difficile and provides an in-depth discussion of the laboratory methods used for the diagnosis of C. difficile infection (CDI).
In addition, strain typing methods for C. difficile and the evolving epidemiology of colonization and infection with this organism are discussed.
Finally, considerations for diagnosing C. difficile disease in special patient populations, such as children, oncology patients, transplant patients, and patients with inflammatory bowel disease, are described.
As detection of C. difficile in clinical specimens does not always equate with disease, the diagnosis of C. difficile infection continues to be a challenge for both laboratories and clinicians.
Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).
World J Emerg Surg. 2016 Jul 15;11:33.
Sartelli M, Weber DG, Ruppé E, Bassetti M, Wright BJ, Ansaloni L, Catena F, Coccolini F, Abu-Zidan FM, Coimbra R, Moore EE, Moore FA, Maier RV, De Waele JJ, Kirkpatrick AW, Griffiths EA, Eckmann C, Brink AJ, Mazuski JE, May AK, Sawyer RG, Mertz D, Montravers P, Kumar A, Roberts JA, Vincent JL, Watkins RR, Lowman W, Spellberg B, Abbott IJ, Adesunkanmi AK, Al-Dahir S, Al-Hasan MN, Agresta F, Althani AA, Ansari S, Ansumana R, Augustin G, Bala M, Balogh ZJ, Baraket O, Bhangu A, Beltrán MA, Bernhard M, Biffl WL, Boermeester MA, Brecher SM, Cherry-Bukowiec JR, Buyne OR, Cainzos MA, Cairns KA, Camacho-Ortiz A, Chandy SJ, Che Jusoh A, Chichom-Mefire A, Colijn C, Corcione F, Cui Y, Curcio D, Delibegovic S, Demetrashvili Z, De Simone B, Dhingra S, Diaz JJ, Di Carlo I, Dillip A, Di Saverio S, Doyle MP, Dorj G, Dogjani A, Dupont H, Eachempati SR, Enani MA, Egiev VN, Elmangory MM, Ferrada P, Fitchett JR, Fraga GP, Guessennd N, Giamarellou H, Ghnnam W, Gkiokas G, Goldberg SR, Gomes CA, Gomi H, Guzmán-Blanco M, Haque M, Hansen S, Hecker A, Heizmann WR, Herzog T, Hodonou AM, Hong SK, Kafka-Ritsch R, Kaplan LJ, Kapoor G, Karamarkovic A, Kees MG, Kenig J, Kiguba R, Kim PK, Kluger Y, Khokha V, Koike K, Kok KY, Kong V, Knox MC, Inaba K, Isik A, Iskandar K, Ivatury RR, Labbate M, Labricciosa FM, Laterre PF, Latifi R, Lee JG, Lee YR, Leone M, Leppaniemi A, Li Y, Liang SY, Loho T, Maegele M, Malama S, Marei HE, Martin-Loeches I, Marwah S, Massele A, McFarlane M, Melo RB, Negoi I, Nicolau DP, Nord CE, Ofori-Asenso R, Omari AH, Ordonez CA, Ouadii M, Pereira Júnior GA, Piazza D, Pupelis G, Rawson TM, Rems M, Rizoli S, Rocha C, Sakakhushev B, Sanchez-Garcia M, Sato N, Segovia Lohse HA, Sganga G, Siribumrungwong B, Shelat VG, Soreide K, Soto R, Talving P, Tilsed JV, Timsit JF, Trueba G, Trung NT, Ulrych J, van Goor H, Vereczkei A, Vohra RS, Wani I, Uhl W, Xiao Y, Yuan KC, Zachariah SK, Zahar JR, Zakrison TL, Corcione A, Melotti RM, Viscoli C, Viale P.
Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy.
Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance.
The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally.
The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs.
The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections).
The authors hope that AGORA, involving many of the world’s leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.
Antimicrobial susceptibility of Gram-negative bacilli of community acquired intra-abdominal infections in a hospital at Buenos Aires, Argentina.
Rev Esp Quimioter. 2016 Jun 17.
Article in Spanish
Morganti L1, Córdova E, Cassini E, Gómez N, López Moral L, Badía M, Rodríguez C.
1Laura Morganti, Hospital General de Agudos Cosme Argerich. Pi y Margall 750, Ciudad Autónoma de Buenos Aires. Argentina. email@example.com.
Community acquired complicated intra-abdominal infections (cIAI) are a common condition. Few data are available about the level of antimicrobial resistance of Gram-negative bacteria isolated from community acquired cIAIs in Argentina.
Retrospective-prospective observational study (March 2010 to February 2012). Gram-negative bacteria antimicrobial susceptibility of isolates from community acquired cIAIs were evaluated.
During this period, a total of 85 patients were included and 138 pathogens were collected. Male sex: 58%. Median age: 33. Monomicrobial cultures were obtained in 49% of the cases. Ninety (65%) corresponded to Gram-negative organisms, and 48 (38%) to Gram-positive cocci. Gram-negative organisms most frequently observed were: Escherichia coli 76%, Klebsiella pneumoniae 8%, Pseudomonas aeruginosa 7% and Enterobacter spp. 6%. E. coli and K. pneumoniae showed a high percentage of strains resistance to ciprofloxacin of 37% and 29%, respectively. Similarly, resistance to ampicillin/sulbactam was observed in a 16% of the E. coli isolates. The prevalence of multiresistant Gram-negative organisms was 38%.
A high level of resistance to antimicrobials was observed in community acquired cIAIs, mainly to ciprofloxacin and ampicillin/sulbactam two of the most used antimicrobial for empirically treatment of cIAIs in our country. In addition a significant proportion of multiresistant Gram-negative organisms were identified.
Review of the guidelines for complicated skin and soft tissue infections and intra-abdominal infections–are they applicable today?
Clin Microbiol Infect. 2008 Dec;14 Suppl 6:9-18.
1Hospital Clínico Universitario, Medical School, Santiago de Compostela, Spain. firstname.lastname@example.org
Difficult-to-treat infections in surgical patients, such as serious skin and soft tissue infections (SSTIs) and complicated intra-abdominal infections (cIAIs), are the cause of significant morbidity and mortality, and carry an economic burden. These surgical site infections are typically polymicrobial infections caused by a plethora of pathogens, which include difficult-to-treat organisms and multiresistant Gram-positive and Gram-negative strains. Optimal management of SSTIs and cIAIs must take into account the presence of resistant pathogens, and depends on the administration of appropriate antimicrobial therapy (i.e. the correct spectrum, route and dose in a timely fashion for a sufficient duration as well as the timely implementation of source control measures). Treatment recommendations from the Infectious Diseases Society of America and the Surgical Infection Society are available for guidance in the management of both of these infections, yet the increased global prevalence of multidrug-resistant pathogens has complicated the antibiotic selection process. Several pathogens of concern include methicillin-resistant Staphylococcus aureus, responsible for problematic postoperative infections, especially in patients with SSTIs, extended-spectrum beta-lactamase-producing Gram-negative bacteria, including CTX-M-type-producing Escherichia coli strains, and multidrug-resistant strains of Bacteroides fragilis. New empirical regimens, taking advantage of potent broad-spectrum antibiotic options, may be needed for the treatment of certain high-risk patients with surgical site infections.
Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program.
Clin Infect Dis. 2016 Jun 1;62(11):1380-9.
Mazuski JE1, Gasink LB2, Armstrong J3, Broadhurst H3, Stone GG4, Rank D5, Llorens L5, Newell P3, Pachl J6.
1Washington University School of Medicine, St Louis, Missouri.
2AstraZeneca, Wilmington, Delaware.
3AstraZeneca, Alderley Park, United Kingdom.
4AstraZeneca, Waltham, Massachusetts.
5Actavis, Oakland, California.
6The Charles University, Prague, Czech Republic.
When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239).
The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of -12.5%.
Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, -3.5%; 95% confidence interval -8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (-2.4%; -6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (-0.8%; -4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen’s own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups.
Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone.
CLINICAL TRIALS REGISTRATION: NCT01499290 and NCT01500239.
Rev Chilena Infectol. 2013 Aug;30(4):417-25.
[Article in Spanish]
Sedano R1, Fica A, Guiñez D, Braun S, Porte L, Dabanch J, Weitzel T, Soto A.
1Departamento de Medicina, Hospital Militar de Santiago, Santiago, Chile.
Listeria monocytogenes infections have been poorly characterized in Chile.
To evaluate clinical manifestations and risk factors associated to a fatal outcome in a series of patients.
retrospective analysis of cases from 1991 to 2012.
Twenty three cases were identified, including 2 diagnosed after prolonged hospitalization (8.7%) with an average age of 68.4 years (range 44-90). Known predisposing factors were age > 65 years (60.9%), diabetes mellitus (40.9%), and immunosuppression (27.3%). Most cases presented after 2003 (70%). No cases associated with neonates, pregnancy or HIV infections were recorded. Patients presented with central nervous system (CNS) infection (39%), including 8 cases of meningitis and one of rhomboencephalitis; bacteremia (43.5%), including one case with endocarditis; abscesses (8.7%); and other infections (spontaneous bacterial peritonitis and pneumonia; 8.7%). Risky food consumption was found in 80% of those asked about it. Predominant clinical manifestations were fever (90.9%), and confusion (63.6%). CNS infections were associated to headache (OR 21, p < 0.05), nausea and vomiting (OR 50, p < 0.01). Only 45.5% received initial appropriate empirical therapy and 36.4% a synergistic combination. Eight patients died (34.8%), this outcome was associated to bacteremia (OR 8.25; IC95 1.2-59 p < 0.05).
monocytogenes infections appear to be increasing in Chile, causing infections in different sites, attacking vulnerable patients, and have a high case-fatality ratio, especially among those with bacteremia.