Posts filed under ‘Infecciones sitio quirurgico’

Carbapenem-Resistant Enterobacteriaceae Infections: Results From a Retrospective Series and Implications for the Design of Prospective Clinical Trials

Open Forum Infectious Diseases April 2017 V.4 N.2

Elizabeth L. Alexander; Jeffery Loutit; Mario Tumbarello; Richard Wunderink; Tim Felton …


The increasing incidence of multidrug-resistant Gram negatives, such as carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a critical need for new antimicrobials. Most studies of new antimicrobials have been performed in patients with nondrug-resistant pathogens. We performed a retrospective analysis of patients with CRE infections to inform the design of phase 3 clinical trials.


This was a retrospective study at 22 centers in 4 countries. Baseline data, treatment, and outcomes were collected in patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and bacteremia due to CRE.


Two hundred fifty-six cases of CRE infection were identified: 75 cUTI/AP, 21 HABP, 20 VABP, and 140 bacteremia. The patient population had significant comorbidities: 32.8% had chronic renal insufficiency, and 26.2% were immunocompromised. Illness severity at presentation was high: 29.3% presented with septic shock. Treatment regimens varied widely; however, a majority of patients received combination therapy. Outcomes were universally poor (28-day mortality was 28.1%) across all sites of infection, particularly in dialysis patients and those with sepsis.


The CRE infections occured in patients with substantial comorbidities and were associated with high mortality and low rates of clinical cure with available antibiotics. Patients with these comorbidities are often excluded from enrollment in clinical trials for registration of new drugs. These results led to changes in the inclusion/exclusion criteria of a phase 3 trial to better represent the patient population with CRE infections and enable enrollment. Observational studies may become increasingly important to guide clinical trial design, inform on the existing standard of care, and provide an external control for subsequent trials.



September 3, 2017 at 6:51 pm

In vitro activity of tedizolid and linezolid against Staphylococcus epidermidis isolated from prosthetic joint infections

European Journal of Clinical Microbiology & Infectious Diseases September 2017 V.36 N.9 P. 1549–1552

Littorin, B. Hellmark, Å. Nilsdotter-Augustinsson & B. Söderquist

1.School of Medical Sciences, Faculty of Medicine and HealthÖrebro UniversityÖrebroSweden

2.Department of Laboratory Medicine, Clinical MicrobiologyÖrebro University HospitalÖrebroSweden

3.Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health SciencesLinköping UniversityLinköpingSweden

4.Department of Infectious DiseasesCounty Council of ÖstergötlandLinköpingSweden

5.Departments of Infectious Diseases and Laboratory Medicine, Clinical MicrobiologyÖrebro University HospitalÖrebroSweden

Prosthetic joint infections (PJIs) are rare but long-lasting and are serious complications without any spontaneous resolution, requiring additional surgery and long-term treatment with antibiotics.

Staphylococci are the most important aetiological agents of PJIs, and among the coagulase-negative staphylococci Staphylococcus epidermidis is the most common.

However, S. epidermidis often displays multidrug resistance (MDR), demanding additional treatment options.

The objective was to examine the effectiveness of tedizolid and linezolid against S. epidermidis isolated from PJIs. The standard antibiotic susceptibility pattern of S. epidermidis (n = 183) obtained from PJIs was determined by disc diffusion test, and MIC was determined by Etest for tedizolid, linezolid, and vancomycin.

Tedizolid displayed MIC values ranging from 0.094 to 0.5 mg/L (MIC50: 0.19 mg/L, MIC90: 0.38 mg/L), linezolid MIC values ranging from 0.25 to 2 mg/L (MIC50: 0.75 mg/L, MIC90: 1 mg/L), and vancomycin MIC values ranging from 0.5 to 3 mg/L (MIC50 and MIC90 both 2 mg/L).

According to the disc diffusion test, 153/183 (84%) isolates were resistant to ≥3 antibiotic groups, indicating MDR.

In conclusion, S. epidermidis isolates from PJIs were fully susceptible, and the MIC50 and MIC90 values for tedizolid were two- to four-fold dilution steps lower compared with linezolid.

Tedizolid is not approved, and there are no reports of long-term treatment, but it may display better tolerability and fewer adverse effects than linezolid; it thus could be a possible treatment option for PJIs, alone or in combination with rifampicin.



August 22, 2017 at 8:25 am

Finegoldia magna: a forgotten pathogen in prosthetic joint infection rediscovered by molecular biology.

Clin Infect Dis. 2009 Oct 15;49(8):1244-7.

Levy PY1, Fenollar F, Stein A, Borrione F, Raoult D.

Author information

1 Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes-Unité Mixte de Recherche, Centre National de la Recherche Scientifique 6236-Institut de Recherche et Developpement 198, Faculté de Médecine, Université de la Méditerranée, Marseille, France.


In this study, we describe 13 patients with prosthetic infections due to Finegoldia magna (2% of our tested series).

Patients presented with either polymicrobial infection after an open fracture or nosocomial infection after recent prosthesis implantation.

Molecular techniques are critical for diagnosis, and recommended antibiotic prophylaxis has poor activity against F. magna.


August 10, 2017 at 3:42 pm

Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study.

PLoS Med. 2017 Jul 10;14(7):e1002340.

Branch-Elliman W1,2,3, Ripollone JE4, O’Brien WJ3, Itani KMF2,5,6, Schweizer ML7,8, Perencevich E7,8, Strymish J1,2, Gupta K1,3,5.

Author information

1 Department of Medicine, VA Boston Healthcare System, West Roxbury, Massachusetts, United States of America.

2 Harvard Medical School, Boston, Massachusetts, United States of America.

3 VA Center for Healthcare Organization and Implementation Research, VA Boston Healthcare System, West Roxbury, Massachusetts, United States of America.

4 Boston University School of Public Health, Boston, Massachusetts, United States of America.

5 Boston University School of Medicine, Boston, Massachusetts, United States of America.

6 Department of Surgery, VA Boston Healthcare System, West Roxbury, Massachusetts, United States of America.

7 VA Comprehensive Access & Delivery Research & Evaluation, Iowa City VA Health Care System, Iowa City, Iowa, United States of America.

8 Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.



The optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs). Potential harms associated with combination regimens, including acute kidney injury (AKI) and Clostridium difficile infection (CDI), were also considered.


Using a multicenter, national Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam) versus either single agent alone (vancomycin or a beta-lactam) and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association between receipt of combination prophylaxis and SSI was found for the other types of surgeries evaluated, including orthopedic joint replacement procedures. In MRSA-colonized patients undergoing cardiac surgery, SSI occurred in 8/346 (2.3%) patients who received combination prophylaxis versus 4/100 (4.0%) patients who received vancomycin alone (crude RR 0.58, 95% CI 0.18, 1.88). Among MRSA-negative and -unknown cardiac surgery patients, SSIs occurred in 58/6,607 (0.9%) patients receiving combination prophylaxis versus 146/10,215 (1.4%) patients who received a beta-lactam alone (crude RR 0.61, 95% CI 0.45, 0.83). Based on these associations, the number needed to treat to prevent 1 SSI in MRSA-colonized patients is estimated to be 53, compared to 176 in non-MRSA patients. CDI incidence was similar in both exposure groups. Across all types of surgical procedures, risk of AKI was increased in the combination antimicrobial prophylaxis group (2,971/12,508 [23.8%] receiving combination versus 1,058/5,089 [20.8%] receiving vancomycin alone versus 7,314/52,504 [13.9%] receiving beta-lactam alone). We found a significant association between absolute risk of AKI and receipt of combination regimens across all types of procedures. If the observed association is causal, the number needed to harm for severe AKI following cardiac surgery would be 167. The major limitation of our investigation is that it is an observational study in a predominantly male population, which may limit generalizability and lead to unmeasured confounding.


There are benefits but also unintended consequences of antimicrobial and infection prevention strategies aimed at “getting to zero” healthcare-associated infections. In our study, combination prophylaxis was associated with both benefits (reduction in SSIs following cardiac surgical procedures) and harms (increase in postoperative AKI). In cardiac surgery patients, the difference in risk-benefit profile by MRSA status suggests that MRSA-screening-directed prophylaxis may optimize benefits while minimizing harms in this selected population. More information about long-term outcomes and patient and societal preferences regarding risk of SSI versus risk of AKI is needed to improve clinical decision-making.


August 10, 2017 at 8:40 am

Editorial – Vancomycin Prophylaxis for Total Joint Arthroplasty: Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than Cefazolin

Clinical Orthopaedics and Related Research July 2017 V.475 N.7 P.1762-1766


Daniel Wongworawat MD


July 30, 2017 at 3:00 pm

Efficacy of indefinite chronic oral antimicrobial suppression for prosthetic joint infection in the elderly: a comparative study

International Journal of Infectious Diseases July 2017 V.60 N.7 P.57-60


  1. Prendki, P. Sergent, A. Barrelet, E. Oziol, E. Beretti, M. Berlioz-Thibal, F. Bouchand, F.A. Dauchy, E. Forestier, G. Gavazzi, C. Ronde-Oustau, J. Stirnemann, A. Dinh


  • Antimicrobial suppression appears to be effective for prosthetic joint infection (PJI).
  • Antimicrobial suppression appears safe for PJI.
  • Antimicrobial suppression is an adequate option for elderly patients with PJI.


During prosthetic joint infection (PJI), surgical management is sometimes impossible and indefinite chronic oral antimicrobial suppression (ICOAS) may be the only option. The outcomes of elderly patients who benefited from ICOAS with strictly palliative intent were evaluated.


A national retrospective cohort study was performed in France, involving patients aged >75 years with a PJI who were managed with planned life-long ICOAS from 2009 to 2014. Patients who experienced an event were compared to those who did not. An event was defined as a composite outcome in patients undergoing ICOAS, including local or systemic progression of the infection, death, or discontinuation of antimicrobial therapy because of an adverse drug reaction.


Twenty-one patients were included, with a median age of 85 years (interquartile range 81–88 years). Eight of the 21 patients experienced an event: one had an adverse drug reaction, three had systemic progression of sepsis, and two had local progression. Two of the 21 patients died. No death was related to ICOAS or infection. There was no significant difference between the population with an event and the population free of an event with regard to demographic, clinical, and microbiological characteristics (p > 0.05).


ICOAS appeared to be an effective and safe option in this cohort.



July 30, 2017 at 12:54 pm

Is This the Carbapenemase Test We’ve Been Waiting for? A Multicenter Evaluation of the Modified Carbapenem Inactivation Method

Journal of Clinical Microbiology August 2017 V.55 N.8 P.2309-2312

Susan M. Butler-Wu and April N. Abbott

aDepartment of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

bDepartment of Pathology, Deaconess Health System, Evansville, Indiana, USA


A plethora of phenotypic methods exist for the detection of carbapenemases; however, clinical laboratories have struggled for years with accurate, objective phenotypic detection of carbapenemase activity in Enterobacteriaceae. In this issue of the Journal of Clinical Microbiology, V. M. Pierce et al. (J Clin Microbiol 55:2321–2333, 2017, report on a multicenter evaluation of the modified carbapenem inactivation method (mCIM). The high sensitivity, specificity, reproducibility, and ease of interpretation associated with the mCIM for Enterobacteriaceae will likely lead to its adoption by clinical laboratories.



Journal of Clinical Microbiology August 2017 V.55 N.8 P.2321-2333

Modified Carbapenem Inactivation Method for Phenotypic Detection of Carbapenemase Production among Enterobacteriaceae

Virginia M. Pierce, Patricia J. Simner, David R. Lonsway, Darcie E. Roe-Carpenter, J. Kristie Johnson, William B. Brasso, April M. Bobenchik, Zabrina C. Lockett, Angella Charnot-Katsikas, Mary Jane Ferraro, Richard B. Thomson Jr., Stephen G. Jenkins, Brandi M. Limbago, and Sanchita Das

aDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA

bDepartment of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

cDivision of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

dBeckman Coulter Diagnostics, Inc., West Sacramento, California, USA

eDepartment of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA

fBD Life Sciences–Diagnostic Systems, Sparks, Maryland, USA

gDepartment of Pathology and Laboratory Medicine, Lifespan Academic Medical Center, Providence, Rhode Island, USA

hDepartment of Pathology, University of Chicago Medical Center, Chicago, Illinois, USA

iDepartment of Pathology, NorthShore University HealthSystem, Evanston, Illinois, USA

jDepartment of Pathology and Laboratory Medicine, Weill-Cornell Medical College, New York, New York, USA

The ability of clinical microbiology laboratories to reliably detect carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) is an important element of the effort to prevent and contain the spread of these pathogens and an integral part of antimicrobial stewardship. All existing methods have limitations. A new, straightforward, inexpensive, and specific phenotypic method for the detection of carbapenemase production, the carbapenem inactivation method (CIM), was recently described. Here we describe a two-stage evaluation of a modified carbapenem inactivation method (mCIM), in which tryptic soy broth was substituted for water during the inactivation step and the length of this incubation was extended. A validation study was performed in a single clinical laboratory to determine the accuracy of the mCIM, followed by a nine-laboratory study to verify the reproducibility of these results and define the zone size cutoff that best discriminated between CP-CRE and members of the family Enterobacteriaceae that do not produce carbapenemases. Bacterial isolates previously characterized through whole-genome sequencing or targeted PCR as to the presence or absence of carbapenemase genes were tested for carbapenemase production using the mCIM; isolates with Ambler class A, B, and D carbapenemases, non-CP-CRE isolates, and carbapenem-susceptible isolates were included. The sensitivity of the mCIM observed in the validation study was 99% (95% confidence interval [95% CI], 93% to 100%), and the specificity was 100% (95% CI, 82% to 100%). In the second stage of the study, the range of sensitivities observed across nine laboratories was 93% to 100%, with a mean of 97%; the range of specificities was 97% to 100%, with a mean of 99%. The mCIM was easy to perform and interpret for Enterobacteriaceae, with results in less than 24 h and excellent reproducibility across laboratories.



July 26, 2017 at 9:25 am

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