Archive for August, 2016

Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee.

J Orthop Res. 2016 Feb;34(2):177-86.

Getzlaf MA1, Lewallen EA1, Kremers HM2, Jones DL1,3, Bonin CA1, Dudakovic A1, Thaler R1, Cohen RC4, Lewallen DG1, van Wijnen AJ1.

Author information

1Department of Orthopedic Surgery, Mayo Clinic, 200 1st St SW, Rochester, Minnesota 55905.

2Department of Health Sciences Research, College of Medicine, Mayo Clinic, 200 1st St SW, Rochester, Minnesota 55905.

3Department of Biomedical Engineering and Physiology, Mayo Clinic, 200 1st St SW, Rochester, Minnesota 55905.

4Reconstructive Research and Development, Stryker Orthopedics, 325 Corporate Drive, Mahwah, New Jersey 07430.


Like any foreign object, orthopaedic implants are susceptible to infection when introduced into the human body. Without additional preventative measures, the absolute number of annual prosthetic joint infections will continue to rise, and may exceed the capacity of health care systems in the near future. Bacteria are difficult to eradicate from synovial joints due to their exceptionally diverse taxonomy, complex mechanistic attachment capabilities, and tendency to evolve antibiotic resistance. When a primary orthopaedic implant fails from prosthetic joint infection, surgeons are generally challenged by limited options for intervention. In this review, we highlight the etiology and taxonomic groupings of bacteria known to cause prosthetic joint infections, and examine their key mechanisms of attachment. We propose that antimicrobial strategies should focus on the most harmful bacteria taxa within the context of occurrence, taxonomic diversity, adhesion mechanisms, and implant design. Patient-specific identification of organisms that cause prosthetic joint infections will permit assessment of their biological vulnerabilities. The latter can be targeted using a range of antimicrobial techniques that exploit different colonization mechanisms including implant surface attachment, biofilm formation, and/or hematogenous recruitment. We anticipate that customized strategies for each patient, joint, and prosthetic component will be most effective at reducing prosthetic joint infections, including those caused by antibiotic-resistant and polymicrobial bacteria


August 27, 2016 at 6:10 pm

Body mass and weight thresholds for increased prosthetic joint infection rates after primary total joint arthroplasty.

Acta Orthop. 2016;87(2):132-8.

Lübbeke A1, Zingg M1, Vu D2, Miozzari HH1, Christofilopoulos P1, Uçkay I1,2, Harbarth S3, Hoffmeyer P1.

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1a Division of Orthopedics and Trauma Surgery , Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland .

2b Division of Infectious Diseases , Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland .

3c Infection Control Program , Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland.



Obesity increases the risk of deep infection after total joint arthroplasty (TJA). Our objective was to determine whether there may be body mass index (BMI) and weight thresholds indicating a higher prosthetic joint infection rate.


We included all 9,061 primary hip and knee arthroplasties (mean age 70 years, 61% women) performed between March 1996 and December 2013 where the patient had received intravenous cefuroxime (1.5 g) perioperatively. The main exposures of interest were BMI (5 categories: < 24.9, 25-29.9, 30-34.9, 35-39.9, and ≥ 40) and weight (5 categories: < 60, 60-79, 80-99, 100-119, and ≥ 120 kg). Numbers of TJAs according to BMI categories (lowest to highest) were as follows: 2,956, 3,350, 1,908, 633, and 214, respectively. The main outcome was prosthetic joint infection. The mean follow-up time was 6.5 years (0.5-18 years).


111 prosthetic joint infections were observed: 68 postoperative, 16 hematogenous, and 27 of undetermined cause. Incidence rates were similar in the first 3 BMI categories (< 35), but they were twice as high with BMI 35-39.9 (adjusted HR = 2.1, 95% CI: 1.1-4.3) and 4 times higher with BMI ≥ 40 (adjusted HR = 4.2, 95% CI: 1.8-9.7). Weight ≥ 100 kg was identified as threshold for a significant increase in infection from the early postoperative period onward (adjusted HR = 2.1, 95% CI: 1.3-3.6).


BMI ≥ 35 or weight ≥ 100 kg may serve as a cutoff for higher perioperative dosage of antibiotics.


August 27, 2016 at 6:08 pm

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.

Author information

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.


August 27, 2016 at 12:27 pm

The Alpha-defensin Test for Periprosthetic Joint Infections Is Not Affected by Prior Antibiotic Administration.

Clin Orthop Relat Res. 2016 Jul;474(7):1610-5.

Shahi A1, Parvizi J1, Kazarian GS1, Higuera C2, Frangiamore S2, Bingham J3, Beauchamp C3, Valle CD4, Deirmengian C1,5.

Author information

1The Rothman Institute at Thomas Jefferson University Hospital, Philadelphia, PA, USA.

2Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH, USA.

3Department of Orthopaedic Surgery, Mayo Clinic Phoenix, Phoenix, AZ, USA.

4Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, USA.

5The Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA, 19096, USA.



Previous studies have demonstrated that the administration of antibiotics to patients before performing diagnostic testing for periprosthetic joint infection (PJI) can interfere with the accuracy of test results. Although a single-institution study has suggested that alpha-defensin maintains its concentration and sensitivity even after antibiotic treatment, this has not yet been demonstrated in a larger multiinstitutional study.


(1) For the evaluation of PJI, is prior antibiotic administration associated with decreased alpha-defensin levels? (2) When prior antibiotics are given, is alpha-defensin a better screening test for PJI than the traditional tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fluid white blood cells, fluid polymorphonuclear cells [PMNs], and fluid culture)?


This retrospective study included data from 106 hip and knee arthroplasties with Musculoskeletal Infection Society-defined PJI from four centers. Of the 106 patients in this study, 30 (28%) were treated with antibiotics for PJI before diagnostic workup (ABX group), and 76 (72%) were not treated before the diagnostic workup (NO-ABX group). There were no differences in age, sex, joint, culture-negative rate, or bacteriology between groups. The patients in the ABX group had antibiotics initiated by physicians who commenced care before assessment for PJI by the treating surgeon’s service. We compared the alpha-defensin levels and sensitivity between the ABX and NO-ABX groups. Additionally, the sensitivity of the alpha-defensin test was compared to that of traditional tests for PJI among patients on antibiotics.


The administration of antibiotics before performing the alpha-defensin test for PJI was not associated with a decreased median alpha-defensin level (ABX group, median 4.2 [range, 1.79-12.8 S/CO] versus NO-ABX, median 4.9 [range, 0.5-16.8 S/CO], difference of medians: 0.68 S/CO [95% confidence interval {CI}, -0.98 to 1.26], p = 0.451). Furthermore, the alpha-defensin test had a higher sensitivity (100%; 95% CI, 88.4%-100.0%) in diagnosing PJI among patients on antibiotics when compared with the ESR (69.0% [95% CI, 49.17%-84.72%], p = 0.001), the CRP (79.3% [95% CI, 60.3%-92.0%], p = 0.009), the fluid PMN% (79.3% [95% CI, 60.3%-92.0%), p = 0.009), and fluid culture (70.0% [95% CI, 50.6%-85.3%], p = 0.001).


The alpha-defensin test maintains its concentration and sensitivity for PJI even in the setting of antibiotic administration. Furthermore, among patients with PJI on antibiotics, the alpha-defensin tests demonstrated a higher sensitivity in detecting PJI when compared with the ESR, CRP, fluid PMN%, and fluid culture. The high sensitivity of the alpha-defensin test, even in the setting of prior antibiotic treatment, provides excellent utility as a screening test for PJI.


Level III, diagnostic study.


August 26, 2016 at 3:47 pm

Staphylococcus aureus small colony variants in prosthetic joint infection.

Clinical Infectious Diseases October 15, 2006 V.43 N.8 P.961-7.

Sendi P1, Rohrbach M, Graber P, Frei R, Ochsner PE, Zimmerli W.

Author information

1Unit of Infectious Diseases, Basel University Medical Clinic Liestal, Liestal, CH-4410, Switzerland.



Small colony variants of Staphylococcus aureus tend to persist despite antimicrobial therapy, especially when involved in implant-associated infections.


We analyzed 5 cases of hip prosthesis-associated infections due to small colony variants, including their course prior to identification of the pathogen. Biopsy investigations included microbiological examination and, in 1 case, transmission electron microscopy to detect intracellular bacteria in nonprofessional phagocytes. A treatment concept was elaborated on the basis of a published algorithm and patients were managed accordingly.


The patients’ mean age was 62.2 years. All patients experienced treatment failures prior to isolation of small colony variants, despite as many as 3 surgical revisions and up to 22 months of antibiotics. Transmission electron microscopy performed on biopsy specimens from periprosthetic tissue revealed intracellular cocci in fibroblasts. All prostheses were removed without implanting a spacer, and antimicrobial agents were administered for 5.5-7 weeks. Reimplantation of the prosthesis was performed for 4 patients. Follow-ups were uneventful in all 5 cases.


In the case of a poor response to adequate antimicrobial and surgical treatment in implant-associated staphylococcal infections, small colony variants should be considered and actively sought. In our case series, a 2-stage exchange without implantation of a spacer combined with antimicrobial therapy for an implant-free interval of 6-8 weeks was associated with successful outcome, with a mean follow-up of 24 months.


August 26, 2016 at 8:32 am

Extended-Infusion versus standard-infusion piperacillin-tazobactam for sepsis syndromes at a tertiary medical center.

Antimicrob Agents Chemother. 2014 Aug;58(8):4470-5.

Cutro SR1, Holzman R2, Dubrovskaya Y3, Chen XJ3, Ahuja T3, Scipione MR3, Chen D2, Papadopoulos J3, Phillips MS2, Mehta SA2.

Author information

1Division of Infectious Diseases, New York University School of Medicine, New York, New York, USA

2Division of Infectious Diseases, New York University School of Medicine, New York, New York, USA.

3Department of Pharmacy, New York University-Langone Medical Center, New York, New York, USA.


Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.


August 25, 2016 at 8:19 am

Effect of meropenem administration in extended infusion on the clinical outcome of febrile neutropenia: a retrospective observational study

J Antimicrob Chemother. 2014 Sep;69(9):2556-62.

Fehér C1, Rovira M2, Soriano A3, Esteve J2, Martínez JA4, Marco F5, Carreras E2, Martínez C2, Fernández-Avilés F2, Suárez-Lledó M2, Mensa J4.



Information on the efficacy of extended meropenem administration in neutropenic patients is scarce. Our objective was to determine whether the administration of meropenem in a 4 h extended infusion (EI) leads to a better clinical outcome in patients with febrile neutropenia than the conventional short infusion (SI).


This was a retrospective observational study. The subjects were neutropenic patients who presented with fever after receiving haematopoietic stem-cell transplantation or induction chemotherapy for acute myeloid leukaemia. The primary endpoint was the success of treatment after 5 days of meropenem therapy, defined as follows: the disappearance of fever leading to a maintained (≥ 24 h) feverless state; the resolution or improvement of the clinical signs and symptoms of infection; the absence of persistent or breakthrough bacteraemia; and no additional antibiotics prescribed because of an unsatisfactory clinical evolution.


Eighty-eight patients received meropenem (1 g/8 h) in SI and 76 received the same dose in EI. Treatment success on day 5 was superior in the EI group [52/76 (68.4%) versus 36/88 (40.9%); P<0.001]. Meropenem administered in EI was independently associated with success (OR 3.13, 95% CI 1.61-6.10). Fewer additional antibiotics were prescribed in the EI group during the first 5 days of treatment [20/76 (26.3%) versus 44/88 (50.0%); P=0.002]. Using Kaplan-Meier survival analysis a more prompt defervescence and a faster decrease in C-reactive protein concentration were observed in the EI group (P=0.021 and P=0.037, respectively). There were no significant differences in the length of hospital stay and in the mortality rate.


Meropenem administration in EI results in a better clinical outcome for febrile neutropenia episodes, with fewer additional antibiotics needed.


August 25, 2016 at 8:17 am

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