Archive for April, 2015

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 Infec Dis May 15, 2015 V.60 N.10 P.1462-1471

Joseph Solomkin, Ellie Hershberger, Benjamin Miller, Myra Popejoy, Ian Friedland, Judith Steenbergen, Minjung Yoon, Sylva Collins, Guojun Yuan, Philip S. Barie, and Christian Eckmann

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

Correspondence: Joseph Solomkin, MD, Department of Surgery, University of Cincinnati College of Medicine, 6005 Given Rd, Cincinnati, Ohio 45243 (solomkjs{at} . 


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.


April 30, 2015 at 2:16 pm

Factors associated with treatment failure in vertebral osteomyelitis requiring spinal instrumentation.

Antimicrob Agents Chemother. 2014;58(2):880-4.

Arnold R1, Rock C, Croft L, Gilliam BL, Morgan DJ.

1Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.


Patients with vertebral osteomyelitis may require instrumentation for spinal stabilization. Determining the optimal duration and type of antimicrobial therapy for these patients is challenging.

The aim of this study was to examine risk factors for treatment failure, in particular antimicrobial duration, in a cohort of patients requiring spinal instrumentation for vertebral osteomyelitis.

We conducted a retrospective cohort study of all patients with vertebral osteomyelitis who had spinal instrumentation between January 2002 and January 2012 at the University of Maryland Medical Center.

The primary outcome measure was treatment failure >4 weeks postoperatively.

We identified 131 patients with vertebral osteomyelitis requiring spinal instrumentation, 94 of whom had >4 weeks of follow-up and were included in the primary analysis. Treatment failure occurred in 22 of the 94 patients (23%) at a median of 4 months after surgery.

Among patients who failed therapy, 20 of 22 failed within 1 year of surgery. Cervical and thoracic infection sites and the presence of negative cultures were associated with fewer treatment failures.

Addition of rifampin and the use of chronic suppressive antimicrobials did not affect treatment failure rate.

Twenty-three percent of patients with spinal instrumentation for vertebral osteomyelitis experienced treatment failure.

Treatment failure almost always occurred within the first year of spinal instrumentation


April 30, 2015 at 2:11 pm

Asymptomatic bacteriuria in adults.

Am Fam Physician. 2006 Sep 15;74(6):985-90.

Colgan R1, Nicolle LE, McGlone A, Hooton TM.

1Dept of Family Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.


A common dilemma in clinical medicine is whether to treat asymptomatic patients who present with bacteria in their urine.

There are few scenarios in which antibiotic treatment of asymptomatic bacteruria has been shown to improve patient outcomes. Because of increasing antimicrobial resistance, it is important not to treat patients with asymptomatic bacteriuria unless there is evidence of potential benefit.

Women who are pregnant should be screened for asymptomatic bacteriuria in the first trimester and treated, if positive. Treating asymptomatic bacteriuria in patients with diabetes, older persons, patients with or without indwelling catheters, or patients with spinal cord injuries has not been found to improve outcomes.


April 26, 2015 at 7:41 pm

Osteomyelitis: a descriptive study.

Clin Orthop Surg. 2014 Mar;6(1):20-5.

Prieto-Pérez L1, Pérez-Tanoira R2, Petkova-Saiz E1, Pérez-Jorge C2, Lopez-Rodriguez C1, Alvarez-Alvarez B1, Polo-Sabau J1, Esteban J2.

1Department of Internal Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain.

2Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, Madrid, Spain.



To analyze the incidence and clinical-microbiological characteristics of osteomyelitis (OM) in a tertiary Spanish hospital.


All cases diagnosed with OM between January 2007 and December 2010 were retrospectively reviewed. The variables examined include epidemiological characteristics, risk factors, affected bone, radiographic changes, histology, microbiological culture results, antibiotic treatment, and the need for surgery.


Sixty-three cases of OM were diagnosed. Twenty-six patients (41.3%) had acute OM whereas 37 patients (58.7%) were classified as chronic OM. OM may result from haematogenous or contiguous microbial seeding. In this group, 49 patients (77.8%) presented with OM secondary to a contiguous source of infection and 14 patients had hematogenous OM (22.2%). Staphylococcus aureus was the most commonly found microorganism.


OM mainly affected patients with risk factors related to the presence of vascular diseases. Antibiotic treatment must be guided by susceptibility patterns of individual microorganisms, although it must be performed together with surgery in most of the cases.


April 26, 2015 at 7:39 pm

Systemic antibiotic therapy for chronic osteomyelitis in adults.

Clin Infect Dis. 2012 Feb 1;54(3):393-407.

Spellberg B1, Lipsky BA.

1Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA 90502, USA.


The standard recommendation for treating chronic osteomyelitis is 6 weeks of parenteral antibiotic therapy.

However, oral antibiotics are available that achieve adequate levels in bone, and there are now more published studies of oral than parenteral antibiotic therapy for patients with chronic osteomyelitis.

Oral and parenteral therapies achieve similar cure rates; however, oral therapy avoids risks associated with intravenous catheters and is generally less expensive, making it a reasonable choice for osteomyelitis caused by susceptible organisms.

Addition of adjunctive rifampin to other antibiotics may improve cure rates.

The optimal duration of therapy for chronic osteomyelitis remains uncertain. There is no evidence that antibiotic therapy for >4-6 weeks improves outcomes compared with shorter regimens.

In view of concerns about encouraging antibiotic resistance to unnecessarily prolonged treatment, defining the optimal route and duration of antibiotic therapy and the role of surgical debridement in treating chronic osteomyelitis are important, unmet needs.


April 26, 2015 at 7:37 pm

The diagnosis of urinary tract infection: a systematic review.

Dtsch Arztebl Int. 2010 May;107(21):361-7.

Schmiemann G1, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-Pradier E.

1Institut für Allgemeinmedizin, Medizinische Hochschule Hannover, Hannover, Germany.



Urinary tract infections (UTI) are among the leading reasons for treatment in adult primary care medicine, accounting for a considerable percentage of antibiotic prescriptions. Because this problem is so common and so significant in routine clinical practice, a high level of diagnostic accuracy is essential. Antibiotics should not be prescribed excessively, particularly in view of the increasing prevalence of antibiotic resistance.


Systematic review of relevant articles that were retrieved by a search of the Medline, Embase, and Cochrane Library databases. The recommendations of selected international guidelines were also taken into account, as were the German national quality standards for microbiological diagnosis.


The diagnosis of UTI by clinical criteria alone has an error rate of approximately 33%. The use of refined diagnostic algorithms does not completely eliminate uncertainty.


With the aid of a small number of additional diagnostic criteria, antibiotic treatment for UTI can be provided more specifically and thus more effectively. Differentiating UTI from asymptomatic bacteriuria, which usually requires no treatment, can lower the frequency of unnecessary antibiotic prescriptions.


April 25, 2015 at 9:31 pm

Salmonella enteritidis bacteraemia as clinical onset of acquired immune deficiency syndrome.

Rev Esp Anestesiol Reanim. 2013 Feb;60(2):103-5.

Article in Spanish

Ayelo Navarro A1, Gerónimo Pardo M, Torres Lamberti V, Mateo Cerdán CM, Jiménez Vizuete JM, Peyro García R.

Author information

1Sección de Anestesia y Reanimación, Hospital General de Almansa, Almansa, Albacete, España.


The case is presented of a 38 year-old patient who was admitted in the Emergency Department due to a severe acute respiratory failure and who was transferred to the Critical Care Unit with a suspected initial diagnosis of community acquired pneumonia caused by an atypical microorganism, which was complicated with an acute respiratory distress syndrome.

This was able to be treated with non-invasive mechanical ventilation. At 48 hours after admission, the growth of Gram negative bacilli in the blood culture was reported, which was subsequently identified as Salmonella enteritidis.

This information, along with the lymphopenia suffered by the patient, suggested an immunodepressed state, thus serological tests were performed which showed positive for HIV.

Antibiotic treatment was started based on the microbiological findings, with a favourable clinical outcome for the patient.


April 25, 2015 at 9:26 pm

Periprosthetic joint infections: a clinical practice algorithm.

Joints. 2015 Feb 13;2(4):169-74.

Volpe L1, Indelli PF2, Latella L3, Poli P1, Yakupoglu J4, Marcucci M3.

1Articular Replacements Excellence Center (CESAT) – Fondazione Onlus “…In Cammino…”, Fucecchio, Italy.

2New Mexico Veterans Affairs Health Care System (NMVAHCS) and Adult Reconstruction University of New Mexico, Department of Orthopaedics and Rehabilitation, Albuquerque, New Mexico, USA.

3Articular Replacements Excellence Center (CESAT) – Fondazione Onlus “…In Cammino…”, Fucecchio, Italy ; Orthopedic Clinic, University of Florence School of Medicine, Italy.

4The Breyer Center for Overseas Studies, Stanford University in Florence, Italy.



periprosthetic joint infection (PJI) accounts for 25% of failed total knee arthroplasties (TKAs) and 15% of failed total hip arthroplasties (THAs).

The purpose of the present study was to design a multidisciplinary diagnostic algorithm to detect a PJI as cause of a painful TKA or THA.


from April 2010 to October 2012, 111 patients with suspected PJI were evaluated. The study group comprised 75 females and 36 males with an average age of 71 years (range, 48 to 94 years). Eighty-four patients had a painful THA, while 27 reported a painful TKA. The stepwise diagnostic algorithm, applied in all the patients, included: measurement of serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels; imaging studies, including standard radiological examination, standard technetium-99m-methylene diphosphonate (MDP) bone scan (if positive, confirmation by LeukoScan was obtained); and joint aspiration with analysis of synovial fluid.


following application of the stepwise diagnostic algorithm, 24 out of our 111 screened patients were classified as having a suspected PJI (21.7%). CRP and ESR levels were negative in 84 and positive in 17 cases; 93.7% of the patients had a positive technetium-labeled bone scan, and 23% a positive LeukoScan. Preoperative synovial fluid analysis was positive in 13.5%; analysis of synovial fluid obtained by preoperative aspiration showed a leucocyte count of > 3000 cells μ/l in 52% of the patients.


the present study showed that the diagnosis of PJI requires the application of a multimodal diagnostic protocol in order to avoid complications related to surgical revision of a misdiagnosed “silent” PJI.


Level IV, therapeutic case series.


April 23, 2015 at 3:26 pm

Zika virus infection, Philippines, 2012.

Emerg Infect Dis. 2015 Apr;21(4):722-4.


Alera MT, Hermann L, Tac-An IA, Klungthong C, Rutvisuttinunt W, Manasatienkij W, Villa D, Thaisomboonsuk B, Velasco JM, Chinnawirotpisan P, Lago CB, Roque VG Jr, Macareo LR, Srikiatkhachorn A, Fernandez S, Yoon IK.

Philippines-AFRIMS (Armed Forces Research Institute of Medical Sciences), Cebu City, Philippines (M.T. Alera, J.M. Velasco, C.B. Lago); University of Toronto, Toronto, Ontario, Canada (L. Hermann); AFRIMS, Bangkok, Thailand (L. Hermann, C. Klungthong, W. Rutvisuttinunt, W. Manasatienkij, B. Thaisomboonsuk, P. Chinnawirotpisan, L.R. Macareo, S. Fernandez, I.-K. Yoon); Cebu City Health Department, Cebu City (I.A. Tac-An, D. Villa); Department of Health, Manila, Philippines (V.G. Roque, Jr.); University of Massachusetts Medical School, Worcester, Massachusetts, USA (A. Srikiatkhachorn)

To the Editor: Zika virus (ZIKV), a mosquitoborne flavivirus, was first isolated from a rhesus monkey in Uganda in 1947. This positive-sense, single-stranded RNA virus (family Flaviviridae, genus Flavivirus) has a 10,794-nt genome and is most closely related to Spondweni virus. Phylogenetic analyses have revealed 2 major lineages: Asian and African ….


April 23, 2015 at 3:22 pm

Zika virus outside Africa.

Emerg Infect Dis. 2009 Sep;15(9):1347-50.

Hayes EB1.

1Barcelona Centre for International Health Research, Barcelona, Spain.


Zika virus (ZIKV) is a flavivirus related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses.

In 2007 ZIKV caused an outbreak of relatively mild disease characterized by rash, arthralgia, and conjunctivitis on Yap Island in the southwestern Pacific Ocean.

This was the first time that ZIKV was detected outside of Africa and Asia. The history, transmission dynamics, virology, and clinical manifestations of ZIKV disease are discussed, along with the possibility for diagnostic confusion between ZIKV illness and dengue.

The emergence of ZIKV outside of its previously known geographic range should prompt awareness of the potential for ZIKV to spread to other Pacific islands and the Americas.


April 23, 2015 at 3:20 pm

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