BackgroundMultidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections.MethodsData were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes.ResultsTwo-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11–24) and median Charlson Comorbidity Indexes of 4 (IQR, 3–6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR], 5.55; 95% confidence interval [CI], 2.14–14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40–6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24–5.38).ConclusionsCeftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.

Tendon injury is thought to involve both damage accumulation within the matrix and an accompanying cell response. While several studies have characterized cell and matrix response in chronically injured tendons, few have assessed the initial response of tendon to overloadinduced damage. In this study, we assessed cell response to cyclic loading. Fascicle bundles from the equine superficial digital flexor tendon were exposed to cyclic loading in vitro, designed to mimic a bout of high-intensity exercise. Changes in cell morphology and protein-level alterations in markers of matrix inflammation and degradation were investigated. Loading resulted in matrix damage, which was accompanied by cells becoming rounder.The inflammatory markers cyclooxygenase-2 and interleukin-6 were increased in loaded samples, as were matrix metalloproteinase-13 and the collagen degradation marker C1,2C. These results indicate upregulation of inflammatory and degradative pathways in response to overload-induced in vitro, which may be initiated by alterations in cell strain environment because of localized matrix damage. This provides important information regarding the initiation of tendinopathy, suggesting that inflammation may play an important role in the initial cell response to tendon damage. Full understanding of the early tenocyte response to matrix damage is critical in order to develop effective treatments for tendinopathy.

The role of inflammation in tendon injury is uncertain and a topic of current interest. In vitro studies of tendon accelerated overload damage can serve as a valuable source of information on the early stages of tendinopathy. Viable fascicle bundles from bovine flexor tendons were subjected to cyclic uniaxial loading from 1–10% strain. Immuno‐staining for inflammatory markers and matrix degradation markers was performed on the samples after mechanical testing. Loaded samples exhibited visible extracellular matrix damage, with disrupted collagen fibers and fiber kinks, and notable damage to the interfascicular matrix. Inflammatory markers COX‐2 and IL‐6 were only expressed in the cyclically loaded samples. Collagen degradation markers MMP‐1 and C1,2C were colocalized in many areas, with staining occurring in the interfascicular matrix or the fascicular tenocytes. These markers were present in control samples, but staining became increasingly intense with loading. Little MMP‐3 or MMP‐13 was evident in control sections. In loaded samples, some sections showed intense staining of these markers, again localized to interfascicular regions. This study suggests that inflammatory markers may be expressed rapidly after tendon overload exercise. Interestingly, both inflammation and damage‐induced matrix remodeling seem to be concentrated in, or in the vicinity of, the highly cellular interfascicular matrix. © 2015 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 33:889–897, 2015.

Cephalosporins are among the most commonly prescribed antibiotic classes due to their wide clinical utility and general tolerability, with approximately 1–3% of the population reporting a cephalosporin allergy. However, clinicians may avoid the use of cephalosporins in patients with reported penicillin allergies despite the low potential for cross-reactivity. The misdiagnosis of β-lactam allergies and misunderstanding of cross-reactivity among β-lactams, including within the cephalosporin class, often leads to use of broader spectrum antibiotics with poor safety and efficacy profiles and represents a serious obstacle for antimicrobial stewardship. Risk factors for cephalosporin allergies are broad and include female sex, advanced age, and a history of another antibiotic or penicillin allergy; however, cephalosporins are readily tolerated even among individuals with true immediate-type allergies to penicillins. Cephalosporin cross-reactivity potential is related to the structural R1 side chain, and clinicians should be cognizant of R1 side chain similarities when prescribing alternate β-lactams in allergic individuals or when new cephalosporins are brought to market. Clinicians should consider the low likelihood of true cephalosporin allergy when clinically indicated. The purpose of this review is to provide an overview of the role of cephalosporins in clinical practice, and to highlight the incidence of, risk factors for, and cross-reactivity of cephalosporins with other antibiotics.