Imipenem resistance of Pseudomonas in pneumonia: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Pneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by <it>Pseudomonas aeruginosa </it>(PA), ~20% of which in observational studies are resistant to imipenem. We sought to identify the burden of PA imipenem resistance in pneumonia.</p> <p>Methods</p> <p>We conducted a systematic literature review of randomized controlled trials (RCT) of imipenem treatment for pneumonia published in English between 1993 and 2008. We extracted study, population and treatment characteristics, and proportions caused by PA. Endpoints of interest were: PA resistance to initial antimicrobial treatment, clinical success, microbiologic eradication and on-treatment emergence of resistance of PA.</p> <p>Results</p> <p>Of the 46 studies identified, 20 (N = 4,310) included patients with pneumonia (imipenem 1,667, PA 251; comparator 1,661, PA 270). Seven were double blind, and 7 included US data. Comparator arms included a β-lactam (17, [penicillin 6, carbapenem 4, cephalosporin 7, monobactam 1]), aminoglycoside 2, vancomycin 1, and a fluoroquinolone 5; 5 employed double coverage. Thirteen focused exclusively on pneumonia and 7 included pneumonia and other diagnoses. Initial resistance was present in 14.6% (range 4.2-24.0%) of PA isolates in imipenem and 2.5% (range 0.0-7.4%) in comparator groups. Pooled clinical success rates for PA were 45.2% (range 0.0-72.0%) for imipenem and 74.9% (range 0.0-100.0%) for comparator regimens. Microbiologic eradication was achieved in 47.6% (range 0.0%-100.0%) of isolates in the imipenem and 52.8% (range 0.0%-100.0%) in the comparator groups. Resistance emerged in 38.7% (range 5.6-77.8%) PA isolates in imipenem and 21.9% (range 4.8-56.5%) in comparator groups.</p> <p>Conclusions</p> <p>In the 15 years of RCTs of imipenem for pneumonia, PA imipenem resistance rates are high, and PA clinical success and microbiologic eradication rates are directionally lower for imipenem than for comparators. Conversely, initial and treatment-emergent resistance is more likely with the imipenem than the comparator regimens.</p

Membrane-based therapeutic plasma exchange in dogs: Prescription, anticoagulation, and metabolic response.

BACKGROUND Therapeutic plasma exchange (TPE) is used increasingly in small animals to remove circulating large molecular products such as antibodies, pathogenic proteins, and protein-bound toxins. Specific, efficient, and safe protocols need to be developed. HYPOTHESIS/OBJECTIVES To describe the technique of membrane-based TPE, the resulting physiological and metabolic changes, and to define an adequate regional citrate anticoagulation protocol. ANIMALS Thirty-four dogs treated with TPE (2011-2017). METHODS Retrospective review of all TPE treatments performed at the Vetsuisse Faculty, University of Bern, identified through a search of the institutional database for extracorporeal treatments. RESULTS Sixty-four treatments were performed, resulting in 1.0 plasma volume exchange (range, 0.4-1.1). Replacement fluids included fresh frozen plasma (12%-100% volume), colloids (0%-52%), human albumin (0%-41%), and saline (0%-70%). Anticoagulation was performed with regional citrate (n = 24), systemic heparinization (n = 2), or combined (n = 38). Main relevant laboratory changes included a 24.7% decrease in total proteins (interquartile range, 16.7-31.4; P < .001), 53% in fibrinogen (-30 to 63; P = .009), 36% in bilirubin (13-43, P = .02), 9.0% in urea (0.7-15.7; P < .001), and 4.5% in creatinine (-6.6 to 10.6; P = .006). Citrate accumulation was evidenced in all dogs, more pronounced in those with renal but not with hepatic impairment. Maximal tolerable citrate rates were estimated as 5.5 and 9.0 μmol/kg/min for treatments in dogs with and without renal impairment, respectively. Complications were observed in 22 treatments (34%) and were fatal in 2 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE Therapeutic plasma exchange causes metabolic and biochemical alterations. Understanding these effects makes possible to anticipate most complications and to improve safety of the procedure

The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome Registry: the Swiss connection

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) was initially described as an uncommon and usually fatal disorder. With effective treatment it is more frequently diagnosed, the clinical presentations are more diverse, and long-term sequelae are becoming recognized. METHODS: Patient data are from The Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry, an inception cohort of 348 consecutive patients with their first episode of clinically diagnosed TTP or HUS, 1989-2006. The Registry enrolls all patients in a defined region who are diagnosed with TTP or HUS and for whom plasma exchange treatment is requested. ADAMTS13 activity has been analyzed on 235 (93%) of 254 patients since 1995 at the University of Berne, Switzerland. Patients are described by clinical categories, related to their associated conditions and clinically apparent etiologies, and by the presence of severe ADAMTS13 deficiency. RESULTS AND CONCLUSIONS: The clinical spectrum of syndromes described as TTP is variable with multiple etiologies. Advances in clinical and laboratory investigation have provided better understanding of the pathogenesis of these syndromes, their clinical evaluation and management, and their long-term outcomes. In addition to new information about TTP, these studies provide a model for translational research to define the complete community spectrum of uncommon disorders