Modifiable Risk Factors for the Emergence of Ceftolozane-tazobactam Resistance.

BACKGROUND: Ceftolozane-tazobactam (TOL-TAZ) affords broad coverage against Pseudomonas aeruginosa. Regrettably, TOL-TAZ resistance has been reported. We sought to identify modifiable risk factors that may reduce the emergence of TOL-TAZ resistance. METHODS: Twenty-eight consecutive patients infected with carbapenem-resistant P. aeruginosa isolates susceptible to TOL-TAZ, treated with ≥72 hours of TOL-TAZ , and with P. aeruginosa isolates available both before and after TOL-TAZ exposure between January 2018 and December 2019 in Baltimore, Maryland, were included. Cases were defined as patients with at least a 4-fold increase in P. aeruginosa TOL-TAZ MICs after exposure to TOL-TAZ. Independent risk factors for the emergence of TOL-TAZ resistance comparing cases and controls were investigated using logistic regression. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance that emerged during TOL-TAZ therapy. RESULTS: Fourteen patients (50%) had P. aeruginosa isolates which developed at least a 4-fold increase in TOL-TAZ MICs(ie, cases). Cases were more likely to have inadequate source control (29% vs 0%, P = .04) and were less likely to receive TOL-TAZ as an extended 3-hour infusion (0% vs 29%; P = .04). Eighty-six percent of index isolates susceptible to ceftazidime-avibactam (CAZ-AVI) had subsequent P. aeruginosa isolates with high-level resistance to CAZ-AVI, after TOL-TAZ exposure and without any CAZ-AVI exposure. Common mutations identified in TOL-TAZ resistant isolates involved AmpC, a known binding site for both ceftolozane and ceftazidime, and DNA polymerase. CONCLUSIONS: Due to our small sample size, our results remain exploratory but forewarn of the potential emergence of TOL-TAZ resistance during therapy and suggest extending TOL-TAZ infusions may be protective. Larger studies are needed to investigate this association.

Endoscopic gastrointestinal anastomosis: a review of established techniques.

Technologic advancements in the field of therapeutic endoscopy have led to the development of minimally invasive techniques to create GI anastomosis without requiring surgery. Examples of the potential clinical applications include bypassing malignant and benign gastric outlet obstruction, providing access to the pancreatobiliary tree in those who have undergone Roux-en-Y gastric bypass, and relieving pancreatobiliary symptoms in afferent loop syndrome. Endoscopic GI anastomosis is less invasive and less expensive than surgical approaches, result in improved outcomes, and therefore are more appealing to patients and providers. The aim of this review is to present the evolution of luminal endoscopic gastroenteric and enteroenteric anastomosis dating back to the first compression devices and to describe the clinical techniques being used today, such as magnets, natural orifice transluminal endoscopic surgery, and EUS-guided techniques. Through continued innovation, endoscopic interventions will rise to the forefront of the therapeutic arsenal available for patients requiring GI anastomosis.

INSULIN AUTOIMMUNE SYNDROME IN A YOUNG CAUCASIAN WOMAN.

A young Caucasian woman presents several episodes of severe fasting hypoglycemia. Fasting lab tests revealed: glycemia 28 mg/dL, insulinemia 143.3 µU/mL, insulin antibodies above 100 U/mL, leading to the diagnosis of insulin autoimmune syndrome. Due to lack of clinical improvement after 2 months, prednisone was started at 0.5 mg/kg/day, and then tapered by 5 mg every 5 days. Three weeks after discontinuing corticotherapy, the patient had no more severe fasting hypoglycemia, but occasionally postprandial mild hypoglycemia. Fasting lab tests showed: glycemia 83 mg/dL, insulinemia 58.6 µU/mL. At 5 hours during oral glucose tolerance test glycemia was 33 mg/dL, insulinemia 152.9 µU/mL.

Does This Patient Need Blood Cultures? A Scoping Review of Indications for Blood Cultures in Adult Nonneutropenic Inpatients.

Guidance regarding indications for initial or follow-up blood cultures is limited. We conducted a scoping review of articles published between January 2004 and June 2019 that reported the yield of blood cultures and/or their impact in the clinical management of fever and common infectious syndromes in nonneutropenic adult inpatients. A total of 2893 articles were screened; 50 were included. Based on the reported incidence of bacteremia, syndromes were categorized into low, moderate, and high pretest probability of bacteremia. Routine blood cultures are recommended in syndromes with a high likelihood of bacteremia (eg, endovascular infections) and those with moderate likelihood when cultures from the primary source of infection are unavailable or when prompt initiation of antibiotics is needed prior to obtaining primary source cultures. In syndromes where blood cultures are low-yield, blood cultures can be considered for patients at risk of adverse events if a bacteremia is missed (eg, patient with pacemaker and severe purulent cellulitis). If a patient has adequate source control and risk factors or concern for endovascular infection are not present, most streptococci or Enterobacterales bacteremias do not require routine follow-up blood cultures.

Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum ß-Lactamase-Producing Organisms?

BACKGROUND: Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum ß-lactamase (ESBL)-producing organisms. METHODS: We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain. RESULTS: There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09). CONCLUSIONS: TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Treatment of multidrug-resistant Gram-negative skin and soft tissue infections.

PURPOSE OF REVIEW: The increase in skin and soft tissue infections (SSTI) because of multidrug-resistant (MDR) pathogens is a global concern. Although MDR Gram-negative bacteria (GNB) are often overlooked as a cause of SSTIs, their burden on the morbidity of many subgroups of patients is high. There is a paucity in the available treatment options and guidelines on how to treat these pathogens. This manuscript reviews the management of SSTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa (CRPA), Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. We also highlight a few novel antibiotics that show promise in the future management of MDR-GNB SSTIs. RECENT FINDINGS: Studies on treatment options of MDR-GNB SSTIs are scarce. Most clinical trials investigating new antibiotics have addressed conditions such as complicated intraabdominal infections, complicated urinary infections, and respiratory infections. CREs are a heterogenous group of pathogens with various mechanisms of resistance dictating susceptibility to different antimicrobial agents. Ceftazidime--avibactam, and meropenem--vaborbactam have potent activity against some of the CREs, especially Klebsiella pneumoniae carbapenemase (KPC) producers. Several novel antibiotics have potent activity against CRPA SSTIs, such as ceftazidime--avibactam, ceftolozane--tazobactam, cefiderocol, delafloxacin, finafloxacin, and murepavadin. Cefiderocol may also play an important role in the management of CRAB SSTIs, along with plazomicin and eravacycline. SUMMARY: MDR-GNB play a major role in SSTIs in patients with underlying immunodeficiency, as well as burn or trauma-related injuries. With the alarming global rise in MDR-GNB resistance, antibiotic therapy for SSTIs is challenging and must be guided by in-vitro susceptibility results. Currently, data extrapolated from other indications and combination therapy can be used empirically pending microbiological data and susceptibilities. Novel antibiotics are currently under development. It is hoped that future clinical trials will be designed to address MDR-GNB SSTIs.

The burden of laboratory-confirmed influenza infection in Lebanon between 2008 and 2016: a single tertiary care center experience.

BACKGROUND: Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon. METHODS: A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis. RESULTS: A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19-50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5-19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age (< 2 years and ≥ 65 years) were associated with a more severe course of disease, hospitalization, intensive care unit (ICU) admission, complications, and mortality rate. Of all the identified cases, 26% were hospitalized. Moderate-to-severe disease was more likely in influenza B cases but no difference in mortality was reported between the two types. Antivirals were prescribed in 68.8% and antibiotics in 41% of cases. There seemed to be an increasing trend in the number of diagnosed and hospitalized cases over the years of the study. CONCLUSION: Patients with laboratory-confirmed influenza at our center had a high rate of hospitalization and mortality. A population based prospective surveillance study is needed to better estimate the burden of Influenza in Lebanon that would help formulate a policy on influenza control.

Prescriber Behavior in Clostridioides difficile Testing: A 3-Hospital Diagnostic Stewardship Intervention.

Computerized clinical decision support (CCDS) significantly reduced Clostridioides difficile testing at 3 hospitals; from 12.6 to 9.5, from 10.1 to 6.4, and from 14.0 to 9.6 average weekly tests per 1000 inpatient days. There were no related adverse events. Senior providers were more likely than interns or residents to follow CCDS.

NON-INVASIVE ASSESSMENT OF LIVER STEATOSIS AND FIBROSIS USING TRANSIENT ELASTOGRAPHY AND CONTROLLED ATTENUATION PARAMETER IN TYPE 2 DIABETES PATIENTS.

CONTEXT: Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. OBJECTIVE: To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. DESIGN: This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital "Pius Brinzeu" Timisoara. SUBJECTS AND METHODS: We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. RESULTS: The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). CONCLUSIONS: Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

Complications of Roux-en-Y gastric bypass.

INTRODUCTION: Bariatric surgery is a method of treating morbid obesity, which has been raising more and more interest in the past years. Among all types of intervention, the most frequently used is Roux-en-Y gastric bypass, an intervention both restrictive and malabsorptive, which leads to best results in weight loss. In Romania, bariatric surgery, and especially Roux-en-Y gastric bypass, is not widely practiced due to poor addressability of patients, both due to lack of information, and to poor recommendation from general practitioners and specialists in metabolic diseases. MATERIAL AND METHOD: The study group includes 14 patients aged between 18 and 65 years old, with BMI above 40 kg m2. The study aims to present the complications that occurred in this group of patients in which we performed Roux-en-Y gastric bypass in the Surgery Department of the Emergency City Hospital Timisoara. The surgery was performed by xifo-umbilical laparotomy technique. Subsequently, patients were followed postoperatively at 1 month, and then every 3 months, up to 2 years. RESULTS: The only complications we found were wound infections (7/14 - 50%) and incisional hernias (5/14 - 35.71%). CONCLUSIONS: We only found in our group only complications related to the postoperative wound that can be minimized by modifying the suturing technique of the abdominal wall. Gastric bypass should be performed despite all incriminated risks, providing a better lifestyle to obese patients.

Efficacy of oxycodone/paracetamol for patients with bone-cancer pain: a multicenter, randomized, double-blinded, placebo-controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Bone-cancer pain is a common and refractory cancer pain. Opioids, on their own, do not control this type of pain well enough, and co-analgesics are necessary. METHODS: Patients with bone metastasis-related pain at Numeric Rating Scale ≥4 were enrolled to this randomized placebo-controlled trial. They had also received morphine or transdermal fentanyl patches for at least 1 week. During the 3-day efficacy phase, patients received placebo or 1-3 tablets of oxycodone/paracetamol (5/325 mg), four times daily for 3 days. All patients kept a daily pain diary. The primary endpoint was the Pain Intensity Difference (PID). Secondary endpoints were cases of breakthrough pain and rescue morphine consumption. Additional analyses included the Short Form-6 Dimensions (SF-6D) quality-of-life scale and a general impression (GI) of patient satisfaction with treatment at the end of the phase. RESULTS AND DISCUSSION: Of the 246 patients in the intent-to-treat set, 89·4% completed the 3-day efficacy phase. PIDs were 0·9 and 0·3 in the oxycodone/paracetamol and placebo groups respectively, on day 1 (P < 0·001), and 1·5 and 0·3 respectively on day 3 (P < 0·001). Thirty-eight patients in the treatment group, and 58 in the placebo group, suffered breakthrough pain on day 3 (P < 0·001). The SF-6D score decreased to 21·2 ± 2·5 in the oxycodone/paracetamol group at the end of the phase (P = 0·001). In the oxycodone/paracetamol group, 67% rated GI as good, very good, or excellent. WHAT IS NEW AND CONCLUSION: Patients with bone-cancer pain, already on opioids, obtain clinically important, additional pain-control, with regular oxycodone/paracetamol dosing.

Postoperative morbidity and mortality after liver resection. Retrospective study on 133 patients.

INTRODUCTION: Hepatic resection had an impressive growth over time, both by broadening the range of its indications and the occurrence of changes and technical tricks in order to reduce postoperative mortality and morbidity. MATERIAL AND METHODS: This study is a retrospective study presenting an analysis of 133 patients hospitalized in the Department of Hepatic Surgery in City Hospital Timisoara, between January 2000 and November 2011, in which a surgical intervention was performed, either for a primary hepatic tumor (benign or malignant) or a secondary liver tumor. All cases were analyzed in terms of etiopathogenesis, preoperative and intraoperative investigations, indication and type of hepatectomy performed, the surgical technique used and postoperative evolution. RESULTS: The study group comprises 133 patients. From the whole group, 100 patients (75.19%) were diagnosed with primitive liver tumors, in 70 patients (70% of primary tumors) HCC occurring on a cirrhotic liver. Liver disease was secondary in 33 patients (24.81%), colorectal tumors being most commonly involved (19 patients). Of all liver resections, 21 (15.79%) were major hepatectomies. The remaining were minor hepatectomies, including a trisegmentectomy (V, VI, VII), 51 bisegmentectomies and 60 liver resections limited to one segment. Vascular clamping was used in 89 cases (66.92%), pedicular clamping in 65 patients (73.03%) and selective extraglissonian clamping in 24 patients (26.97%) respectively. Of the 33 patients with liver metastases, 12 (36.36%) received synchronous resections. The most common complication in our study group was postoperative liver failure, found in 45 patients (33.83%), being irreversible in one case (2.22%), followed by the death of the patient. In 34 patients (75.55%), hepatic failure was seen in cirrhotic patients and the other cases were patients with major hepatec-tomies. Hepatic failure occurred in 35 patients (77.78%) with vascular clamping, four of them after selective clamping. 31 of the patients (68.89%) with postoperative liver failure were transfused, 25 patients (55.55%) receiving more than 2 units of blood. Of all patients, 3 (2.25%) died postoperatively. CONCLUSIONS: Respecting the principles of liver surgery, hepatic resection can be performed, even in cirrhotic patients, with acceptable morbidity and minimal mortality. The most common complication after hepatic resection, in our study group, was postoperative liver failure, which was mostly reversible.

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis.

Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician. In this paper, we will review the latest evidence for the optimal treatment of P. aeruginosa sepsis caused by susceptible as well as multidrug-resistant strains including the difficult to treat pathogens. We will also discuss the mode of drug infusion, indications for combination therapy, along with the proper dosing and duration of treatment for various conditions with a brief discussion of the use of non-antimicrobial agents.

The Voice of the Patient: Patient Roles in Antibiotic Management at the Hospital-to-Home Transition.

OBJECTIVE: Our objective was to characterize tasks required for patient-performed antibiotic medication management (MM) at the hospital-to-home transition, as well as barriers to and strategies for patient-led antibiotic MM. Our overall goal was to understand patients' role in managing antibiotics at the hospital-to-home transition. METHODS: We performed a qualitative study including semistructured interviews with health care workers and contextual inquiry with patients discharged home on oral antibiotics. The setting was one academic medical center and one community hospital. Participants included 37 health care workers and 16 patients. We coded interview transcripts and notes from contextual inquiry and developed themes. RESULTS: We identified 6 themes involving barriers or strategies for antibiotic MM. We identified dissonance between participant descriptions of the ease of antibiotic MM at the hospital-to-home transition and their experience of barriers. Similarly, patients did not always recognize when they were experiencing side effects. Lack of access to follow-up care led to unnecessarily long antibiotic courses. Instructions about completing antibiotics were not routinely provided. However, patients typically did not question the need for the prescribed antibiotic. CONCLUSIONS: There are many opportunities to improve patient-led antibiotic MM at the hospital-to-home transition. Mismatches between patient perceptions and patient experiences around antibiotic MM at the hospital-to-home transition provide opportunities for health system improvement.

The influence of silicon substitution on the properties of spherical- and whisker-like biphasic α-calcium-phosphate/hydroxyapatite particles.

In this work, the influence of the morphology of hydroxyapatite particles on silicon substitution through hydrothermal synthesis performed under the same conditions was investigated. Spherical- and whisker-like hydroxyapatite particles were obtained starting from calcium-nitrate, sodium dihydrogen phosphate, disodium-ethylenediaminetetraacetic acid and urea (used only for the synthesis of whisker-like particles) dissolved in aqueous solutions. Silicon was introduced into the solution using tetraethylorthosilicate. X-ray diffraction, infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy and transmission electron microscopy indicate that silicon doping induce different phase compositions and bioactivity of spherical- and whisker-like hydroxyapatite particles obtained under the same hydrothermal conditions. Silicon-substituted, spherical hydroxyapatites particles showed greater phase transformation to silicon-substituted α- calcium-phosphate compared with whiskers-like hydroxyapatite particles synthesized with the same amount of added silicon. Metabolic activity assay performed with SaOs2 osteosarcoma cells showed better biocompatibility of annealed biphasic spherical-like particles compared with annealed whiskerlike particles while dried spherical-like particles induce high cytotoxicity effect.

Decolonization of Staphylococcus aureus.

Staphylococcus aureus infections are associated with increased morbidity, mortality, hospital stay, and health care costs. S aureus colonization has been shown to increase risk for invasive and noninvasive infections. Decolonization of S aureus has been evaluated in multiple patient settings as a possible strategy to decrease the risk of S aureus transmission and infection. In this article, we review the recent literature on S aureus decolonization in surgical patients, patients with recurrent skin and soft tissue infections, critically ill patients, hospitalized non-critically ill patients, dialysis patients, and nursing home residents to inform clinical practice.

A healthcare worker and patient-informed approach to oral antibiotic decision making during the hospital-to-home transition.

In a qualitative study of healthcare workers and patients discharged on oral antibiotics, we identified 5 barriers to antibiotic decision making at hospital discharge: clinician perceptions of patient expectations, diagnostic uncertainty, attending physician-led versus multidisciplinary team culture, not accounting for total antibiotic duration, and need for discharge prior to complete data.