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.

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.

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.

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.

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.

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.

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.

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.

Infection surveillance and prevention strategies to detect and prevent postaccess breast tissue expander infections.

No standardized surveillance criteria exist for surgical site infection after breast tissue expander (BTE) access. This report provides a framework for defining postaccess BTE infections and identifies contributing factors to infection during the expansion period. Implementing infection prevention guidelines for BTE access may reduce postaccess BTE infections.

Molecular Epidemiology of Ceftriaxone Non-Susceptible Enterobacterales Isolates in an Academic Medical Center in the United States.

BACKGROUND: Knowledge of whether Enterobacterales are not susceptible to ceftriaxone without understanding the underlying resistance mechanisms may not be sufficient to direct appropriate treatment decisions. As an example, extended-spectrum ß-lactamase (ESBL)-producing organisms almost uniformly display non-susceptibility to ceftriaxone. Regardless of susceptibility to piperacillin-tazobactam or cefepime, carbapenem antibiotics are the treatment of choice for invasive infections. No such guidance exists for ceftriaxone non-susceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales. METHODS: All consecutive Escherichia coli, Klebsiellapneumoniae, Klebsiella oxytoca, or Proteus mirabilis clinical isolates with ceftriaxone MICs of ≥2 mcg/mL from unique patients at a United States hospital over an 8-month period were evaluated for ß-lactamase genes using a DNA microarray-based assay. RESULTS: Of 1929 isolates, 482 (25%) had ceftriaxone MICs of ≥2 mcg/mL and were not resistant to any carbapenem antibiotics. Of the 482 isolates, ESBL (blaCTX-M, blaSHV, blaTEM) and/or plasmid-mediated ampC (p-ampC) genes were identified in 376 (78%). ESBL genes were identified in 310 (82.4%), p-ampC genes in 2 (0.5%), and both ESBL and p-ampC genes in 64 (17.0%) of the 376 organisms. There were 211 (56%), 120 (32%), 41 (11%), and 4 (1%) isolates with 1, 2, 3, or 4 or more ESBL or p-ampC genes. The most common ESBL genes were of the blaCTX-M-1 group (includes blaCTX-M-15) and the most common p-ampC gene was the blaCMY-2. CONCLUSIONS: There is considerable diversity in the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.

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.

Epidemiology of common resistant bacterial pathogens in the countries of the Arab League.

No uniformly organised collection of data regarding antimicrobial resistance has occurred in the countries of the Arab League. 19 countries of the Arab League have published data for antimicrobial susceptibility for the WHO priority organisms, and seven of 14 of these organisms are included in this Review (Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa, Acinetobacter baumannii, Salmonella spp, Staphylococcus aureus, and Streptococcus pneumoniae). Although E coli and Klebsiella spp resistance to third-generation cephalosporins is common in all countries, with prevalence reaching more than 50% in Egypt and Syria, carbapenem resistance is emerging, albeit with a prevalence of less than 10%. Conversely, a large amount of carbapenem resistance has been reported for P aeruginosa and A baumannii across the Arab League, reaching 50% and 88% of isolates in some countries. As for Salmonella spp, the prevalence of fluoroquinolone resistance has exceeded 30% in several areas. With regards to the Gram-positive pathogens, the prevalence of meticillin resistance in S aureus is reported to be between 20% and 30% in most countries, but exceeds 60% in Egypt and Iraq. The prevalence of penicillin non-susceptibility among pneumococci has reached more than 20% in Algeria, Egypt, Morocco, Saudi Arabia, and Tunisia. These findings highlight the need for structured national plans in the region to target infection prevention and antimicrobial stewardship.

HACEK endocarditis: a review.

INTRODUCTION: The HACEK group, referring to Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, is a rare cause of infective endocarditis (IE). It causes the majority of Gram-negative endocarditis cases and has an excellent prognosis and simple management if properly identified. However, delay in diagnosis and associated complications can render the infection fatal. AREAS COVERED: Over the past few decades, there have been tremendous advancements in understanding the manifestations and progression of HACEK endocarditis (HE). This review tackles the epidemiology of HE, the microbiological characteristics of each organism in the HACEK group, the methods used to diagnose HE, the clinical manifestations, complications, and mortality of patients with HE, as well as the recommended treatment and preventive methods. Expert Commentary: The lack of robust randomized controlled trials in diagnosis and treatment of HE makes it difficult to determine the optimal management of such infections. Nevertheless, advancements in culturing methods have shown progress in isolating and identifying these fastidious organisms. Positive blood cultures for any of the HACEK organisms in the setting of no definite focus of infection is highly suggestive of HE. In such cases, treatment with ceftriaxone or a fluoroquinolone, even without obtaining antibiotic susceptibilities, should be initiated. Moreover, the decision to proceed with surgical intervention should be individualized. As is the case for other IE, HE requires the collaboration of a multidisciplinary team consisting of the infectious disease specialist, cardiologist, cardiothoracic surgeon, and the microbiologist.