Diagnosis and Management of Invasive Candida Infections in Critically Ill Patients.

Invasive candidiasis (IC) has become a serious problem in the intensive care unit patients with an attributable mortality rate that can reach up to 51%. Multiple global surveillance studies have shown an increasing incidence of candidemia. Despite their limited sensitivity (21-71%), cultures remain the gold standard for the diagnosis of IC associated with candidemia. Many adjunct laboratory tests exist to support or rule out the diagnosis, each with its indications and limitations, including procalcitonin, 1,3-ß-D-glucan, mannan and anti-mannan antibodies, and Candida albicans germ tube antibody. In addition, polymerase chain reaction-based methods could expedite species identification in positive blood cultures, helping in guiding early empirical antifungal therapy. The management of IC in critically ill patients can be classified into prophylactic, preemptive, empiric, and directed/targeted therapy of a documented infection. There is no consensus concerning the benefit of prophylactic therapy in critically ill patients. While early initiation of appropriate therapy in confirmed IC is an important determinant of survival, the selection of candidates and drug of choice for empirical systemic antifungal therapy is more controversial. The choice of antifungal agents is determined by many factors, including the host, the site of infection, the species of the isolated Candida, and its susceptibility profile. Echinocandins are considered initial first-line therapy agents. Due to the conflicting results of the various studies on the benefit of preemptive therapy for critically ill patients and the lack of robust evidence, the Infectious Diseases Society of America (IDSA) omitted this category from its updated guidelines and the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) do not recommend it.

Bacterial bloodstream infections and patterns of resistance in patients with haematological malignancies at a tertiary centre in Lebanon over 10 years.

OBJECTIVES: Bacterial bloodstream infections (BSIs) with resistant pathogens in patients with haematological malignancies are rising due to increased use of novel chemotherapeutic agents and prophylactic antibiotics. Our goal was to understand the epidemiology and resistance patterns of bacterial pathogens in patients with haematological malignancies to help tailor empirical antibiotics and to limit resistance. METHODS: This was a retrospective chart review looking at bacterial BSI episodes between 2007-2017 in patients previously diagnosed with haematological malignancy at a tertiary-care centre in Lebanon. RESULTS: Among 165 hospitalised patients with haematological malignancy and bacterial BSI over 10 years, Gram-negative bacteria (GNB) caused 65.0% of all episodes, with the most common pathogens being Escherichia coli (45.6%), 79.6% of which were ESBL-producers, Pseudomonas aeruginosa (7.5%) and Acinetobacter baumannii (4.0%). The majority of the organisms (61.0%) were multidrug-resistant (MDR), with ANC < 100 neutrophils/µL (OR = 0.12, 95% CI 0.03-0.54) identified as an independent marker for increased multidrug resistance. The risk factors associated with increased mortality included recent use of amikacin (p<0.001) and infections with organisms resistant to amikacin (p<0.001) or ciprofloxacin (p=0.04). Our results reflect a persistent pattern of Gram-negative predominance with E. coli remaining the most common isolated pathogen in bacterial BSIs in patients with haematological malignancies. The relative frequency of GNB to Gram-positive bacteria remains similar to our data from 2007. CONCLUSION: The persistent divergence between worldwide data and the results observed in our centre and the increasing rates of MDR pathogens emphasise the importance of tailoring empirical antimicrobial therapy according to the centre's epidemiology.

Predominance of Candida Glabrata among Non-albicans Candida Species in a 16-Year Study of Candidemia at a Tertiary Care Center in Lebanon.

BACKGROUND: Candidemia is associated with a high mortality rate, and its incidence is increasing worldwide with a rise in non-albicans candidemia (NAC). Epidemiologic data from Arab countries are scarce and there are no data from Lebanon; Methods: This is a single-center retrospective chart review of patients with candidemia in a tertiary care center in Lebanon from 2004 to 2019. We extracted data on patient characteristics, isolated Candida species antifungal susceptibility, management and outcomes; Results: We included 170 cases of candidemia. NAC was more common than albicans candidemia (64.7% vs. 35.3%). C. glabrata was the most common non-albicans species (37 isolates) followed by C. tropicalis (14). Recent use of antifungals was a risk factor for NAC (OR = 2.8, p = 0.01), while the presence of a central venous catheter was protective (OR = 0.41, p = 0.02). Fluconazole resistance was 12.5% in C. albicans and 21.5% in non-albicans spp. Mortality at 30 days was 55.5%, with no difference between NAC and albicans candidemia. It was higher in older and critically ill patients but lower in patients whose central venous catheter was removed after detecting fungemia; Conclusions: Candidemia is associated with high mortality in Lebanon, with a predominance of NAC and high prevalence of C. glabrata.

Gram-Negative Skin and Soft Tissue Infections.

Skin and soft tissue infections (SSTIs) frequently are encountered in clinical practice, and gram-negative bacilli (GNB) constitute an underrated portion of their etiology. The rate of GNB-causing SSTIs is increasing, especially with the rise in antimicrobial resistance. Although the diagnosis of SSTIs mostly is clinical, rapid diagnostic modalities can shorten the time to initiating proper therapy and improving outcomes. Novel antibiotics are active against GNB SSTIs and can be of great value in the management. This review provides an overview of the role of GNB in SSTIs and summarizes their epidemiology, risk factors, outcome, and clinical management.

Current choices of antibiotic treatment for Pseudomonas aeruginosa infections.

PURPOSE OF REVIEW: Pseudomonas aeruginosa is one of the most feared nosocomial pathogens. Treatment of P. aeruginosa infections is challenging because of the limited choices of antibiotics and the emergent resistance of the pathogen. The present review aims at addressing the management of P. aeruginosa infections and highlighting the novel antibiotics that show a future promising role. RECENT FINDINGS: Novel fluoroquinolones have been recently introduced and show favorable activity. New combinations of ß-lactams/ß-lactamase inhibitors have been studied in various indications of infections because of P. aeruginosa. Cefiderocol, a new cephalosporin, shows very promising results against P. aeruginosa. Currently, combination therapy is only recommended in limited scenarios. Extended-infusion of ß-lactams exhibit clinical benefit. Bacteriophage therapy is a growing field of interest and may have an impactful effect on the treatment of resistant P. aeruginosa. SUMMARY: Factors that guide clinical decisions for empiric and directed P. aeruginosa therapy include the epidemiology, the patient's risk factors, the site of infection, and the available treatment options. Conventional antipseudomonal antibiotics have been used successfully for a long time, but the increase in worldwide resistance necessitates the need for newer agents. Antimicrobial stewardship is essential to preserve the new drugs and prevent future development of resistance.

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.

Epidemiology and burden of invasive fungal infections in the countries of the Arab League.

The burden of invasive fungal infections is alarming worldwide. The aim of this paper is to review the published literature and evaluate the knowledge gap pertaining to studies on invasive fungal infections in the countries of the Arab League. Few countries from this region have published reports. The most commonly studied invasive fungal infections is invasive candidiasis. Candida albicans remains overall the most common causative pathogen (33.8-60%), however, non-albicans Candida species are increasing. Antifungal susceptibility testing is non-standardized across the published studies. Data on aspergillosis and other fungal infections is scarce. This sheds light on the need for standardized surveillance in the region encompassing more countries of the Arab League to guide diagnostic approach and empiric therapy.