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1.
PLoS Pathog ; 20(3): e1012038, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38489257

ABSTRACT

Ebola disease (EBOD) remains a significant and ongoing threat to African countries, characterized by a mortality rate of 25% to 90% in patients with high viral load and significant transmissibility. The most recent outbreak, reported in Uganda in September 2022, was declared officially over in January 2023. However, it was caused by the Sudan Ebola virus (SUDV), a culprit species not previously reported for a decade. Since its discovery in 1976, the management of EBOD has primarily relied on supportive care. Following the devastating outbreak in West Africa from 2014 to 2016 secondary to the Zaire Ebola virus (EBOV), where over 28,000 lives were lost, dedicated efforts to find effective therapeutic agents have resulted in considerable progress in treating and preventing disease secondary to EBOV. Notably, 2 monoclonal antibodies-Ebanga and a cocktail of monoclonal antibodies, called Inmazeb-received Food and Drug Administration (FDA) approval in 2020. Additionally, multiple vaccines have been approved for EBOD prevention by various regulatory bodies, with Ervebo, a recombinant vesicular stomatitis virus-vectored vaccine against EBOV being the first vaccine to receive approval by the FDA in 2019. This review covers the key signs and symptoms of EBOD, its modes of transmission, and the principles guiding supportive care. Furthermore, it explores recent advancements in treating and preventing EBOD, highlighting the unique properties of each therapeutic agent and the ongoing progress in discovering new treatments.


Subject(s)
Ebola Vaccines , Ebolavirus , Hemorrhagic Fever, Ebola , Viral Vaccines , Humans , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Antibodies, Viral , Ebolavirus/genetics , Antibodies, Monoclonal/therapeutic use , Uganda/epidemiology
2.
Clin Infect Dis ; 78(2): 248-258, 2024 02 17.
Article in English | MEDLINE | ID: mdl-37738153

ABSTRACT

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Humans , Acinetobacter baumannii/genetics , Carbapenems/pharmacology , Carbapenems/therapeutic use , Prospective Studies , Microbial Sensitivity Tests , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , beta-Lactamases/genetics , Bacterial Proteins/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
3.
Curr Opin Infect Dis ; 37(2): 105-111, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38037890

ABSTRACT

PURPOSE OF REVIEW: The aim of this review is to discuss the latest evidence of epidemiology, diagnostic methods, and treatment of necrotizing soft tissue infections (NSTIs) with a particular focus on necrotizing fasciitis (NF). RECENT FINDINGS: NSTIs have been historically referred to as NF but encompass a broader range of infections, with variable rates ranging from 0.86 to 32.64 per 100 000 person-years, influenced by factors such as climate and seasonal variations. They have diverse microbiological profiles categorized into different types based on the involved pathogens, including polymicrobial or monomicrobial infections caused by organisms such as group A streptococcus (GAS), Staphylococcus aureus , some Gram-negative pathogens, and filamentous fungi following trauma and natural disasters. Diagnosis relies on clinical symptoms and signs, laboratory markers, and imaging. However, the gold standard for diagnosis remains intraoperative tissue culture. Treatment involves repeated surgical debridement of necrotic tissues in addition to intravenous antibiotics. Adjuvant therapies with intravenous immunoglobulin (IVIG) and hyperbaric oxygen therapy (HBOT) might have a role. Soft tissue reconstruction may be necessary following surgery. SUMMARY: Prompt diagnosis and proper medical and surgical management of NSTI will improve outcomes.


Subject(s)
Fasciitis, Necrotizing , Soft Tissue Infections , Humans , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/epidemiology , Fasciitis, Necrotizing/therapy , Soft Tissue Infections/diagnosis , Soft Tissue Infections/epidemiology , Soft Tissue Infections/therapy , Anti-Bacterial Agents/therapeutic use , Combined Modality Therapy , Streptococcus pyogenes
4.
J Antimicrob Chemother ; 79(6): 1203-1217, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38629250

ABSTRACT

Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug-drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine). We highlight interactions with drugs used in children and new agents introduced for the treatment of haematological malignancies or graft versus host disease (midostaurin, ibrutinib, ruxolitinib and venetoclax). We also summarize the multiple interactions between oral and inhaled corticosteroids and triazole antifungals, and the strategies needed to optimize the therapeutic benefits of triazole antifungal therapy while minimizing potential harm to patients.


Subject(s)
Antifungal Agents , Drug Interactions , Triazoles , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacology , Triazoles/therapeutic use , Triazoles/administration & dosage , Mycoses/drug therapy , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use
5.
PLoS Pathog ; 18(12): e1011008, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36459501

ABSTRACT

[This corrects the article DOI: 10.1371/journal.ppat.1010768.].

6.
PLoS Pathog ; 18(9): e1010768, 2022 09.
Article in English | MEDLINE | ID: mdl-36136979

ABSTRACT

Monkeypox (MPX) has recently made international headlines for the rapid and simultaneous progression of the disease across the world. This review aims at summarizing the literature available as well as describing the evolution of the disease as it pertains to the cases today along with potential treatments and infection control strategies. To date, more than 76 countries have reported cases in more than 12,261 people. Before this, MPX was a rare zoonotic disease confined to endemic areas in Western and Central Africa with sporadic outbreaks namely in the United States, associated with the import of wild animals from Ghana. However, during the current outbreak, human-to-human transmission has become the primary mode of transmission, raising concerns for unaccounted community spread. Most of these patients did not travel to the endemic areas of Africa, suggesting possible previously underdetected community transmission. Observations from emergent cases have reported that the manifestations of the disease were sometimes atypical from what has been previously described. Young men who have sex with men seem to be the population most vulnerable to infection. Though the disease is currently perceived to be mild in its clinical course, questions that remain unclear and warrant further investigation include potential of humans harboring a genital reservoir of the virus and the possibility of airborne transmission, which has implications for infection control and health of the community at large.


Subject(s)
Mpox (monkeypox) , Sexual and Gender Minorities , Africa, Central , Animals , Homosexuality, Male , Humans , Male , Mpox (monkeypox)/epidemiology , Monkeypox virus
7.
Mycoses ; 67(7): e13762, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38951663

ABSTRACT

Infections are well-known complications in patients following traumatic injuries, frequently leading to high morbidity and mortality. In particular, trauma occurring in disaster settings, both natural and man-made, such as armed conflicts and explosives detonation, results in challenging medical conditions that impede the best management practices. The incidence of invasive fungal infections (IFI) is increasing in trauma patients who lack the typical risk factors like an immune compromised state or others. This narrative review will focus on IFI as a direct complication after natural disasters, wars, and man-made mass destruction with a summary of the available evidence about the epidemiology, clinical manifestations, risk factors, microbiology, and proper management. In this setting, the clinical manifestations of IFI may include skin and soft tissue infections, osteomyelitis, visceral infections, and pneumonia. IFI should be considered in the war inflicted patients who are exposed to unsterile environments or have wounds contaminated with soil and decaying organic matter.


Subject(s)
Invasive Fungal Infections , Humans , Invasive Fungal Infections/epidemiology , Natural Disasters , Risk Factors , Warfare , Antifungal Agents/therapeutic use , Incidence
8.
Clin Infect Dis ; 77(4): 499-509, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37154071

ABSTRACT

BACKGROUND: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. METHODS: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-ß-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. RESULTS: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. CONCLUSIONS: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , beta-Lactamases , Humans , Prospective Studies , beta-Lactamases/genetics , Escherichia coli/genetics , Bacterial Proteins/genetics , Carbapenem-Resistant Enterobacteriaceae/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests
9.
Curr Opin Infect Dis ; 36(2): 67-73, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36718912

ABSTRACT

PURPOSE OF REVIEW: The aim of this review is to discuss the latest evidence of the epidemiology, microbiology, risk factors, diagnosis and management of community-acquired skin and soft tissue infections (SSTIs) in people who inject drug (PWID). RECENT FINDINGS: SSTIs are common complications in PWID and a major cause of morbidity and mortality. Infections can range from uncomplicated cellulitis, to abscesses, deep tissue necrosis and necrotizing fasciitis. They are predominantly caused by Gram-positive pathogens in particular Staphylococcus aureus and Streptococcus species; however, toxin-producing organisms such as Clostridium botulism or Clostridium tetani should be considered. The pathogenesis of SSTI in the setting of intravenous drug use (IDU) is different from non-IDU related SSTI, and management often requires surgical interventions in addition to adjunctive antibiotics. Harm reduction strategies and education about safe practices should be implemented to prevent morbidity and mortality as well as healthcare burden of SSTI in PWID. SUMMARY: Prompt diagnosis and proper medical and surgical management of SSTI will improve outcomes in PWID.


Subject(s)
Community-Acquired Infections , Drug Users , Methicillin-Resistant Staphylococcus aureus , Skin Diseases, Infectious , Soft Tissue Infections , Substance Abuse, Intravenous , Humans , Soft Tissue Infections/etiology , Soft Tissue Infections/complications , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/epidemiology , Skin , Skin Diseases, Infectious/epidemiology , Skin Diseases, Infectious/etiology , Community-Acquired Infections/etiology , Community-Acquired Infections/complications
10.
Med Mycol ; 61(10)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37793805

ABSTRACT

The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment, and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as hematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions. As a collaborative effort between authors affiliated to the Infection Prevention and Control Working Group and the Fungal Infection Working Group of the International Society of Antimicrobial Chemotherapy (ISAC), we reviewed the English language literature and international guidance to describe the evidence behind the need for environmental monitoring for filamentous fungi as a quality assurance approach with an emphasis on required additional precautions during periods of construction. Many different clinical sampling approaches have been described for air, water, and surface sampling with significant variation in laboratory methodologies between reports. Importantly, there are no agreed-upon thresholds that correlate with an increase in the clinical risk of mould infections. We highlight important areas for future research to assure a safe environment for highly immunocompromized patients.


Mould infections have a high mortality in high-risk patients. Ventilation engineering significantly reduces the risk of acquiring such infections. Environmental sampling for moulds is carried out in many centers in addition to standard precautions. We review the literature on this subject.


Subject(s)
Aspergillosis , Hematopoietic Stem Cell Transplantation , Mycoses , Humans , Aspergillosis/drug therapy , Aspergillosis/veterinary , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/veterinary , Fungi/genetics , Mycoses/epidemiology , Mycoses/prevention & control , Mycoses/drug therapy , Mycoses/veterinary , Environmental Monitoring
11.
Curr Opin Infect Dis ; 35(6): 614-620, 2022 12 01.
Article in English | MEDLINE | ID: mdl-35942853

ABSTRACT

PURPOSE OF REVIEW: Antimicrobial overuse is a major health problem that contributes to antimicrobial resistance (AMR). Infections with Gram-negative bacilli (GNB) and multidrug-resistant organisms (MDRs) are associated with high morbidity and mortality, particularly in patients with underlying medical conditions. RECENT FINDINGS: Although many recent studies have been published about the novel antibiotics in treating infections including those due to MDR-GNB, the optimal duration of treatment (DOT) remains inconclusive. Recent observation has supported that short antibiotic therapy (SAT) decreases AMR and adverse effects. This narrative review provides an overview of the most recent published studies on the duration of therapy in the treatment of GNB infections, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), intra-abdominal infections (IAIs), bloodstream infections (BSIs) and urinary tract infections (UTIs), with a particular focus on MDR-GNB. SUMMARY: Studies showed different outcomes when comparing SAT to long antimicrobial therapy (LAT). No generalization can be made on all sites of infections and different GNBs. Further studies are needed to address the optimal DOT in MDR-GNB, as this group is underrepresented in recent studies.


Subject(s)
Cross Infection , Gram-Negative Bacterial Infections , Pneumonia, Ventilator-Associated , Humans , Drug Resistance, Multiple, Bacterial , Cross Infection/drug therapy , Pneumonia, Ventilator-Associated/drug therapy , Anti-Bacterial Agents , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy
12.
Curr Opin Infect Dis ; 35(2): 112-119, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34812745

ABSTRACT

PURPOSE OF REVIEW: Staphylococcus aureus is a pathogen incriminated in skin and soft tissue infections (SSTIs), with methicillin-resistant S. aureus (MRSA) becoming the predominant cause and representing a significant burden to the healthcare system. The last updated Infectious Diseases Society of America (IDSA) guidelines concerning MRSA infections and SSTIs management were published in 2011 and 2014, respectively. The UK updated guidelines for MRSA infection treatment were published in 2021. Older treatment options may be associated with toxicity and require frequent dosing. There is a paucity of recent reviews on the armamentarium of new agents for MRSA SSTIs treatment. RECENT FINDINGS: Since 2005, several new antibiotics received a fast-track approval by the Food and Drug Administration (FDA) for SSTI treatment. These drugs include delafloxacin, omadacycline, tedizolid, ceftaroline, dalbavancin, oritavancin and telavancin. In this manuscript, we will review the data that led to these new drugs approval and discuss their advantages and disadvantages in MRSA SSTIs management. SUMMARY: MRSA is a major cause of SSTIs. Several novel therapies covering MRSA were FDA-approved for SSTIs. However, the current IDSA guidelines for MRSA infection and SSTIs as well as the recently published UK guidelines on MRSA treatment only consider these drugs as alternative choices or do not mention them at all.


Subject(s)
Community-Acquired Infections , Methicillin-Resistant Staphylococcus aureus , Soft Tissue Infections , Staphylococcal Infections , Staphylococcal Skin Infections , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/drug therapy , Humans , Soft Tissue Infections/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcal Skin Infections/drug therapy , Staphylococcus aureus
13.
Semin Respir Crit Care Med ; 43(1): 46-59, 2022 02.
Article in English | MEDLINE | ID: mdl-35172358

ABSTRACT

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.


Subject(s)
Candidemia , Candidiasis, Invasive , Communicable Diseases , Antifungal Agents/therapeutic use , Candidemia/drug therapy , Candidiasis , Candidiasis, Invasive/diagnosis , Candidiasis, Invasive/drug therapy , Communicable Diseases/drug therapy , Critical Illness , Humans , Intensive Care Units
14.
Curr Opin Infect Dis ; 33(6): 464-473, 2020 12.
Article in English | MEDLINE | ID: mdl-33148986

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/isolation & purification , Antimicrobial Stewardship/methods , Cephalosporins/therapeutic use , Drug Resistance, Multiple, Bacterial/drug effects , Fluoroquinolones/therapeutic use , Humans , Phage Therapy/methods , beta-Lactamase Inhibitors/therapeutic use , beta-Lactams/therapeutic use , Cefiderocol
15.
Curr Opin Infect Dis ; 33(2): 146-154, 2020 04.
Article in English | MEDLINE | ID: mdl-32022742

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Gram-Negative Bacterial Infections/microbiology , Skin Diseases, Bacterial/drug therapy , Skin Diseases, Bacterial/microbiology , Soft Tissue Infections/drug therapy , Soft Tissue Infections/microbiology , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , Humans
16.
J Antimicrob Chemother ; 75(Suppl 2): ii20-ii32, 2020 12 06.
Article in English | MEDLINE | ID: mdl-33280046

ABSTRACT

BACKGROUND: Antimicrobial surveillance and antimicrobial stewardship (AMS) are essential pillars in the fight against antimicrobial resistance (AMR), but practical guidance on how surveillance data should be linked to AMS activities is lacking. This issue is particularly complex in the hospital setting due to structural heterogeneity of hospital facilities and services. The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions for linking surveillance data with AMS activities. METHODS: A scoping review of the literature was carried out addressing research questions on three areas: (i) AMS leadership and accountability; (ii) antimicrobial usage and AMS; (iii) AMR and AMS. Consensus on the target actions was reached through a RAND-modified Delphi process involving over 40 experts in different fields from 18 countries. RESULTS: Evidence was retrieved from 51 documents. Initially 38 targets were proposed, differentiated as essential or desirable according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for 32 targets. Following a second consultation, 27 targets were approved, 11 were deleted and 4 were suggested for rephrasing, leading to a final approved list of 34 target actions in the form of a practical checklist. CONCLUSIONS: This White Paper provides a pragmatic and flexible tool to guide the development of calibrated hospital-surveillance-based AMS interventions. The strength of this tool is that it is a comprehensive perspective that takes into account the hospital patient case-mix and the related epidemiology, which ultimately drives antimicrobial usage, and the feasibility in low-resource settings.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , Animals , Anti-Bacterial Agents/therapeutic use , Hospitals , Humans , Magnets , Policy
17.
BMC Infect Dis ; 20(1): 339, 2020 May 12.
Article in English | MEDLINE | ID: mdl-32397965

ABSTRACT

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.


Subject(s)
Coinfection/diagnosis , Coinfection/epidemiology , Influenza A Virus, H1N1 Subtype/genetics , Influenza B virus/genetics , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Pandemics , Adolescent , Adult , Aged , Antiviral Agents/therapeutic use , Child , Child, Preschool , Coinfection/complications , Coinfection/drug therapy , Female , Hospitalization , Humans , Infant , Infant, Newborn , Influenza A Virus, H1N1 Subtype/immunology , Influenza B virus/immunology , Influenza, Human/complications , Influenza, Human/drug therapy , Lebanon/epidemiology , Male , Middle Aged , Morbidity , Pneumonia/etiology , Retrospective Studies , Tertiary Care Centers , Young Adult
18.
Infection ; 47(2): 335, 2019 04.
Article in English | MEDLINE | ID: mdl-30617837

ABSTRACT

Unfortunately, the original version of this article contains mistakes. The names "Jean El-Cheikh" and Aline El Zakhem were spelled incorrectly.

19.
BMC Infect Dis ; 19(1): 293, 2019 Mar 29.
Article in English | MEDLINE | ID: mdl-30925909

ABSTRACT

BACKGROUND: The Lebanese Society of Infectious Diseases and Clinical Microbiology (LSIDCM) is involved in antimicrobial stewardship. In an attempt at guiding clinicians across Lebanon in regards to the proper use of antimicrobial agents, members of this society are in the process of preparing national guidelines for common infectious diseases, among which are the guidelines for empiric and targeted antimicrobial therapy of complicated intra-abdominal infections (cIAI). The aims of these guidelines are optimizing patient care based on evidence-based literature and local antimicrobial susceptibility data, together with limiting the inappropriate use of antimicrobials thus decreasing the emergence of antimicrobial resistance (AMR) and curtailing on other adverse outcomes. METHODS: Recommendations in these guidelines are adapted from other international guidelines but modeled based on locally derived susceptibility data and on the availability of pharmaceutical and other resources. RESULTS: These guidelines propose antimicrobial therapy of cIAI in adults based on risk factors, site of acquisition of infection, and clinical severity of illness. We recommend using antibiotic therapy targeting third-generation cephalosporin (3GC)-resistant gram negative organisms, with carbapenem sparing as much as possible, for community-acquired infections when the following risk factors exist: prior (within 90 days) exposure to antibiotics, immunocompromised state, recent history of hospitalization or of surgery and invasive procedure all within the preceding 90 days. We also recommend antimicrobial de-escalation strategy after culture results. Prompt and adequate antimicrobial therapy for cIAI reduces morbidity and mortality; however, the duration of therapy should be limited to no more than 4 days when adequate source control is achieved and the patient is clinically stable. The management of acute pancreatitis is conservative, with a role for antibiotic therapy only in specific situations and after microbiological diagnosis. The use of broad-spectrum antimicrobial agents including systemic antifungals and newly approved antibiotics is preferably restricted to infectious diseases specialists. CONCLUSION: These guidelines represent a major step towards initiating a Lebanese national antimicrobial stewardship program. The LSIDCM emphasizes on development of a national AMR surveillance network, in addition to a national antibiogram for cIAI stratified based on the setting (community, hospital, unit-based) that should be frequently updated.


Subject(s)
Anti-Infective Agents/therapeutic use , Drug Resistance, Microbial , Intraabdominal Infections/drug therapy , Adult , Community-Acquired Infections/prevention & control , Humans , Immunocompromised Host , Intraabdominal Infections/microbiology , Lebanon , Microbial Sensitivity Tests , Pancreatitis/drug therapy , Pancreatitis/microbiology , Time Factors
20.
Mycoses ; 62(4): 310-319, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30426598

ABSTRACT

BACKGROUND: The reliability of diagnostic criteria for invasive fungal diseases (IFD) developed for severely immunocompromised patients is questionable in critically ill adult patients in intensive care units (ICU). OBJECTIVES: To develop a standard set of definitions for IFD in critically ill adult patients in ICU. METHODS: Based on a systematic literature review, a list of potential definitions to be applied to ICU patients will be developed by the ESCMID Study Group for Infections in Critically Ill Patients (ESGCIP) and the ESCMID Fungal Infection Study Group (EFISG) chairpersons. The proposed definitions will be evaluated by a panel of 30 experts using the RAND/UCLA appropriateness methods. The panel will rank each of the proposed definitions on a 1-9 scale trough a dedicated questionnaire, in two rounds: one remote and one face-to-face. Based on their median rank and the level of agreement across panel members, selected definitions will be organised in a main consensus document and in an executive summary. The executive summary will be made available online for public comments. CONCLUSIONS: The present consensus project will seek to provide standard definitions for IFD in critically ill adult patients in ICU, with the ultimate aims of improving their clinical outcome and facilitating the comparison and generalizability of research findings.


Subject(s)
Critical Illness , Intensive Care Units , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/pathology , Terminology as Topic , Consensus , Humans
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