Current Opinion in Infectious Diseases最新文献

Purpose of review: To provide a brief overview of drugs in Phase II and III of development for the treatment of acute bacterial skin and skin structure infections (ABSSSI), offering insights into potential customized treatment options.

Recent findings: Several drugs are currently in advanced stages of evaluation for the treatment of ABSSSI, and numerous molecules are entering in the early development phases. Notably, many of these drugs exhibit unique mechanisms of action and interesting antimicrobial spectrum.

Summary: Tailoring antibiotic therapy based on patient characteristics, likely pathogens, type, site and severity of ABSSSI is crucial. Given the inherent limitations of available treatments, the development of novel agents is a pivotal avenue. Such advancements hold promise for enhancing treatment efficacy and simplifying drug selection for ABSSSI in everyday clinical practice.

Purpose of review: The early recognition of acute bacterial skin infections (ABSIs) and their swift and adequate care are the major determinants of success. The features that can hamper or delay surgical and medical management can lead to 'difficult-to-treat' ABSIs.

Recent findings: Delayed diagnosis and belated management are the key obstacles to be overcome. Clinicians should be careful about underestimating the severity of ABSIs and overlooking comorbidities, especially immunosuppression. Many conditions can lead to delayed source control, including a misdiagnosis, interhospital transfers, delayed re-exploration, or extensive injuries. Difficult therapeutic issues can occur, including rapidly destructive infections from highly pathogenic microorganisms (Group-A-streptococci, Vibrio spp., Clostridium spp. and Staphylococcus aureus ) or inadequate antibiotic therapy resulting from multidrug-resistant bacteria. Impaired pharmacokinetic capacities of antibiotic agents should also be considered as a source of clinical failure due to insufficient antimicrobial activity at the site of infection.

Summary: Microbiological samples should be used for guiding antimicrobial therapy. Risk factors for multidrug-resistant bacteria should be considered, including local epidemiology and comorbidities. The optimization of antibiotic therapy should be achieved. Optimized care should be achieved through multidisciplinary management involving professionals with sufficient and appropriate training.

Purpose of review: There are aspects of skin and soft tissue infections (SSTIs) that remain unresolved, such as current numbers, classification criteria, how best to define severity and predict the outcome, what diagnostic tests to perform, what new treatment options are available, or what the duration of antibiotic treatment should be. We have reviewed the literature over the last 18 months to clarify these issues and provide our opinion.

Recent findings: SSTIs are common and among the top 10 most frequent infections worldwide. They represent a burden on the healthcare system and have a major impact on the quality of life of patients. Regarding classification, the Infectious Diseases Society of America (IDSA) provides a practical guide that distinguishes between uncomplicated and complicated infections, acute and chronic wound infections, and necrotising and nonnecrotizing infections based on skin extension and tissue necrosis. With new microbiological and imaging diagnostic techniques, SSTIs can now be better diagnosed. New PCR techniques are available, and mass spectrometry can be applied to samples collected in liquid transport media. Moreover, new treatment methods such as photodynamic therapy, reactive oxygen, and phages are emerging. SSTI patients can be treated with shorter antibiotic courses if they receive an active drug with good tissue penetration. Antibiotic treatment in necrotizing infections can be shortened to 48 h after the last debridement.

Summary: SSTIs remain a challenge regarding rapid and accurate diagnosis and clinical management.

Purpose of review: This review highlights the epidemiology of Pneumocystis jirovecii pneumonia in solid organ transplant recipients, advancements in the diagnostic landscape, and updates in treatment and prevention.

Recent findings: The increasing use of immune-depleting agents in the context of solid organ transplantation has given rise to P. jirovecii pneumonia in this population. The use of prophylaxis has dramatically reduced risk of infection; however, late-onset infections occur after cessation of prophylaxis and in the setting of lymphopenia, advancing patient age, acute allograft rejection, and cytomegalovirus infection. Diagnosis requires respiratory specimens, with PCR detection of Pneumocystis replacing traditional staining methods. Quantitative PCR may be a useful adjunct to differentiate between infection and colonization. Metagenomic next-generation sequencing is gaining attention as a noninvasive diagnostic tool. Trimethoprim-sulfamethoxazole remains the drug of choice for treatment and prevention of Pneumocystis pneumonia. Novel antifungal agents are under investigation.

Summary: P. jirovecii is a fungal opportunistic pathogen that remains a cause of significant morbidity and mortality in solid organ transplant recipients. Early detection and timely treatment remain the pillars of management.

Purpose of review: The purpose of this review is to briefly summarize the challenges associated with the treatment of pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB), discuss its carbapenem-resistance, and review the literature supporting the current treatment paradigm and therapeutic options.

Recent findings: In a multicenter, randomized, and controlled trial the novel β-lactam-β-lactamase inhibitor sulbactam-durlobactam was compared to colistin, both in addition to imipenem-cilastatin. The drug met the prespecified criteria for noninferiority for 28-day all-cause mortality while demonstrating higher clinical cure rates in the treatment of CRAB pneumonia. In an international, randomized, double-blind, placebo controlled trial colistin monotherapy was compared to colistin combined with meropenem. In this trial, combination therapy was not superior to monotherapy in the treatment of drug-resistant gram-negative organisms including CRAB pneumonia.

Summary: CRAB pneumonia is a preeminent public health threat without an agreed upon first line treatment strategy. Historically, there have been drawbacks to available treatment modalities without a clear consensus on the first-line treatment regimen. CRAB pneumonia is a top priority for the continued development of antimicrobials, adjuvant therapies and refinement of current treatment strategies.

Purpose of review: Skin and soft tissue infections (SSTI) in solid organ transplant (SOT) recipients may be a great challenge for clinicians caring for SOT due to the involvement of both common and opportunistic pathogens associated with a blunted immune response. The purpose of this review is to outline current literature and describe open issues on the management of SSTI in this special population.

Recent findings: Clinical presentation in SOT recipients can manifest as isolated skin lesions after primary inoculation or be the sign of a disseminated infection. Tissue samples for microscopy and histopathology are crucial to making an accurate diagnosis given the nonspecific and heterogeneous appearance of skin lesions. Multidisciplinary teams are required for a comprehensive diagnosis and management.

Summary: SSTI are frequent contributors to morbidity and mortality in SOT. Specific research focused on the clinical presentation, risk factors and management in this special population is needed.

Purpose of review: This review covers updated perspectives on different aspects of pneumococcal community-acquired pneumonia (pCAP), including the epidemiology, clinical presentation, risk factors, antibiotic treatment, and existing preventive strategies in older adults.

Recent findings: pCAP remains the most prevalent condition among lower respiratory tract infections in the older adults according to Global Burden of Diseases 2019. Older adults can display atypical symptoms such as confusion, general clinical deterioration, new onset of and exacerbation of underlying illness that might trigger clinical suspicion of pCAP. Older adults with pCAP often experience increased disease severity and a higher risk of pulmonary complications compared with younger individuals, owing to age-related changes in immunity and a higher prevalence of comorbidities. Vaccination stands fundamental for prevention, emphasizing the need for effective immunization strategies, specifically tailored for older adults. There is a pressing need to reinforce efforts aimed at boosting pneumococcal vaccination rates.

Summary: Despite a high morbidity and mortality, the burden of pCAP, in particular hospital admission and occurrence of invasive infections, among the elderly population is not sufficiently documented. This review findings emphasize the substantial burden of pCAP in this vulnerable population, driven by factors such as advancing age and underlying comorbidities. The emergence of antibiotic-resistant pneumococcal strains further complicates treatment decisions and highlights the importance of tailored approaches for managing pCAP in older adults.

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.

Purpose of review: To highlight the respiratory syncytial virus (RSV) disease burden and the current developments and challenges in RSV prevention for older adults ≥60 years through analysis of RSV epidemiology and the effectiveness of emerging vaccines.

Recent findings: In industrialized countries, RSV incidence rates and hospitalization rates among older adults are estimated to be 600.7 cases per 100 000 person-years and 157 hospitalizations per 100 000 person-years, respectively. Yet, accurately determining RSV morbidity and mortality in older adults is challenging, thus resulting in substantially under-estimating the disease burden. The in-hospital fatality rates vary substantially with age and geographies, and can be as high as 9.1% in developing countries. Two promising RSV vaccines for the elderly have been approved, demonstrating efficacies of up to 94.1%, signifying considerable advancement in RSV prevention. However, concerns over potential side effects remain.

Summary: RSV is associated with a significant burden in older adults. While the landscape of RSV prevention in older adults is promising with the licensure of vaccines from two companies, current trial data underscore the need for additional studies. Addressing the real-world effectiveness of these vaccines, understanding potential rare side effects, and ensuring broad inclusivity in future trials are crucial steps to maximize their potential benefits.

Purpose of review: Early detection and treatment of human papillomavirus (HPV)-related anal dysplasia in some high-risk groups can help anal cancer prevention, but new tools to improve diagnostic and risk assessment are needed. Here, we aim to discuss the evidence on the role of the microbiome as a potential biomarker for anal high-grade squamous intraepithelial lesions (HSILs) in people with HIV (PWH).

Recent findings: This review covers relevant studies on the links between the microbiome and HPV infection, cervical dysplasia/cancer, and anal HPV disease. It focuses on anal samples and precancerous lesions.

Summary: The review highlights the promising potential of the anal microbiome as a novel biomarker for precancerous lesions in people with HIV, while also discussing limitations and future research needs.