Current challenges in acute bacterial skin infection management.

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.

How to manage skin and soft-tissue infections in the emergency department.

PURPOSE OF REVIEW: Our purpose is to review the state-of-the-art on the management of skin and soft tissue infections (SSTI) in emergency departments (ED).Although the information is scarce, SSTI may account for 3-30% of all cases presenting to an ED, of which 25-40% require hospital admission.SSTI include very different entities in aetiology, location, pathogenesis, extension, and severity. Therefore, no single management can be applied to them all. A simple approach is to classify them as non-purulent, purulent, and necrotising, to which a severity scale based on their systemic repercussions (mild, moderate, and severe) must be added.The initial approach to many SSTIs often requires no other means than anamnesis and physical examination, but imaging tests are an indispensable complement in many other circumstances (ultrasound, computerized tomography, magnetic resonance imaging…). In our opinion, an attempt at etiological filiation should be made in severe cases or where there is suspicion of a causality other than the usual one, with tests based not only on cultures of the local lesion but also molecular tests and blood cultures. RECENT FINDINGS: Recent contributions of interest include the value of bedside ultrasound and the potential usefulness of biomarkers such as thrombomodulin to differentiate in early stages the presence of necrotising lesions not yet explicit.New antimicrobials will allow the treatment of many of these infections, including severe ones, with oral drugs with good bioavailability and for shorter periods. SUMMARY: The ED has an essential role in managing SSTIs, in their classification, in decisions on when and where to administer antimicrobial treatment, and in the rapid convening of multidisciplinary teams that can deal with the most complex situations.

How to treat severe Acinetobacter baumannii infections.

PURPOSE OF REVIEW: To update the management of severe Acinetobacter baumannii infections (ABI), particularly those caused by multi-resistant isolates. RECENT FINDINGS: The in vitro activity of the various antimicrobial agents potentially helpful in treating ABI is highly variable and has progressively decreased for many of them, limiting current therapeutic options. The combination of more than one drug is still advisable in most circumstances. Ideally, two active first-line drugs should be used. Alternatively, a first-line and a second-line drug and, if this is not possible, two or more second-line drugs in combination. The emergence of new agents such as Cefiderocol, the combination of Sulbactam and Durlobactam, and the new Tetracyclines offer therapeutic options that need to be supported by clinical evidence. SUMMARY: The apparent limitations in treating infections caused by this bacterium, the rapid development of resistance, and the serious underlying situation in most cases invite the search for alternatives to antibiotic treatment, the most promising of which seems to be bacteriophage therapy.

Current international and national guidelines for managing skin and soft tissue infections.

PURPOSE OF REVIEW: Skin and soft tissue infections account for a significant percentage of both community and nosocomial infections. Several nosological entities are included in this concept. However, there is a very scarce body of doctrine for their treatment based on randomised trials. Therefore, we considered it necessary to review current treatment guidelines to bring new recommendations and improvements to our colleagues. In this review of recent literature, we identified updated guidelines in this area by searching the databases PubMed, evidence-based medicine online, York University reviewers group, Cochrane, MBE-Trip and Sumsearch using the terms: soft tissue infection, therapy, guideline. RECENT FINDINGS: Developments focus on using new antimicrobials and on the prescription of shorter antibiotic treatment courses. SUMMARY: With the development of new drugs and the current evidence of their use, there is a need to refine the appropriate drug's decision-making. Drugs with a long half-life, which allows weekly administration, can reduce hospital admission and length of stay with fewer healthcare resources. Shorter courses of antibiotics are recommended. The role of stewardship programmes will continue to expand. The surgical indication and its value are evident in many patients. Therefore, management should rely on a collaborative group with experience in this disease.

Controversies over the management of infections caused by Amp-C- and ESBL-producing Enterobacterales : what questions remain for future studies?

PURPOSE OF REVIEW: The continuous rise in infections caused by third-generation cephalosporin-resistant Enterobacterales (e.g. extended-spectrum beta-lactamase- or AmpC-producing Enterobacterales ) is a major health concern. Carbapenems are regarded as the antibiotics of choice for the treatment of these infections. However, their indiscriminant use is not without consequences, and has contributed to the emergence of carbapenem-resistant Enterobacterales .In this review, we discuss the available evidence supporting the use of other betalactams, nonbetalactams and the new betalactams/beta-lactamase inhibitors (BLA/BLI) to treat these infections. We also analyze unresolved issues in this field. RECENT FINDINGS: Piperacillin tazobactam (PTZ) was classically recommended as a carbapenem-sparing agent. However, data have emerged against its use and it is now a controversial recommendation. IDSA, European and British guidelines reject the empirical use of PTZ for these pathogens, reserving its use for rare clinical situations.Other issues that continue to generate debate are the use of extended infusion (3 h) PTZ, the use of older antibiotics, a shortened course of carbapenems and reserving the new BLA/BLI for these infections. SUMMARY: New treatment strategies should be based on clinical evidence, local epidemiology and the microbiological activity of these drugs.

The eternal dilemma of antitoxin antibiotics for skin and soft tissue infection.

PURPOSE OF REVIEW: In standard clinical practice, combined antibiotic treatment is used to treat severe skin and soft tissue infections (SSTIs), whereby one of the drugs is usually a protein synthesis inhibitor antibiotic. However, evidence for this practice is only based on data from 'in vitro' studies, animal models and case reports. There are no randomized controlled trials. In the light of several new drugs marketed for the treatment of these infections, there is a need to revise the state of the art. RECENT FINDINGS: New reviews and systematic appraisals of the literature exist on the use of protein synthesis inhibitor antibiotics to treat severe SSTI. Several 'in vitro' studies have assessed the efficacy of some of the new drugs. SUMMARY: Combination therapy, including an adjuvant protein synthesis inhibitor antibiotic for toxin suppression, should be used both in patients with severe SSTI and in those with moderate infection and risk factors for methicillin-resistant positive- or Panton-Valentine leukocidin positive-Staphylococcus aureus infection.

Gram-negative endocarditis: disease presentation, diagnosis and treatment.

PURPOSE OF REVIEW: Gram-negative bacilli (GNB) cause between 1% and 10% of infective endocarditis (IE). Most episodes are caused by microorganisms of the Haemophilus spp., Aggregatibacter spp. Cardiobacterium spp., Eikenella spp., and Kingella spp (HACEK) group. The frequency of IE caused by non-HACEK (GNB-IE) has increased in recent years. Uncertainties persist regarding its best medical treatment and the appropriateness and timing of surgical treatment. In addition, there are new drugs with activity against multiresistant microorganisms, of which there is little experience in this disease. We review this topic by answering the most frequently asked questions that arise among our colleagues. RECENT FINDINGS: HACEK microorganisms cause 1.5-2% of IE with only a 2% mortality. In contrast, non-HACEK GNB-IE accounts for 2.5-3% of all IE cases and is associated with nosocomial acquisition, advanced age, solid organ transplantation and 20-30% mortality. Drug addiction is important in areas with epidemic opioid abuse. SUMMARY: The frequency of IE caused by GNB has been modified in recent years. HACEK episodes are no longer treated with ampicillin and aminoglycosides. In non-HACEK GNB-IE, combination therapy with a beta-lactam and a quinolone or aminoglycoside is recommended. The surgical indication and its value are evident in many patients. Management should rely on a collaborative group with experience in this disease.

Risk stratification for multidrug-resistant Gram-negative infections in ICU patients.

PURPOSE OF REVIEW: Antimicrobial resistance among Gram-negative microorganisms has alarmingly increased in the past 10 years worldwide. Infections caused by these microorganisms are difficult to treat, especially in critically ill patients.The present review examines how to accurately predict which patients carry a greater risk of colonization or infection on which to base the timely choice of an effective empirical antibiotic treatment regimen and avoid antibiotic overuse. RECENT FINDINGS: There are many risk factors for acquiring one of many multidrug-resistant Gram-negative microorganisms (MDR-GN); however, scores anticipating colonization, infection among those colonized, or mortality among those infected have a variable accuracy. Accuracy of scores anticipating colonization is low. Scores predicting infections among colonized patients are, in general, better, and ICU patients infected with MDR-GN have a worse prognosis than those infected by non-resistant microorganisms. Scores are, in general, better at excluding patients. SUMMARY: Despite these limitations, scores continue to gain popularity including those by Giannella, Tumbarello, Johnson, or the scores INCREMENT carbapenem-producing Enterobacteriaceae score, Cano, Tartof, or CarbaSCORE.

The role of tedizolid in skin and soft tissue infections.

PURPOSE OF REVIEW: Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, including MRSA isolates resistant to linezolid. Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI. The comparison of adverse events is favorable to tedizolid under the circumstances of the clinical trials. This is a review of recent literature on tedizolid, its use in special populations and potential adverse effects. RECENT FINDINGS: Findings suggest that tedizolid can be used in SSTI in adolescents, those older than 65 years, obese individuals and patients with diabetic foot infections. Forthcoming research to determine the future uses of this drug in other clinical syndromes requires demonstration of tolerance whenever tedizolid is administered for longer than 6 days.We also speculate on missing data and potential future indications of tedizolid in the highly competitive field of the treatment of severe Gram-positive infections other than SSTI. SUMMARY: Tedizolid is a second-generation oxazolidinone, very convenient for treatment of SSTI, in search for other indications including nosocomial pneumonia and bone and joint infections. VIDEO ABSTRACT.

Systematic Therapeutic Drug Monitoring for Linezolid: Variability and Clinical Impact.

Linezolid serum trough (Cmin) and peak (Cmax) levels were determined prospectively in 90 patients. Adequate exposure was defined as a Cmin of 2 to 8 mg/liter. Therapy was empirical (73.3%) or targeted (26.7%). Wide interindividual variability in linezolid Cmin levels was recorded (0.1 to 25.2 µg/ml). Overall, 65.5% of the patients had out-of-range, 41.1% had subtherapeutic, and 24.4% had supratherapeutic trough levels. We did not find a correlation between abnormal levels and adverse events, in-hospital mortality, or overall poor outcome.

Legionnaires' disease.

Since first identified in early 1977, bacteria of the genus Legionella are recognised as a common cause of community-acquired pneumonia and a rare cause of hospital-acquired pneumonia. Legionella bacteria multisystem manifestations mainly affect susceptible patients as a result of age, underlying debilitating conditions, or immunosuppression. Water is the major natural reservoir for Legionella, and the pathogen is found in many different natural and artificial aquatic environments such as cooling towers or water systems in buildings, including hospitals. The term given to the severe pneumonia and systemic infection caused by Legionella bacteria is Legionnaires' disease. Over time, the prevalence of legionellosis or Legionnaires' disease has risen, which might indicate a greater awareness and reporting of the disease. Advances in microbiology have led to a better understanding of the ecological niches and pathogenesis of the condition. Legionnaires' disease is not always suspected because of its non-specific symptoms, and the diagnostic tests routinely available do not offer the desired sensitivity. However, effective antibiotics are available. Disease notification systems provide the basis for initiating investigations and limiting the scale and recurrence of outbreaks. This report reviews our current understanding of this disease.

Quality of the aetiological diagnosis of ventilator-associated pneumonia in Spain in the opinion of intensive care specialists and microbiologists.

INTRODUCTION: Current guidelines for the microbiological diagnosis of ventilator-associated pneumonia (VAP) are imprecise. Based on data provided by intensive care specialists (ICS) and microbiologists, this study defines the clinical practices and microbiological techniques currently used for an aetiological diagnosis of VAP and pinpoints deficiencies. METHODS: Eighty hospitals in the national health network with intensive care and microbiology departments were sent two questionnaires, one for each department, in order to collect data on VAP diagnosis for the previous year. RESULTS: Out of the 80 hospitals, 35 (43.8%) hospitals participated. These included 673 ICU beds, 32,020 ICU admissions, 173,820 ICU days stay, and generated 27,048 lower respiratory tract specimens in the year. A third of the hospitals (35%) had a microbiology department available 24/7. Most samples (83%) were tracheal aspirates. Gram stain results were immediately reported in around half (47%) of the hospitals. Quantification was made in 75% of hospitals. Molecular techniques and direct susceptibility testing were performed in 12% and one institution, respectively. Mean turnaround time for a microbiological report was 1.7 (SD; 0.7), and 2.2 (SD; 0.6) days for a negative and positive result, respectively. Telephone/in-person information was offered by 65% of the hospitals. Most (89%) ICS considered microbiological information as very useful. No written procedures were available in half the ICUs. CONCLUSIONS: Both ICS and microbiologists agreed that present guidelines for the diagnosis of VAP could be much improved, and that a new set of consensus guidelines is urgently required. A need for guidelines to be more effectively implemented was also identified in order to improve outcomes in patients with VAP.

[Future applications of mass spectrometry in microbiology]. / Perspectivas de futuro de la espectrometría de masas en microbiología.

MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometry (MS) has been vigorously introduced in many clinical microbiology laboratories for the rapid and accurate identification of bacteria and fungi. In fact, the implementation of this methodology can be considered a revolution in these laboratories. In addition to microbial identification, MALDI-TOF MS is being used for the detection of some mechanisms of antibiotic resistance and for the molecular typing of bacteria. A number of current and future applications that increase the versatility of this methodology may also be mentioned. Among these are its direct application on clinical samples, the detection of toxins or specific microbial antigens, and its application in the fields of virology and parasitology.

Use of rapid diagnostic techniques in ICU patients with infections.

BACKGROUND: Infection is a common complication seen in ICU patients. Given the correlation between infection and mortality in these patients, a rapid etiological diagnosis and the determination of antimicrobial resistance markers are of paramount importance, especially in view of today's globally spread of multi drug resistance microorganisms. This paper reviews some of the rapid diagnostic techniques available for ICU patients with infections. METHODS: A narrative review of recent peer-reviewed literature (published between 1995 and 2014) was performed using as the search terms: Intensive care medicine, Microbiological techniques, Clinical laboratory techniques, Diagnosis, and Rapid diagnosis, with no language restrictions. RESULTS: The most developed microbiology fields for a rapid diagnosis of infection in critically ill patients are those related to the diagnosis of bloodstream infection, pneumonia -both ventilator associated and non-ventilator associated-, urinary tract infection, skin and soft tissue infections, viral infections and tuberculosis. CONCLUSIONS: New developments in the field of microbiology have served to shorten turnaround times and optimize the treatment of many types of infection. Although there are still some unresolved limitations of the use of molecular techniques for a rapid diagnosis of infection in the ICU patient, this approach holds much promise for the future.

Bloodstream infections: trends and evolution of incidence and etiology in a 12-year period (2010-2021).

INTRODUCTION: The epidemiological evolution of bloodstream infections (BSIs) in the last decade is not clearly defined. Our aim was to analyze the changes in the workload in our institution and to describe the evolution of the incidence and etiology of BSIs in a 12-year period, including the COVID-19 pandemic. METHODS: All blood cultures received in the laboratory of a tertiary general hospital between 2010 and 2021 were analyzed. Bloodstream infection episodes refer to each episode of bacteremia or fungemia in each patient. Incidence rates per 1000 admissions and per 100,000 population were calculated. RESULTS: No significant changes in the incidence of BSI episodes/1000 admissions were observed (mean, 31.1), while estimated population-based incidences showed declining trends (mean, 182.8/100,000 inhabitants). There was a slight increase in BSI episodes per 1000 admissions caused by Gram-negatives (mean, 16.6/1000 admissions) and E. coli was the most frequent pathogen (mean, 8.5/1000 admissions). There was no significant rise in episodes caused by ESBL- and carbapenemase-producing E. coli or K. pneumoniae, with a decline in those caused by methicillin-resistant S. aureus. A spike in BSI episodes, fungal BSIs and catheter-related infections was detected in 2020, during the COVID-19 outbreak. CONCLUSIONS: No clear increase in the incidence of BSI episodes was detected in our center over this period. Gram-negatives are the most frequent etiology, with no clear rise in antimicrobial resistance phenotypes. The COVID-19 pandemic accounted for a small increase in BSI episodes in 2020, probably related to the increase of catheter-related infections.

Mixed bloodstream infections involving bacteria and Candida spp.

OBJECTIVES: Polymicrobial bloodstream infection (BSI) is an imprecisely defined entity purportedly associated with a worse outcome than monomicrobial BSI. This study examines trends in BSI episodes caused by bacteria and Candida spp. (mixed-BSI) in a large teaching hospital. METHODS: All episodes of BSI from January 2000 to December 2010 were reviewed. Three groups (n = 54 each) of patients were compared: all adults with mixed-BSI from January 2006 to December 2010 (cases) and randomly selected patients with polybacterial BSI (polyB-BSI) (Control 1) or Candida spp. BSI (Candida-BSI) (Control 2) in this same period. RESULTS: A total of 139 episodes of mixed-BSI were recorded (0.7% of all BSI, 6.9% of all poly-BSI and 18.0% of all Candida-BSI episodes). The incidence of mixed-BSI was 0.21 cases/1000 admissions, increasing from 0.08 (2000) to 0.34 (2010) cases/1000 admissions (P = 0.007). Mixed-BSI represented 11.8% and 22.9% of all episodes of candidaemia in 2000 and 2010, respectively (P = 0.011). Compared with polyB-BSI, mixed-BSI patients showed fewer malignancies, more frequent nosocomial or intravenous catheter BSI source and less frequent intra-abdominal origin, were more frequently admitted to an intensive care unit (ICU), received more antimicrobials and showed a longer hospital stay and higher mortality. Compared with Candida-BSI, mixed-BSI patients showed more severe underlying diseases, were more frequently admitted to an ICU or oncology-haematology unit, showed a higher APACHE II score, more often progressed to septic shock or multiorgan failure and received more antimicrobials. Mortality was similar. CONCLUSIONS: Mixed-BSI is a rare, distinct infection with a worse prognosis than polyB-BSI. We were unable to detect differences in the prognosis of mixed-BSI when compared with Candida-BSI.

In vitro study to assess modulation of Candida biofilm by Escherichia coli from vaginal strains.

Background: Vulvovaginal candidiasis (VVC) is caused by biofilm formation and epithelial invasion. In addition, Escherichia coli (EC) can establish a vaginal intracellular reservoir modulating Candida spp. biofilm production. We aimed to analyze the behavior of Candida albicans (CA) and EC biofilm both in single cultures and in co-cultures. Methods: We prospectively collected CA and EC isolates from vaginal swabs over 6 months. We selected positive cultures with both CA and EC (cases) and a comparator group with either CA or EC (controls). We analyzed overall biomass production and metabolic activity in single cultures and in co-cultures based on staining assays, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) to assess biofilm occupation. We also analyzed clinical manifestations. Results: We cultured 455 samples, 16 (3.5%) of which had CA and EC (cases); only CA or EC (controls) was detected, respectively, in 72 (15.8%) and 98 (21.5%). Biomass production and metabolic activity were significantly more pronounced in co-cultures in both groups. CLSM and SEM, on the other hand, showed the biofilm of each species to be significantly reduced when they were cultured together, with higher values in CA (percentage biofilm reduction: CA, 95.8% vs. EC, 36.2%, p < 0.001). There were no clinically significant differences between co-infected patients and patients infected only by C. albicans. Conclusion: Ours is the first study assessing co-cultures of CA and EC in a large collection of samples. We observed that coinfection of CA and EC was unusual (3.5%) and promoted high biomass, whereas microscopy enabled us to detect a reduction in biofilm production when microorganisms were co-cultured. No differences in symptoms were observed.

Rapid detection of Staphylococcus aureus in lower respiratory tract secretions from patients with suspected ventilator-associated pneumonia: evaluation of the Cepheid Xpert MRSA/SA SSTI assay.

A preclinical evaluation was conducted to evaluate the performance of the Cepheid Xpert assay on 135 lower respiratory tract secretions for detection of methicillin-resistant Staphylococcus aureus and S. aureus. Compared with the quantitative culture, the sensitivity, specificity, and positive and negative predictive values were 99.0%, 72.2%, 90.7%, and 96.3%, respectively.

[Diseases associated with bloodstream infections caused by the new species included in the old Streptococcus bovis group]. / Cuadros clínicos asociados a bacteriemia causada por las nuevas especies incluidas en el antiguo grupo Streptococcus bovis.

OBJECTIVE: We sought to identify possible diseases associated with bloodstream infections caused by new species of S. bovis group isolated in blood cultures and by studying patient records METHODS: Forty-four consecutive blood culture isolates initially designated S. bovis were further characterised using phenotypic methods Patient records were examined. RESULTS: We identified 15 Streptococcus gallolyticus subsp. gallolyticus, 24 Streptococcus gallolyticus subsp. pasteurianus, and 5 Streptococcus infantarius isolates in 44 BSI episodes. CONCLUSIONS: The association between S. bovis bacteraemia and endocarditis and/or colon carcinoma is highly dependent on the causative species. Streptococcus gallolyticus subsp. gallolyticus is a surrogate for endocarditis and/or bowel disease, whereas Streptococcus gallolyticus subsp. pasteurianus is a surrogate for hepato-biliary disease.

Faster infection diagnostics for intensive care unit (ICU) patients.

INTRODUCTION: The patient admitted to intensive care units (ICU) is critically ill, to some extent immunosuppressed, with a high risk of infection, sometimes by multidrug-resistant microorganisms. In this context, the intensivist expects from the microbiology service quick and understandable information so that appropriate antimicrobial treatment for that particular patient and infection can be initiated. AREAS COVERED: In this review of recent literature (2015-2021), we identified diagnostic methods for the most prevalent infections in these patients through a search of the databases PubMed, evidence-based medicine online, York University reviewers group, Cochrane, MBE-Trip, and Sumsearch using the terms: adult, clinical laboratory techniques, critical care, early diagnosis, microbiology, molecular diagnostic techniques, spectrometry and metagenomics. EXPERT OPINION: There has been an exponential surge in diagnostic systems used directly on blood and other samples to expedite microbial identification and antimicrobial susceptibility testing of pathogens. Few studies have thus far assessed their clinical impact; final outcomes will also depend on preanalytical and post-analytical factors. Besides, many of the resistance mechanisms cannot yet be detected with molecular techniques, which impairs the prediction of the actual resistance phenotype. Nonetheless, this is an exciting field with much yet to explore.