Early Empiric Therapy Research Articles

Updates on Antibiotic Regimens in Acute Cholecystitis.

Acute cholecystitis is one of the most common surgical diseases, which may progress from mild to severe cases. When combined with bacteremia, the mortality rate of acute cholecystitis reaches up to 10-20%. The standard of care in patients with acute cholecystitis is early laparoscopic cholecystectomy. Percutaneous cholecystostomy or endoscopic procedures are alternative treatments in selective cases. Nevertheless, antibiotic therapy plays a key role in preventing surgical complications and limiting the systemic inflammatory response, especially in patients with moderate to severe cholecystitis. Patients with acute cholecystitis have a bile bacterial colonization rate of 35-60%. The most frequently isolated microorganisms are Escherichia coli, Klebsiella spp., Streptococcus spp., Enterococcus spp., and Clostridium spp. Early empirical antimicrobial therapy along with source control of infection is the cornerstone for a successful treatment. In these cases, the choice of antibiotic must be made considering some factors (e.g., the severity of the clinical manifestations, the onset of the infection if acquired in hospital or in the community, the penetration of the drug into the bile, and any drug resistance). Furthermore, therapy must be modified based on bile cultures in cases of severe cholecystitis. Antibiotic stewardship is the key to the correct management of bile-related infections. It is necessary to be aware of the appropriate therapeutic scheme and its precise duration. The appropriate use of antibiotic agents is crucial and should be integrated into good clinical practice and standards of care.

Empirical antifungal therapy for health care-associated intra-abdominal infection: a retrospective, multicentre and comparative study

BackgroundCurrent guidelines recommend using antifungals for selected patients with health care-associated intra-abdominal infection (HC-IAI), but this recommendation is based on a weak evidence. This study aimed to assess the association between early empirical use of antifungals and outcomes in intensive care unit (ICU) adult patients requiring re-intervention after abdominal surgery.MethodsA retrospective, multicentre cohort study with overlap propensity score weighting was conducted in three ICUs located in three medical institutions in France. Patients treated with early empirical antifungals for HC-IAI after abdominal surgery were compared with controls who did not receive such antifungals. The primary endpoint was the death rate at 90 days, and the secondary endpoints were the death rate at 1 year and composite criteria evaluated at 30 days following the HC-IAI diagnosis, including the need for re-intervention, inappropriate antimicrobial therapy and death, whichever occurred first.ResultsAt 90 days, the death rate was significantly decreased in the patients treated with empirical antifungals compared with the control group (11.4% and 20.7%, respectively, p = 0.02). No differences were reported for the secondary outcomes.ConclusionThe use of early empirical antifungal therapy was associated with a decreased death rate at 90 days, with no effect on the death rate at 1 year, the death rate at 30 days, the rate of re-intervention, the need for drainage, and empirical antibiotic and antifungal therapy failure at 30 days.

Modern features of legionellosis

BACKGROUND: Community-acquired Legionella pneumonia, classified as atypical pneumonia, is an important problem worldwide. Late initiation of etiotropic therapy for Legionnaires’ disease worsens the prognosis and increases the risk of death.
 AIM: To clinically and epidemiologically characterize Legionnaires’ disease using data on its incidence in the Krasnodar region and to attract the attention of doctors to its timely diagnosis and the prescription of adequate etiotropic therapy.
 MATERIALS AND METHODS: A hospital cohort of 26 patients who were hospitalized between 2017 and 2022 was studied for legionellosis, which was confirmed in the laboratory by the detection of Legionella antigen in the urine using immunochromatography.
 RESULTS: The Krasnodar region is characterized by a sporadic incidence of legionellosis, which tends to increase in periods with high average humidity. Cases of legionellosis are recorded throughout the year, with peaks in summer and winter. The rise in incidence shifts annually and follows the month with the highest rainfall and average monthly temperature 20°C. Severe and moderate courses of legionellosis typically occur in men aged 50 years, with comorbid pathology and accompanied by lung damage of varying severity levels. Some patients may experience diarrhea (11.5%) and transient liver and kidney dysfunction. The nature of lung damage, such as polysegmental pneumonia, does not have clear clinical differential diagnostics, which makes early diagnosis difficult. An epidemiological anamnesis indicating contact with aerosol water, soil, and air conditioning systems has important diagnostic significance. Seeking specialized medical care after the 7th day of illness increases the risk of developing severe disease with complications.
 CONCLUSIONS: In severe community-acquired pneumonia, the epidemiological history must be considered, kidney and liver function should be assessed, a urine test must conducted for Legionella antigens, and early empirical therapy with fluoroquinolones and macrolides must be initiated.

Comparison of The Effect of Candida Score and Candida Colonization Index on Decrease in Candidemia Incidence in Our Intensive Care Unit

Aim: Since candidemia is an important cause of mortality and morbidity in hospitals, especially in intensive care units (ICU), those hospitalized in the ICU; In patients with risk factors such as invasive device use and undergoing abdominal surgery, early empirical antifungal therapy is recommended to reduce mortality according to the results of candida score (CS) and candida colonization index (CCI). In this study, the data of the patients who were followed up in the ICU, who were started on empirical treatment according to KS and CCI, were evaluated and their effects on the incidence of candidemia were analyzed. Method: Cultures taken from 100 patients hospitalized in the intensive care unit where adult patients were followed between 01.06.2018 and 01.08.2021 were examined. While investigating the colonization index of each patient, swab samples were taken once during the hospitalization from five main sites: mouth, nose, skin, perineum, and catheter. Samples taken with sterile swabs were inoculated on Sabouraud dextrose agar (SDA) plates and the plates were incubated at 35°C for 48 hours. The yeast colonies formed were defined according to their microscopic appearance and biochemical properties. CCI and CS of the patients were evaluated and fluconazole prophylaxis was started in patients with KS ≥3 or CCI ≥0.5. Results: A total of 500 culture samples from 100 non-neutropenic adult patients were analyzed (Mean of 5 cultures/patient). No growth was detected in any of the samples in 32 (32 %) of 100 patients, and growth was detected in at least one of the samples taken from 68 patients (68 %). Reproduction was detected from a total of 118 samples. Of the yeasts, 104 were identified as Candida albicans, 10 as Candida glabrata and 4 as Candida inconspicua. CS≥ 3 and CCI ≥0.5 in 11 (11%) patients, and CS≥3, CCI

Infections in Pregnancy

Abstract Infections in pregnant women tend to be more severe and pose unique treatment challenges. After all, the well-being of two individuals is at stake. Screening all pregnant women in early pregnancy for bacteriuria is recommended. Pyelonephritis and puerperal sepsis should be managed aggressively with appropriate empiric antibiotic choices. Increasing resistance in Enterobacterales is the complicating treatment of both these illnesses in the Indian setting. Influenza can lead to serious maternal and fetal outcomes; early empiric antiviral therapy and universal maternal vaccination are important. Dengue is an important cause of fever in pregnant women and can complicate vaginal and operative delivery due to thrombocytopenia. Falciparum malaria can now be treated with artemisinin-based combination therapy (ACT) in all trimesters. The drug of choice for scrub typhus is azithromycin; a combination of doxycycline and azithromycin can be considered in very severe disease. Treatment of both drug-sensitive and drug-resistant tuberculosis in pregnancy is similar to the nonpregnant. Safety data relating to bedaquiline and delamanid from animal models and cohort studies are reassuring.

Characteristics of antibiotic resistance of infectious pathogens in the wounded

ABSTRACT. This study examines the etiological structure and antibiotic resistance features of pathogens causing infectious complications in wounded patients receiving specialized medical care are considered. A total of 3845 clinical isolates were analyzed from wounded individuals admitted t o a multidisciplinary hospital for treatment. The analysis revealed that polyresistant pathogens, namely, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii were predominant among the isolated microorganisms. The prevalence of Acinetobacter baumannii varied based on the type of clinical material, with higher rates observed in wounds and respiratory, and urinary tract discharges. The polyresistant clinical isolates of Acinetobacter baumannii were sensitive to tigecycline and polymyxin, while Klebsiella pneumoniae and Pseudomonas aeruginosa were sensitive to polymyxin only. A comparison of the 2022 data with a previous study conducted in 2020 on wound discharges revealed a significant shift in the spectrum of pathogens causing wound infections. This shift involved an increase in the proportion of Acinetobacter spp., Bacillus spp., Enterococcus spp., Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as a decrease in the proportion of certain gram-negative bacteria, including Proteus spp. and Escherichia coli. Additionally, a notable five-fold reduction in the proportion of Streptococcus spp. and Staphylococcus aureus was observed. It is likely that early empirical therapy for combat wounds effectively prevents the development of wound infections associated with these pathogens. Bloodstream infections were primarily caused by coagulase-negative staphylococci (34.5%) and Klebsiella pneumoniae (27.8%). Notably, 80% of Staphylococcus spp. isolates were methicillin-resistant. The prolonged course of infectious complications associated with polyresistant strains and the challenges in selecting appropriate antibacterial therapy may contribute to the circulation of antibiotic-resistant nosocomial strains within the hospital environment. Therefore, it is crucial to increase the vigilance of the epidemiological service in addressing the high frequency of polyresistant pathogens to implement timely antiepidemic measures. Overall, these findings indicate the involvement of polyresistant gram-negative bacteria in the development of infectious complications during the inpatient treatment of wounded individuals.

Multi-drug resistant and rifampin-resistant tuberculosis in transplant recipients.

Management of multidrug-resistant (MDR) and rifampin-resistant (RR) tuberculosis is challenging. Data on transplant recipients is limited. We reviewed published literature to examine treatment choices, outcomes, and adverse effects from MDR-TB/RR-TB treatment in transplant recipients. Multiple databases from inception to 12/2022 were reviewed using the keywords "drug-resistant TB" or "drug-resistant tuberculosis" or "multidrug-resistant TB" or "multidrug-resistant tuberculosis". MDR-TB was defined as resistance to isoniazid (H) and rifampin (R), and RR if resistant to rifampin alone. Cases without patient-level data and reports which did not describe treatment and/or outcomes for MDR-TB were excluded. A total of 12 patients (10 solid organ transplants and two hematopoietic cell transplants) were included. Of these, 11 were MDR-TB and one was RR-TB. Seven recipients were male. The median age was 41.5 (range 16-60) years. Pre-transplant evaluation for the majority (8/12, 66.7%) did not reveal a prior history of TB or TB treatment, but 9/12 were from TB intermediate or high-burden countries. Seven patients were initially treated with the quadruple first-line anti-TB regimen. Those who had early RR confirmation (5/12) via Xpert MTB/RIF assay were initiated on alternative therapies. Final regimens were individualized based on susceptibility profiles and tolerability. Adverse events were reported in seven recipients, including acute kidney injury (n = 3), cytopenias (n = 3), and jaundice (n = 2). Four recipients died, with two deaths attributable to TB. The remaining eight patients who survived had functioning allografts at the last follow-up. MDR-TB treatment in transplant recipients is associated with many complications. Xpert MTB/RIF detected RR early and guided early empiric therapy.

Ten Years of KPC-Kp Bloodstream Infections Experience: Impact of Early Appropriate Empirical Therapy on Mortality.

In K. pneumoniae KPC (KPC-Kp) bloodstream infections (BSI), INCREMENT CPE score >7, Charlson Comorbidity Index (CCI) ≥3 and septic shock are recognized predictors of mortality, with a possible beneficial effect of combination therapy in seriously ill patients. We conducted a ten-year retrospective study including all KPC-Kp BSI in patients ≥18 years of age with the aim to evaluate the characteristics and impact of appropriate empirical therapy, either monotherapy or combination therapy, and targeted therapy on mortality. Appropriate therapy was defined as at least one active antimicrobial agent with in vitro activity against KPC-kp demonstrated by susceptibility testing, administered within 48 h from blood culture collection. The median age of the 435 analyzed patients was 66.09 years (IQR 54.87-73.98). The median CCI was 4. KPC-Kp colonization was present in 324 patients (74.48%). The probable origin of the KPC-Kp BSI was not identified in 136 patients (31.26%), whereas in 120 (27.59%) patients, it was CVC-related, and in 118 (27.13%), it was respiratory. Source control was achieved in 87 patients (72.5%) with CVC-related KPC-Kp BSI. The twenty-eight-day survival was 70.45% for empirical monotherapy, 63.88% for empirical combination therapy and 57.05% for targeted therapy (p = 0.0399). A probable source of KPC-Kp BSI other than urinary, CVC or abdominal [aHR 1.64 (IC 1.15-2.34) p = 0.006] and deferred targeted therapy [HR 1.67 (IC 1.12-2.51), p= 0.013] emerged as predictors of mortality, whereas source control [HR 0.62 (IC 0.44-0.86), p = 0.005] and ceftazidime/avibactam administration in empirical therapy [aHR 0.37 (IC 0.20-0.68) p = 0.002] appeared as protective factors. These data underline the importance of source control together with timing appropriateness in the early start of empirical therapy over the choice of monotherapy or combination therapy and the use of ceftazidime/avibactam against KPC-Kp BSI.

Impact of early empirical antifungal therapy on prognosis of sepsis patients with positive yeast culture: A retrospective study from the MIMIC-IV database.

Mortality and other clinical outcomes of culture-negative and culture-positive among patients with fungal sepsis have not been documented, and whether antifungal therapy prior to fungal culture reports is related to decreased mortality among patients remains largely controversial. This study aimed to determine the mortality and other clinical outcomes of patients with positive yeast cultures and further investigate the effects of initial empiric antifungal therapy. A retrospective study was conducted among septic patients using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients with sepsis were divided into two groups based on first fungal culture status during intensive care unit (ICU) stay, and initial empirical antifungal therapy was prescribed based on physician's experience prior to fungal culture reports within 48 h. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30-day all-cause mortality, 60-day all-cause mortality, length of ICU stay and length of hospital stay. Multivariate logistic regression, propensity score matching (PSM), subgroup analyses and survival curve analyses were performed. This study included 18,496 sepsis patients, of whom 3,477 (18.8%) had positive yeast cultures. Patients with positive yeast cultures had higher in-hospital all-cause mortality, 60-day all-cause mortality, and longer lengths of ICU stay and hospital stay than those with negative yeast cultures after PSM (all p < 0.01). Multivariate logistic regression analysis revealed that positive yeast culture was a risk factor for in-hospital mortality in the extended model. Subgroup analyses showed that the results were robust among the respiratory infection, urinary tract infection, gram-positive bacterial infection and bacteria-free culture subgroups. Interestingly, empiric antifungal therapy was not associated with lower in-hospital mortality among patients with positive yeast cultures, mainly manifested in stratification analysis, which showed that antifungal treatment did not improve outcomes in the bloodstream infection (odds ratio, OR 2.12, 95% CI: 1.16-3.91, p = 0.015) or urinary tract infection groups (OR 3.24, 95% CI: 1.48-7.11, p = 0.003). Culture positivity for yeast among sepsis patients was associated with worse clinical outcomes, and empiric antifungal therapy did not lower in-hospital all-cause mortality in the bloodstream infection or urinary tract infection groups in the ICU.

Survival Outcome of Empirical Antifungal Therapy and the Value of Early Initiation: A Review of the Last Decade.

This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in addition to a hand search and experts' suggestions. Fourteen cohort studies and two randomized clinical trials reporting the survival outcome of empirical antifungal therapy were included in this review. Two studies reported the association between early empirical antifungal therapy (EAFT) and survival rates in a hematological cancer setting, and fourteen studies reported the outcome in patients in intensive care units (ICU). Six studies reported that appropriate EAFT decreases hospital mortality significantly; ten studies could not demonstrate a statistically significant association with mortality rates. The inconsistency of the results in the literature can be attributed to the studies' small sample size and their heterogeneity. Many patients who may potentially benefit from such strategies were excluded from these studies. While EAFT is practiced in many settings, current evidence is conflicting, and high-quality studies are needed to demonstrate the true value of this approach. Meanwhile, insights from experts in the field can help guide clinicians to initiate EAFT when indicated.

P090 Biofilm forming capabilities in multi-drug resistant Candida species with special emphasis on Candida auris isolated from intensive care unit patients

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectiveBiofilm forming capabilities of isolates obtained from intensive care unit (ICU) patientsTo study the trend of antifungal susceptibility of Candida isolates using MIC method by VITEK-2MethodsThis is a hospital-based prospective study in which Candida isolates from urine, blood, and BAL fluid of ICU patients from March 2021 to February 2022 were included. Conventional identification methods were performed for all isolates, speciation was done by MALDI-TOF. Biofilm formation by microtiter plate method and anti-fungal susceptibility was performed by VITEK-2.ResultsIn the present study, out of 360 positive fungal isolates, 20% Candida isolates (72) were obtained from the ICU patients. Candida tropicalis (45.2%) was the most common fungal isolate among all non-albicans Candida spp followed by C. parapsilosis, and C. auris. The biofilm formation was tested by microtiter plate method on Candida isolates. Candida auris showed strong biofilm formation tendency (28.5%). In this study, 16.6% of Candida isolates had resistance against fluconazole out of which 6 isolates were multiresistant to other antifungal. Use of automated machines helped in early identification of these species 24-48 h less than the conventional methods.ConclusionParallel increase in number of non-albicans Candida beside C. albicans could be because of patients on prolonged antimicrobial therapy, immunosuppressive drugs, varied comorbidities and species selection in the presence of certain antifungals, given the higher level of resistance expressed by NAC. Biofilm production a probable cause for increasing antifungal resistance and therapeutic failure. NAC species are emerging as potential threats to cause infection and posing a therapeutic challenge. Early empirical antifungal therapy and further research to improve diagnostic, prevention, and therapeutic strategies are necessary to reduce the considerable morbidity and mortality.

Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management.

Hyperammonemia occurs frequently in the critically ill but is largely confined to patients with hepatic dysfunction or failure. Non-hepatic hyperammonemia (NHHA) is far less common but can be a harbinger of life-threatening diagnoses that warrant timely identification and, sometimes, empiric therapy to prevent seizures, status epilepticus, cerebral edema, coma and death; in children, permanent cognitive impairment can result. Subsets of patients are at particular risk for developing NHHA, including the organ transplant recipient. Unique etiologies include rare infections, such as with Ureaplasma species, and unmasked inborn errors of metabolism, like urea cycle disorders, must be considered in the critically ill. Early recognition and empiric therapy, including directed therapies towards these rare etiologies, is crucial to prevent catastrophic demise. We review the etiologies of NHHA and highlight the first presentation of it associated with a concurrent Ureaplasma urealyticum and Mycoplasma hominis infection in a previously healthy individual with polytrauma. Based on this clinical review, a diagnostic and treatment algorithm to identify and manage NHHA is proposed.

Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial

IntroductionSub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of...

Confirmed severe acute respiratory syndrome coronavirus 2 encephalitis in cerebrospinal fluid: a case report

BackgroundPatients with severe acute respiratory syndrome coronavirus 2 infection show various clinical manifestations, including neurological . Altered consciousness due to severe acute respiratory syndrome coronavirus 2 encephalitis is a very threatening condition if not treated immediately.Case presentationWe present the case of a 34-year-old Asian female who tested positive for severe acute respiratory syndrome coronavirus 2 infection using a nasopharyngeal swab sample and presented with acute changes in consciousness without typical respiratory symptoms. Empiric therapy was immediately and simultaneously given with cerebrospinal fluid analysis using polymerase chain reaction, which later also showed positive results for severe acute respiratory syndrome coronavirus 2 infection.ConclusionsIt is important to consider the diagnosis of severe acute respiratory syndrome coronavirus 2 encephalitis when a patient presents with acute altered consciousness and no typical respiratory symptoms. Early empiric therapy can improve patient outcomes.

Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study.

BackgroundThe frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection.MethodsWe included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality.ResultsAmong 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33–1.95) and fungal (OR, 2.20; 95% CI, 1.28–3.76) coinfections.ConclusionsViral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

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-β-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.

Противовирусная и антибактериальная терапия в лечении внебольничных пневмоний

Работа посвящена систематизации подходов к противовирусной и антибактериальной терапии в лечении внебольничных пневмоний. В настоящее время пневмония является основной причиной летальности среди всех инфекционных осложнений во всех возрастных группах и шестой ведущей причиной смерти у подобной категории больных старше 65 лет. Основным компонентом в комплексном лечении больных с гриппозной пневмонией, осложненной бактериальной инфекцией, является своевременное назначение адекватной антивирусной и антибактериальной терапии.Проведение антивирусной терапии следует начинать на раннем этапе заболевания, основываясь на клинической картине болезни, не дожидаясь лабораторного подтверждения гриппа, т.к. разброс чувствительности к экспресс-тестам может составлять от 10 до 70 %.Противовирусная терапия основана на использовании ингибиторов нейраминидазы, которые являются одними из основных препаратов для лечения вирусных пневмоний и гриппоподобных заболеваний как у взрослых, так и у детей. А проведение ранней эмпирической антимикробной терапии целесообразно у больных с признаками вирусного поражения легких при наличии у них сопутствующих гнойно-воспалительных процессов.

A randomized, double-blind, placebo-controlled clinical trial of fluconazole as early empiric treatment of coccidioidomycosis pneumonia (Valley Fever) in adults presenting with community-acquired pneumonia in endemic areas (FLEET-Valley Fever)

IntroductionCoccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown. MethodsPhase IV randomized, double-blind, placebo-controlled trial in individuals aged 18 years or older with CAP who met all eligibility criteria in Coccidioides endemic regions in the US. Eligible participants with CAP were randomized to receive either fluconazole (400 mg daily) or matching placebo for 42 days and were subsequently monitored for clinical resolution of their illness. ObjectivesThe primary objective was to assess the clinical response of early empiric antifungal therapy with fluconazole through Day 22 in subjects with PPC who were adherent to the study intervention. Secondary objectives included: assessments of the impact of early empiric antifungal therapy with fluconazole through Day 22 and 43 in subjects with PPC regardless of adherence, comparisons of the clinical response and its individual components over time by treatment group in subjects with PPC, assessments of days lost from work or school, hospitalization, and all-cause mortality. DiscussionThis trial was halted early due to slow enrollment (72 participants in one year, 33 received fluconazole and 39 received placebo). Of those enrolled, eight (11%) met the study definition of PPC. The study design and challenges are discussed.

Severe alcoholic hepatitis-associated infection

Patients with severe alcoholic hepatitis is sensitive to concurrent infection and impact glucocorticoid response and disease prognosis. Glucocorticoids can increase the incidence and of serious infections and fungal infections. Among them, Gram-negative bacterial infections are the major one, and invasive fungal infections are not uncommon. Early diagnosis and empiric anti-infective therapy are important means for severe alcoholic hepatitis with concurrent infection. Anti-infective strategies covering multiple drug-resistant bacteria should be timely formulated after determining the high risk of multiple drug-resistant bacterial infections.

Optimizing Antimicrobial Drug Dosing in Critically Ill Patients.

A fundamental step in the successful management of sepsis and septic shock is early empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens; (2) they should be administered in the appropriate dose, (3) by the correct route, and (4) using the correct mode of administration to achieve successful concentration at the infection site. In critically ill patients, antimicrobial dosing is a common challenge and a frequent source of errors, since these patients present deranged pharmacokinetics, namely increased volume of distribution and altered drug clearance, which either increased or decreased. Moreover, the clinical condition of these patients changes markedly over time, either improving or deteriorating. The consequent impact on drug pharmacokinetics further complicates the selection of correct drug schedules and dosing during the course of therapy. In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. We aim to review the available literature to assess the challenges, impact, and tools to optimize individualization of antimicrobial dosing to maximize exposure and effectiveness in critically ill patients.