Antimicrobial Drug Therapy Research Articles

Therapeutic Drug Monitoring and Biomarkers; towards Better Dosing of Antimicrobial Therapy.

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used to adjust and individualise drug regimens until predefined pharmacokinetic exposure targets are achieved. Minimum inhibitory concentration (drug susceptibility) is the best available pharmacodynamic parameter but is associated with many limitations. Identification of other pharmacodynamic parameters is necessary. Repurposing diagnostic biomarkers as pharmacodynamic parameters to evaluate treatment response is attractive. When combined with therapeutic drug monitoring, it could facilitate making more informed dosing decisions. We believe the approach has potential and justifies further research.

Benefit of intrapleural fibrinolytic therapy in the treatment of complicated parapneumonic effusion and empyema.

Our study aimed to assess the benefit of intrapleural fibrinolysis before resorting to surgery to treat complicated parapneumonic effusion and empyema. We conducted a retrospective and descriptive study, including all patients hospitalized in the intensive care unit (ICU) of the Abderhaman Mami hospital, Tunisia for empyema treated with instillation of intrapleural fibrinolytic therapy between the 1st January 2000 and 31st December 2016. In all patients, empyema was diagnosed on clinical features, imaging findings (chest X-ray, thoracic echography and/or computed tomography (CT), and microbiological data. The fibrinolytic agent used was streptokinase. The efficiency of intrapleural fibrinolytic therapy was judged on clinical and paraclinical results. Among 103 cases of complicated parapneumonic effusion and empyema, 34 patients were included. The mean age was 34 years [15-81] with a male predominance (sex ratio at 2.77). Median APACH II score was 9. Fifty (50%) of the patients (n=17) had no past medical history; addictive behavior was described in 17 patients (50%). All patients were admitted for acute respiratory failure and one patient for septic shock. Pleural effusion was bilateral in 7 patients. Bacteria isolated were Streptococcus pneumonia (6 cases), Staphylococcus aureus (3 cases, including one which methicillin-resistant), Staphylococcus epidermidis (1 case), anaerobes (5 cases), and Klebsiella pneumoniae (1 case). First-line antimicrobial drug therapy was amoxicillin-clavulanate in 20 patients. A chest drain was placed in all cases in the first 38 hours of ICU admission. The median number of fibrinolysis sessions was 4 [2-9] and the median term of drainage was 7 days [3-16]. No side effects were observed. Video-assisted thoracoscopic surgery was proposed in 5 patients. The median length of hospitalization stay was 15 days [6-31]. One patient died due to multi-organ failure.

Healthcare-Associated Infections Caused by Mycolicibacterium neoaurum.

Mycolicibacterium neoaurum is a rapidly growing mycobacterium and an emerging cause of human infections. M. neoaurum infections are uncommon but likely underreported, and our understanding of the disease spectrum and optimum management is incomplete. We summarize demographic and clinical characteristics of a case of catheter-related M. neoaurum bacteremia in a child with leukemia and those of 36 previously reported episodes of M. neoaurum infection. Most infections occurred in young to middle-aged adults with serious underlying medical conditions and commonly involved medical devices. Overall, infections were not associated with severe illness or death. In contrast to other mycobacteria species, M. neoaurum was generally susceptible to multiple antimicrobial drugs and responded promptly to treatment, and infections were associated with good outcomes after relatively short therapy duration and device removal. Delays in identification and susceptibility testing were common. We recommend using combination antimicrobial drug therapy and removal of infected devices to eradicate infection.

Antimicrobial potentials of plant extracts against drug resistant bacteria

Antimicrobial resistance (AMR) is a serious and growing threat to human health. The development of new antibiotics is limited and slow. The tradition of synergy in herbal medicine is being used as a source of research ideas. The in vitro findings were that most of the research reported synergy both within plants and between plants and antibiotics. Whole plant extracts and combinations of compounds were shown to be more effective antimicrobials than isolated constituents. New sources of antimicrobial drugs need to be identified and improved strategy should be developed to combat multidrug resistance problem in pathogenic bacteria. Plant extract and phytochemicals demonstrating antimicrobial action needs to be exploited for their synergistic action between extracts and with antibiotics to exploit it in modern phytomedicine and combinational therapy. In the present study alcoholic extracts of medicinal plants were screened for their antimicrobial efficacy against drug resistant bacteria. The extracts of Hemidesmus indicus,and Carum copticum, showed promising action against one or more drug resistant bacteria with MIC ranged from 0.53 mg/ml to 7.80 mg/ml which has indicated their potential to be exploited in antimicrobial therapy and combination drug therapy after careful evaluation in vivo model.

#6437 INTRABDOMINAL ABSCESS: AN UNEXPECTED CAUSE OF POSTPARTUM SEPSIS IN A VAGINALLY DELIVERED WOMAN WITH PREGNANCY RELATED ACUTE KIDNEY INJURY

Abstract Pregnancy related-Acute kidney injury (PR-AKI) is a life-threatening complication with substantial fetal and maternal mortality and morbidity. AKI is associated with increased risk of infection and/or sepsis. Intra-abdominal infections account for 11.9% of infections that complicate AKI among critically ill patients. The pathophysiology is not fully understood, several theories have been proposed; of which, AKI associated hypervolemia leads to tissue edema and bacterial translocation. Moreover, AKI induces a hyper-inflammatory state and suppresses the immune system, this may present a greater predisposition for infection. Here we report a rare case of intra-abdominal abscess presented in a woman with recovering PR-AKI three months following normal vaginal delivery. Case presentation A 20-year-old, previously healthy female patient, was admitted due to severe postpartum hemorrhage (PPH) complicating a full-term vaginal delivery. On admission, blood pressure was 170/70, heart rate was 100 beats/min, and respiratory rate was 22 breaths/min. The patient developed oliguria, generalized edema, and fever (38.50c). The blood tests are revealed in Table I. The patient had elevated liver enzymes (SGOT 197 IU/L, and SGPT 117 IU/L). The patient was started on supportive treatment with packed RBC, platelet transfusion, and fresh frozen plasma. Empiric antibiotic was administrated. The patient subsequently had general improvement and was discharged 17 days after delivery with partial recovery of kidney function. Three months later, the patient presented with throbbing pain in the lower abdomen and fever. Abdominal examination revealed pelvi-abdominal fullness along with mild tenderness with no guarding or rigidity. No obvious palpable lumps were detected. No abnormities were detected in per vaginal and per rectal examinations. CT scan was performed and revealed a large sized collection in the lower abdomen sized 6.5x5x9 cm. Ultrasound guided aspiration of 60 ml pus confirmed the diagnosis of intraabdominal abscess. Intravenous antibiotics were started with percutaneous drainage of the abscess. Discussion Intraabdominal abscess is a serious ailment, and it is associated with high mortality and morbidity if left untreated. An intra-abdominal abscess can cause symptoms such as prolonged ileus, anorexia, fever, and abdominal pain. Septic shock may eventually develop in case of delayed treatment. However rare, there should be a causative factor. Intraabdominal abscess following a normal vaginal delivery is very rare and not reported with PR-AKI. CT scan is still the most useful technique for diagnosis and treatment. Additionally, it can help guide percutaneous drainage by locating the abscess in relation to the viscera of the abdomen. The use of adequate antimicrobial drug therapy in combination is a fundamental approach. It is therefore of great importance to consider symptoms such as atypical abdominal distension or pain in women in the postpartum period and to provide thorough comprehensive evaluation. Early diagnostic consideration greatly lessens patients’ morbidity and mortality.

Pattern of adverse drug reactions reported at the adverse drug reaction monitoring centre at tertiary care teaching hospital in North India

Background: The aim of the present study was to determine the pattern of adverse drug reactions (ADRs) reported at ADR monitoring centre (AMC) in Punjab. Methods: This observational retrospective study was done in department of Pharmacology, GGS Medical College and Hospital, Faridkot from September 2020 to August 2021. A total of 148 ADRs were reported during the study period. Each ADR was analyzed for demographic data and characteristics of ADR. Assessment of causality, severity and preventability was done according to WHO UMC scale, modified Hartwig and Siegel scale and Modified Schumock and Thornton Preventability Scale respectively. Results: A total of 148 ADRs were reported from both outpatients and in patients of various departments. Most of the ADRs were found in males (55%) and patients of age group 31-45 years (33%). Majority of ADRs were reported from dermatology department (40%). Overall, 38% of ADRs were due to antimicrobial drugs. Most of the ADRs were reported as possible (57%), followed by probable (41%) as per WHO causality assessment. Most of the ADRs were moderate severity (83%). 97% of the ADRs were found to be definitely preventable type. Conclusions: We concluded that most of the ADRs were reported from antimicrobial drugs, so it is advisable to have close monitoring of the antimicrobial drug therapy to prevent ADRs in the patients. Although the majority of ADRs were moderate in nature but mostly were recovered. The study of ADRs in a particular institute using demographic patterns will contribute to patient safety by sensitizing the clinicians in that particular institute.

Effect of dry cow therapy on antimicrobial resistance of mastitis pathogens post-calving.

The aim of this study was to evaluate the effect of dry cow therapy (DCT) on the antimicrobial resistance (AMR) profile of mastitis pathogens post-calving. A repository of isolates based on a DCT trial was utilized for the current study. A stratified random survey sample of cows from the trial were identified within the strata of season, herd, and trial treatment resulting in 382 cows. All isolates from the 382 cows were selected for the current study, which identified 566 isolates from milk samples collected at dry off (S1), post-calving (S2), and at the first clinical mastitis event up to 150 days in milk (S3). The AMR profiles were determined using broth microdilution method. Less than 10% of the coagulase-negative Staphylococcus species (CNS) isolates (n = 421) were resistant to tetracycline, ceftiofur, penicillin/novobiocin or erythromycin, while higher proportions of resistance to sulfadimethoxine (72%) and penicillin (28%) were observed. All Staphylococcus aureus (S. aureus) isolates (n = 4) were susceptible to all tested AMD except sulfadimethoxine, to which all isolates were resistant. Similarly, all Streptococcus spp. (n = 37) were susceptible to penicillin, penicillin/novobiocin, and ampicillin while resistant to tetracycline (17%). All coliforms (n = 21) were susceptible to ceftiofur, but resistance was recorded for sulfadimethoxine (70%), cephalothin (56%), and tetracycline (43%). The increased resistance percent from S1 to S2 was observed in CNS isolates from AMD-treated cows, with the highest increase recorded for penicillin (12.2%). Parametric survival interval regression models were used to explore the association between antimicrobial drug (AMD) therapy at dry off and the AMR phenotype post-calving. The accelerated failure-time metric was adopted to minimum inhibitory concentration measurements to permit interpretation of model exponentiated coefficients. Models for cows with CNS isolated at both S1 and S2 showed increased resistance against cephalothin, oxacillin, and ceftiofur in cows that received DCT from the same drug class, or a class with a shared resistance mechanism. In contrast, resistance of CNS isolates to tetracycline were associated with any AMD therapy at dry off. Resistance of CNS isolates to Penicillin decreased in CNS isolates in cows that received any AMD therapy at dry off compared to those that didn't. The study provided evidence that dry-cow IMM AMD was associated with AMR post-calving.

Antimicrobial use-related drug therapy problems and associated factors among patients in the medical ward of Wachemo University Nigist Eleni Mohammed Memorial Comprehensive Specialized Hospital, Southwest Ethiopia.

This study assessed the antimicrobial use-related drug therapy problems (DTPs) among patients admitted to the medical ward of Wachemo University Nigist Eleni Mohammed Memorial Comprehensive Specialized Hospital (WCUNEMMCSH), Southwest Ethiopia. A hospital-based prospective observational study design was used to assess antimicrobial use-related DTPs among patients admitted to the medical ward of WCUNEMMCSH from June to August 2021. Data were collected using a structured data abstraction format. In all, 128 patients admitted to the medical ward were enrolled. Among the study participants, at least one form of antimicrobial DTP occurred in 98 (76.6%) of them. The most prevalent DTPs were unnecessary drug treatment in 42 (32.8%), the need for additional drug treatment in 36 (28.1%), and non-adherence in 30 (23.4%) of the patients. There were a total of 288 antimicrobial drug orders. Ceftriaxone 120 (41.7%) and azithromycin 69 (24.0%) were the most commonly prescribed antimicrobial drugs. In multivariate logistic analysis, the length of hospital stay (adjusted odds ratio (AOR) = 2.97, 95% confidence interval (CI): 1.06-8.32; p = 0.04) and the number of diagnosed diseases (AOR = 3.10, 95% CI: 1.12-8.15, p = 0.02) were predictors of antimicrobial use-related DTPs. Antimicrobial use-related DTPs are common among patients admitted to the medical ward of WCUNEMMCSH. Health professionals should work together to reduce the high prevalence of DTPs among medical ward admitted patients in this hospital.

Antimicrobial Drug Therapy Problems Among Patients in the Outpatient Department of Ataye Hospital, Northeast Ethiopia.

BackgroundAntimicrobial drug therapy problems refer to incorrect and inappropriate utilization of antimicrobials which affect patient’s health outcomes and results in bacterial resistance. Incorrect use of antimicrobial agents is a key driver for the spread of antimicrobial drug resistance. Improving drug therapy problems has an important effect on the patients’ health, treatment costs, and enhancing patients’ quality of life. Hence, the aim of the present study was to assess antimicrobial drug therapy problems among patients in the Outpatient Department of Ataye hospital, Northeast Ethiopia.MethodsA hospital-based retrospective cross-sectional study design was used to assess antimicrobial drug therapy problems among patients in Ataye hospital from September 2018 to February 2019. Data were collected by trained graduating pharmacy students by reviewing medical records of patients using checklists and questionnaires.ResultsA total of 248 patient cards were included in this study. At least one antimicrobial drug therapy problem had occurred among 96 (38.7%) of the study participants. The most common drug therapy problem was the need for additional drug therapy which was incurred by 38 (15.3%) of the study participants and ineffective antimicrobial therapy was experienced by 22 (8.9%) of the patients. Tetracyclines 25 (26%), fluoroquinolones 19 (19.8%), and penicillins 18 (18.8%) were the most common classes of antimicrobials prone to drug therapy problems.ConclusionThe current study revealed that nearly two-fifths of the study participants had experienced at least one form of antimicrobial drug therapy problem. The most common drug therapy problem was the need for additional drug therapy and the use of ineffective antimicrobial therapy. Tetracyclines, fluoroquinolones, and penicillins were the main classes of antimicrobials involved in the drug therapy problem.

Bacterial Pattern and Susceptibility of Antimicrobial Agents in Cancer Patient with Infection

Introduction: Cancer patients are most vulnerable to develop infection during anticancer therapy which could be life threatening. Therefore, prompt administration of appropriate antimicrobial drug therapy is often essential to prevent mortality and morbidity in such patients. Spectrum of the infection causing organisms is continuously changing throughout the world along with their susceptibility to antimicrobials drugs. Aims: The aims of the study were to identify the bacterial pattern and their susceptibility to antimicrobials in cancer patients with infection and to help develop a guideline for the rational and appropriate use of antimicrobial in these patients. Materials and methods: It was an observational study conducted from January 2013 to December 2014 at the National Institute of Cancer Research and Hospital (NICRH), Mohakhali, Dhaka. We evaluated 517 blood and other specimens from cancer patients of both sexes and all ages under anticancer therapy suspected of having infection. Result: Blood culture was done in 53 patients of them 8 (15.09%) were proved to be culture positive. In case of urine and wound culture the rates of positivity were 37.79% & 73.98% respectively. In suspected cases culture for anaerobic organism was done but no such organism was found. Major isolated organisms in different cultures were E. coli, Staphylococcus aureus, Pseudomonas and Proteus. Imipenem, gentamicin, cotrimoxazole were the most sensitive antibiotics. However, in most cases amoxicillin, cephalexin and nalidixic acid were mostly resistant. Conclusion: Empirical use of amoxicillin or cephalexin is usually not useful and routine use of anaerobic culture is not necessary.

Acute Hematogenous Bacterial Osteoarticular Infections in Children.

1. Nathan Donaldson, DO* 2. Julia Sanders, MD* 3. Jason Child, PharmD† 4. Sarah Parker, MD‡ 1. *Division of Orthopedic Surgery and 2. ‡Division of Infectious Diseases, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO 3. †Department of Pharmacy, Children’s Hospital Colorado, Aurora, CO * Abbreviations: ADE: : adverse drug event CRMO: : chronic recurrent multifocal osteomyelitis CRP: : C-reactive protein CT: : computed tomography ESR: : erythrocyte sedimentation rate MRI: : magnetic resonance imaging MRSA: : methicillin-resistant Staphylococcus aureus MSSA: : methicillin-susceptible Staphylococcus aureus OAI: : osteoarticular infection WBC: : white blood cell Management of pediatric acute hematogenous osteoarticular infections has changed in various ways during the past decade, including the description of new pathogens and updated diagnostic and treatment strategies (such as infected source sampling and an early switch to oral therapy). After completing this article, readers should be able to: 1. Understand what predisposes children of different age groups to acute hematogenous osteoarticular infections (OAIs), particularly the role of anatomy and differing pathogenic susceptibilities. 2. Recognize the symptoms present in children with OAIs and their most common differential diagnoses. 3. Understand the most effective imaging techniques and laboratory tests/cultures to diagnose an OAI and how to interpret them. 4. Understand the benefits and limitations of therapeutic surgery and source sampling (biopsy/aspirate) and when to commence antimicrobial drug therapy. 5. Recognize the most common causative pathogens and the most effective antimicrobial drugs for their treatment. 6. Determine how long a patient should be taking intravenous and oral therapy and under what conditions they should switch from intravenous to oral antimicrobial agents. 7. Understand the recommended follow-up after diagnosis, including when to expect normalization of laboratory values in patients with uncomplicated OAIs. 8. Recognize complicated OAIs and their possible long-term sequelae. Pediatric osteoarticular infections (OAIs) include infections of the bones (osteomyelitis) and joints (septic arthritis). Pathogenic organisms may be introduced into these normally sterile sites via direct inoculation (eg, trauma or surgery) or via erosion from a contiguously infected source (eg, chronic ulcer), but organisms are mostly hematogenously delivered. Bacteria are the most common pathogens to cause OAIs, but mycobacteria, fungi, and viruses can also infect these tissues. If diagnosed in the first 10 to 14 days, these infections are …

Community Origin and Previous Use of Antimicrobials Increase the Risk of Nosocomial Multidrug-resistant Bacteria Colonisation in the Intensive Care Unit in a Brazilian Hospital

Background: Hospitalised patients are often surrounded by microorganisms, and antibiotic-resistant pathogens are a major and growing threat to public health. Objective: This study aimed to investigate the epidemiology and the risk factors for colonisation by multidrug-resistant organisms (MDROs) in a Brazilian hospital. Methods: Patients in the Intensive Care Unit (ICU) who underwent nasal and rectal swab cultures for the surveillance of colonisation by MDROs were evaluated in a retrospective study. MDROs were determined by routine microbiological cultures. Results: Of the 785 patients included in this study, 86 presented positive results for MDRO colonisation. Overall, the most frequently isolated organism was Klebsiella pneumoniae (41.9%), followed by Escherichia coli (33.7%). The main type of resistance was the production of extended-spectrum beta-lactamases (ESBL). The prevalence of MDRO infections was significantly associated with the patient's origin (community or hospital-acquired). Having been submitted to previous antimicrobial drug therapy was significantly associated with MDRO infection (relative risk [RR]: 4.02 [2.60 - 6.23]). Conclusion: MDRO ICU colonisation was variable, with similar frequencies as other centres, and important factors, including previous hospital stay and antibiotic use, were closely related to MDRO colonisation. Therefore, control interventions should reduce their rates, especially considering the particularities of each geographic centre.

Combined systemic (fluconazole) and topical (metronidazole + clotrimazole) therapy for a new approach to the treatment and prophylaxis of recurrent candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) is an important pathological and infectious condition that can greatly impact a woman's health and quality of life. Clinical and epidemiological studies show that different types of therapies are able to eliminate the signs and symptoms of mycotic vaginitis in the acute phase, but so far none of these has proved able to significantly reduce the risk of long-term recurrence. In this review, based on the available literature and original data from a preliminary in-vitro microbiological study on the compatibility between fluconazole, clotrimazole and metronidazole a new therapeutic approach to RVVC is discussed and presented. The treatment proposed is a combined scheme using both systemic antimicrobial drug therapy with oral fluconazole 200 mg and topical drug therapy using the association metronidazole 500 mg and clotrimazole 100 mg (vaginal ovules) with adjuvant oral probiotic therapy. In detail, at the time of diagnosis in the acute symptom phase, we propose the following treatment scheme: fluconazole 200 mg on day 1, 4, 11, 26, then 1 dose/month for 3 months at the end of the menstrual cycle; plus metronidazole/clotrimazole ovules 1/day for 6 days the first week, then 1 ovule/day for 3 days the week before the menstrual cycle for 3 months; plus probiotic 1 dose/day for 10 days for 3 months starting from the second month to the end of the menstrual cycle. This scheme aims to address the recurrent infection aggressively from the outset by attempting not only to treat acute symptoms, but also to prevent a new event by countering many of the potential risk factors of recurrence, such as the intestinal Candida reservoir, the mycotic biorhythm, the formation of biofilm, the phenotype switching and the presence of infections complicated by the presence of C. non albicans or G. Vaginalis, without interfering, but rather favoring the restoration of the vaginal lactobacillus species. Future clinical studies will be useful to confirm the proposed scheme.

Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance

BackgroundContinuing evolution of the Mycobacterium tuberculosis (Mtb) complex genomes associated with resistance to anti-tuberculosis drugs is threatening tuberculosis disease control efforts. Both multi- and extensively drug resistant Mtb (MDR and XDR, respectively) are increasing in prevalence, but the full set of Mtb genes involved are not known. There is a need for increased sensitivity of genome-wide approaches in order to elucidate the genetic basis of anti-microbial drug resistance and gain a more detailed understanding of Mtb genome evolution in a context of widespread antimicrobial therapy. Population structure within the Mtb complex, due to clonal expansion, lack of lateral gene transfer and low levels of recombination between lineages, may be reducing statistical power to detect drug resistance associated variants.ResultsTo investigate the effect of lineage-specific effects on the identification of drug resistance associations, we applied genome-wide association study (GWAS) and convergence-based (PhyC) methods to multiple drug resistance phenotypes of a global dataset of Mtb lineages 2 and 4, using both lineage-wise and combined approaches. We identify both well-established drug resistance variants and novel associations; uniquely identifying associations for both lineage-specific and -combined GWAS analyses. We report 17 potential novel associations between antimicrobial resistance phenotypes and Mtb genomic variants.ConclusionsFor GWAS, both lineage-specific and -combined analyses are useful, whereas PhyC may perform better in contexts of greater diversity. Unique associations with XDR in lineage-specific analyses provide evidence of diverging evolutionary trajectories between lineages 2 and 4 in response to antimicrobial drug therapy.

Compliance of antimicrobial drug therapy in patients with dental periapical abscess

Background: Dentist use of antimicrobial agents is characterized by a number of particularities. In effect, antibiotic prescription is empirical. Non-compliance to the prescribed medication can lead to the failure of the treatment. It should be noted that treatment failure can also result from several factors, but non-compliance can be considered the most critical factor. Aims and Objectives: The aim of the study was to assess the compliance with the full course of antibiotics as prescribed by a health-care provider to treat periapical abscess. Materials and Methods: A prospective, observational study was conducted to examine the prevalence of drug non-compliance. A total of 30 patients of any gender and age more than 16 years who attended outpatient department. Baseline information related to personal details, disease and drug therapy were recorded using a structured case record form. Compliance to therapy was evaluated by pill count adherence ratio (PCAR). Results: Most of the patients (73.33%) were compliant to antibiotic therapy. Males were more non-compliant antibiotic therapy as compared to females. Maximum patients (13.33%) with non-compliance to antibiotic therapy belong to the age group of 35–56 years. Patients with school level of education or below have maximum number of patients with non-compliance. Disappearance of symptoms and fear of side- effects of antibiotics are the commonest reasons for non-compliance. Mean value of PCAR was 0.89 ± 0.23. Conclusion: The result of our study shows that around 70% of patients were complying with the full course of antibiotics as prescribed. Therefore, health workers should make more effort to enhance the proper use of antibiotics in our population.

Testing for Coccidioidomycosis among Community-Acquired Pneumonia Patients, Southern California, USA1

We conducted a cohort study to identify characteristics associated with testing for, and testing positive for, coccidioidomycosis among patients with community-acquired pneumonia in southern California, USA. Limited and delayed testing probably leads to underdiagnosis among non-Hispanic black, Filipino, or Hispanic patients and among high-risk groups, including persons in whom antimicrobial drug therapy has failed.

Therapeutic Opportunities in Eukaryotic Translation.

The ability to block biological processes with selective small molecules provides advantages distinct from most other experimental approaches. These include rapid time to onset, swift reversibility, ability to probe activities in manners that cannot be accessed by genetic means, and the potential to be further developed as therapeutic agents. Small molecule inhibitors can also be used to alter expression and activity without affecting the stoichiometry of interacting partners. These tenets have been especially evident in the field of translation. Small molecule inhibitors were instrumental in enabling investigators to capture short-lived complexes and characterize specific steps of protein synthesis. In addition, several drugs that are the mainstay of modern antimicrobial drug therapy are potent inhibitors of prokaryotic translation. Currently, there is much interest in targeting eukaryotic translation as decades of research have revealed that deregulated protein synthesis in cancer cells represents a targetable vulnerability. In addition to being potential therapeutics, small molecules that manipulate translation have also been shown to influence cognitive processes such as memory. In this review, we focus on small molecule modulators that target the eukaryotic translation initiation apparatus and provide an update on their potential application to the treatment of disease.

Vasopressors in Sepsis.

Sepsis accounts for 10% of intensive care unit admissions and significant healthcare costs. Although the mortality rate from sepsis has been decreasing with better critical care, early identification of septic patients, and prompt interventions, the mortality rate remains 20%-30%. Review of the English-language literature. Norepinephrine is the first-line vasopressor in shock and is associated with a lower mortality rate as well as fewer adverse effects. Dopamine has similar actions but is associated with significantly more tachydysrhythmias and should be reserved for patients with bradycardia. Epinephrine and vasopressin are appropriate second-line vasopressors and may enable use of lower doses of norepinephrine while improving hemodynamics. Inotropes may be added in patients with cardiac dysfunction. Appropriate treatment of sepsis includes prompt identification, early antimicrobial drug therapy, appropriate fluid resuscitation, and initiation of vasopressors in the presence of continued septic shock. Further research needs to be done to better understand the ideal timing of the addition of a second agent and the optimal combinations of vasopressors for individual patients.

Clinical Decision Support Improves Adherence to Pediatric Antimicrobial Renal Dosing Guidelines

Background Antimicrobial drug dosage selection requires consideration of patient demographics, renal function, and indication(s) of use. We developed a strategy that employed upfront passive dose-guidance clinical decision support (CDS) in addition to noninterruptive/interruptive maximum dose warnings to guide providers to order renally appropriate antimicrobial drug therapy. Objectives Our objective was to assess the impact of passive dose-guidance CDS, along with a successive CDS strategy that provided renal dosing assistance at multiple points throughout order entry, on provider adherence to pediatric antimicrobial dosing guidelines. Methods A single-center, observational, retrospective cohort study at an academic pediatric hospital. The study compared the proportion of orders adherent to the institutional guidelines across three time points: a historical control (October 2014 to March 2015), phase I implementation (March 2015 to May 2015), and phase II implementation (May 2015 to October 2015). Results The proportion of adherent orders with respect to dose and frequency was 74% in the control period, 76% (odds ratio [OR] = 1.11; 95% confidence interval [CI], 0.76–1.16, p = 0.6) in phase I of the study, and increased to 81% (OR = 1.54; 95% CI, 1.16–2.03, p = 0.003) in phase II of the study. Conclusion Provider adherence to institutional antimicrobial dosing guidelines improved following the implementation of a successive CDS combining passive and noninterruptive/interruptive approaches. This study displays the value of designing CDS that occurs at multiple points within ordering workflow and minimizes intrusiveness. Our CDS strategy can be considered for implementation by other institutions using similar electronic health record systems.

Candidemia with Prosthetic Aortic Graft: Case Report

Infections of prosthetic aortic grafts status post-acute aortic dissection with Candida albicans (C. albicans) are rare. The gold standard of treatment for aortic graft infection is a combination of surgical resection and lifelong antimicrobial drug therapy, however postoperative mortality rates remain high. Here we present a 44-year-old man who presented with 2 months of fever, painful microembolic lesions localized to his right hypothenar eminence, right conjunctival hyperemia, right neural hearing loss, and a systolic murmur radiating from the aorta towards the neck. C. albicans was isolated from 3 separate blood cultures. Computed tomography (CT) displayed distinct thrombotic material affixed to the aortic prosthetic graft in the brachiocephalic artery. The patient was then treated with intravenous (IV) fluconazole for 8 weeks. During the treatment period, the patient suffered from brain hemorrhage in the right temporal lobe, presenting with hemiparalysis. After 8 weeks on IV fluconazole, oral fluconazole was then administered. Through 12 months of follow up, he remained asymptomatic, lab values only notable for slightly elevated inflammatory markers. This case suggests that for some patients, either unwilling or unable to endure surgery, candidemia associated with a prosthetic graft can be managed conservatively, with antifungal therapy alone.