Antibiotic Treatment Options Research Articles

Impact of an interactive, clinical decision-making workshop on student learning of antimicrobial stewardship principles

Background and purposeEducational escape room activities are being implemented in various classroom environments to augment learning. These games are structured in a linear pathway, and all participants must complete riddles to arrive at the same answer and “escape the room.” Educational activity and settingInvestigators created a multi-directional interactive learning activity where students were presented with a patient case. The activity required students to identify the presented infectious disease, interpret microbiology results, and select antibiotic treatment options. Students were required to provide dosing and antimicrobial stewardship metrics based on their treatment selection along with rationale. Upon completion of the activity, students participated in group discussions explaining the reasoning behind their selected treatment option. They also completed a satisfaction survey. Knowledge of antimicrobial stewardship principles was assessed via a multiple-choice exam. Exam performance was compared to the prior year when a traditional lecture format was utilized to teach the topic. FindingsOf 194 students enrolled in the course, 138 completed the satisfaction survey. The majority (86.9%) indicated that they would recommend the activity and 88.2% considered it an effective tool for learning antimicrobial stewardship. There was a mean decline of 6.38% (P = .3) in correctly answered exam questions with the implementation of the activity compared to results from the previous academic year (N = 185). SummaryStudents perceived the game as a valuable learning experience, but it did not result in an improvement in knowledge of antimicrobial stewardship as assessed by multiple-choice exams.

Efficacies of Colistin-Carbapenem versus Colistin-Tigecycline in Critically Ill Patients with CR-GNB-Associated Pneumonia: A Multicenter Observational Study.

Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC (n = 62) and CT (n = 59) groups. After propensity score matching (n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria (p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients.

Challenges to Early Discharge of Patients with Upper Urinary Tract Infections by ESBL Producers: TMP/SMX as a Step-Down Therapy for Shorter Hospitalization and Lower Costs.

BackgroundUrinary tract infections (UTIs) caused by extended spectrum beta-lactamase (ESBL) producing pathogens have increased and are treated with carbapenem in general. Carbapenem use is associated with prolonged hospitalization or daily outpatient visit. The aim of this study was to investigate patients with UTIs by ESBL-producing pathogens for early discharge using an old oral antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), which is susceptible to ESBL-producing pathogens.MethodsData on UTIs caused by ESBL-producing pathogens from a single tertiary hospital were collected retrospectively. Patients who had been treated with intravenous carbapenems or oral TMP/SMX were included. Patients’ clinical and microbiological outcomes were compared between oral TMP/SMX and ertapenem treatment groups.ResultsA total of 103 patients were included, 21 of whom had been treated with TMP/SMX, whereas 82 with ertapenem. Clinical outcomes between the two groups were not significantly different (TMP/SMX: 90.5%; ertapenem: 84.1%, p = 0.73). The microbiological cure rate was higher in the TMP/SMX group than in the ertapenem group (90.5% vs 58.5%, respectively, p = 0.01). The mean duration of hospitalization was significantly shorter in the TMP/SMX group than in the ertapenem group (8.00 ± 10.50 days vs 14.00 ± 37.00 days, p = 0.07). The mean duration of antibiotic treatment was longer in the ertapenem group than in the TMP/SMX group (16.45 ± 4.77 vs 12.76 ± 5.37 days, p = 0.006).ConclusionFor susceptible pathogens, TMP/SMX may enable early discharge as an effective oral antibiotic treatment option for UTIs caused by ESBL-positive pathogens. Additionally, use of oral antibiotics can shorten hospital stays and reduce medical costs.

Divergent synthesis and biological evaluation of 2-(trifluoromethyl)pyridines as virulence-attenuating inverse agonists targeting PqsR

A short and divergent route towards new derivatives of 2-(trifluoromethyl)pyridines as potent inverse agonists of the bacterial target PqsR against Pseudomonas aeruginosa (PA) infections is described. This Gram-negative pathogen causes severe nosocomial infections and common antibiotic treatment options are rendered ineffective due to resistance issues. Based on an earlier identified optimized hit, we conducted derivatization and rigidification attempts employing two central building blocks. The western part of the molecule is built up via a 2-(trifluoromethyl)pyridine head group equipped with a terminal alkyne. The eastern section is then introduced through aryliode motifs exploiting Sonogashira as well as Suzuki-type chemistry. Subsequent modification provided quick access to an array of compounds, allowed for deep SAR insights, and enabled to optimize the hit scaffold into a lead structure of nanomolar potency combined with favorable in vitro ADME/T features.

\u201cOPTIONS-DC\u201d, a feasible discharge planning conference to expand infection treatment options for people with substance use disorder

BackgroundSerious bacterial infections associated with substance use often result in long hospitalizations, premature discharges, and high costs. Out-of-hospital treatment options in people with substance use disorder (SUD) are often limited.MethodsWe describe a novel multidisciplinary and interprofessional care conference, “OPTIONS-DC,” to identify treatment options agreeable to both patients and providers using the frameworks of harm reduction and patient-centered care. We retrospectively reviewed charts of patients who had an OPTIONS-DC between February 2018 and July 2019 and used content analysis to understand the conferences’ effects on antibiotic treatment options.ResultsFifty patients had an OPTIONS-DC during the study window. Forty-two (84%) had some intravenous (IV) substance use and 44 (88%) had an active substance use disorder. Participants’ primary substances included opioids (65%) or methamphetamines (28%). On average, conferences lasted 28 min. OPTIONS-DC providers recommended out-of-hospital antibiotic treatment options for 34 (68%) of patients. OPTIONS-DC recommended first line therapy of IV antibiotics for 35 (70%) patients, long-acting injectable antibiotics for 14 (28%), and oral therapy for 1 (2%). 35 (70%) patients that had an OPTIONS-DC completed an antibiotic course and 6 (12%) left the hospital prematurely. OPTIONS-DC expanded treatment options by exposing and contextualizing SUD, psychosocial risk and protective factors; incorporating patient preferences; and allowing providers to tailor antibiotic and SUD recommendations.ConclusionsOPTIONS-DC is a feasible intervention that allows providers to integrate principles of harm reduction and offer patient-centered choices among patients needing prolonged antibiotic treatment.

The Synergistic Activity and Optimizing Doses of Tigecycline in Combination with Aminoglycosides against Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates.

Carbapenem-resistant Enterobacteriaceae (CRE), especially carbapenem-resistant Klebsiella pneumoniae (CRKP), are among the largest pathogenic threats to humans. The available antibiotic treatment options for combating CRKP are limited. Colistin-resistant Enterobacteriaceae (CoRE) have also been reported worldwide, including in Thailand. Therefore, this study aimed (1) to determine minimum inhibitory concentrations (MICs) and synergistic activities of antibiotics of CRKP, and (2) to determine the probability target of attainment (PTA) and cumulative fraction of response (CFR) using pharmacokinetic/pharmacodynamic (PK/PD) data. Clinical CRKP isolates were obtained from Phramongkutklao Hospital (June to November 2020). Broth microdilution and checkerboard techniques were used to determine the mono- and synergistic activities of antibiotics. Carbapenemase and mcr-1 genes were also identified by polymerase chain reaction (PCR). The optimal antibiotic regimens were evaluated using Monte Carlo simulations. Forty-nine CRKP isolates were collected, 40 of which were CoRKP strains. The MIC50 and MIC90 of tigecycline, amikacin, and gentamicin were 1 and 2 µg/mL, 4 and 16 µg/mL, and 0.25 and 4 µg/mL, respectively. None of any isolates expressed the mcr-1 gene, whereas blaOXA-48 (53.1%) and blaOXA-48 plus blaNDM (42.9%) were detected. Synergistic activity was observed in 8.2% of isolates for tigecycline combined with amikacin or gentamicin. Additive activity was observed in 75.5% of isolates for tigecycline-amikacin and 69.4% for tigecycline-gentamicin, and no antagonism was observed. High-dose antibiotic regimens achieved the PTA target. The general recommended dose of combination regimens began with 200 mg tigecycline and 25 mg/kg amikacin, or 7 mg/kg gentamicin, followed by 100 mg tigecycline every 12 h and 15 mg/kg amikacin or 5 mg/kg gentamicin every 24 h. In conclusion, tigecycline plus aminoglycosides might be a potential regimen against CRKP and CoRKP. The appropriate combination regimen based on MIC-based dose adjustment can improve optimal antibiotic dosing. Further research via clinical studies will be necessary to confirm these results.

The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent.

The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.

Carbapenems for the Treatment of Pneumonia: A literature review regarding resistance, risk factors, and mortality

Carbapenem is one of antibiotic to treat respiratory infections such as pneumonia that frequently used in tertiary care facilities and started to create resistances. This study aims to review the resistance of carbapenems, assess the risk factors for resistance that leads to mortality, and the more effective antibiotic treatment options to overcome the resistance. Assessment of the use of carbapenems in pneumonia through previous studies were carried out by searching the articles in search engine databases in 2011 to 2021. Articles reporting carbapenems resistance, risk factors, and mortality were selected based on inclusion and exclusion criteria. Of 14 articles included in inclusion criteria, 4 studies reported the occurrence of resistance to gram-negative bacteria such as Acinetobacter aumanii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and 10 articles reported risk factors and mortality. The risk factors for carbapenems resistance are the history of carbapenems use, duration of hospitalization, use of mechanical ventilation, high Simplified Acute Physiology Score (SAPS) scores, and high Acute Physiologic and Chronic Health Evaluation (APACHE). Carbapenems resistance causes mortality such as septic shock, high Sequential Organ Failure Assessment (SOFA) scores, and elevated risk at > 60 years of age, female sex, and inappropriate choice of antibiotics. The results showed that imipenem has higher resistance than other carbapenems members, the risk factors for carbapenems resistance are dominated by a history of carbapenems use, mortality caused by high score SOFA, and colistin can be the current choice to overcome carbapenems resistance.

Urinary Tract Infections are becoming Multi-drug Resistant due to Extended Spectrum Beta-lactamases-producing Klebsiella pneumonia

Introduction: Klebsiella pneumoniae are among the most common cause of urinary tract infections such as cystitis and pyelonephritis. These multi-drug resistant K. pneumoniae are producers of extended spectrum beta-lactamases (ESBL) that are capable of hydrolyzing beta-lactams and non-beta-lactams. This laboratory-based study sought to establish the increase of ESBL-producing K. pneumoniae in multi-drug resistant urinary tract infections and determine the effective antibiotic treatment options.
 Methods: One hundred and seventy five K. pneumoniae isolates obtained from urine cultures were randomly collected and the combined disc synergy method was used to determine the ESBL-producing K. pneumoniae. The Vitek 2 system (bioMérieux, France) was used to perform antimicrobial susceptibility testing of 17 commonly used antibiotics. The data from the work was collated and statistically analysed using the chi-square test and Mann-Whitney U test. P values < 0.05 were considered significant.
 Results: Of the 175 K. pneumoniae responsible for urinary tract infections, 73.7% were producing ESBL suggesting that most urinary tract infections caused by K. pneumoniae will be multi-drug resistant. The antimicrobial resistance differences between ESBL-producing and non-ESBL-producing Klebsiella pneumoniae indicated a significance difference with p < 0.05. This study indicated that imipenem and amikacin are the antibiotic of choice for the treatment of multi-drug resistant urinary tract infections caused by ESBL-producing K. pneumoniae. Cephalosporins and nitrofurantoin are suitable for the treatment of urinary tract infections due to non-ESBL-producing K. pneumoniae.
 Conclusion: This study indicated that imipenem (carbapenem) and amikacin are the antibiotic of choice for the treatment of multi-drug resistant urinary tract infections caused by ESBL-producing K. pneumoniae. The third and fourth generation cephalosporins and nitrofurantoin are suitable for the treatment of urinary tract infections due to non-ESBL-producing K. pneumoniae. Rational use of antibiotics and evidence based antibiotic prescription will help to control the spread of resistance by ESBL-producing K. pneumoniae. There is the need to intensify research in the use of natural products to treat multi-drug resistant urinary tract infections emanating from ESBL-producing K. pneumoniae

First detection of a plasmid-encoded New-Delhi metallo-beta-lactamase-1 (NDM-1) producing Acinetobacter baumannii using whole genome sequencing, isolated in a clinical setting in Benin

BackgroundCarbapenem-resistant Acinetobacter baumannii is considered a top priority pathogen by the World Health Organization for combatting increasing antibiotic resistance and development of new drugs. Since it was originally reported in Klebsiella pneumoniae in 2009, the quick spread of the blaNDM-1 gene encoding a New-Delhi metallo-beta-lactamase-1 (NDM-1) is increasingly recognized as a serious threat. This gene is usually carried by large plasmids and has already been documented in diverse bacterial species, including A. baumannii. Here, we report the first detection of a NDM-1-producing A. baumannii strain isolated in Benin.Case presentationA 31-year-old woman was admitted to a surgical unit with a diagnosis of post-cesarean hematoma. An extensively-drug resistant A. baumannii strain solely susceptible to amikacin, colistin and ciprofloxacin, and resistant to several other antibiotics including ceftazidime, imipenem, meropenem, gentamicin, tobramycin, ceftazidime/avibactam, and sulfamethoxazole-trimethoprim, was isolated from the wound. Production of NDM-1 was demonstrated by immunochromatographic testing. Whole genome sequencing of the isolate confirmed the presence of blaNDM-1, but also antibiotic resistance genes against multiple beta-lactamases and other classes of antibiotics, in addition to several virulence genes. Moreover, the blaNDM-1 gene was found to be present in a Tn125 transposon integrated on a plasmid.ConclusionsThe discovery of this extensively-drug resistant A. baumannii strain carrying blaNDM-1 in Benin is worrying, especially because of its high potential risk of horizontal gene transfer due to being integrated into a transposon located on a plasmid. Strict control and prevention measures should be taken, once NDM-1 positive A. baumannii has been identified to prevent transfer of this resistance gene to other Enterobacterales. Capacity building is required by governmental agencies to provide suitable antibiotic treatment options and strategies, in combination with strengthening laboratory services for detection and surveillance of this pathogen.

1378. Reservoirs of Transmission of Resistant Gram-negative Pathogens Responsible for Neonatal Sepsis among Hospitalized Neonates in Pune, India

BackgroundNeonatal infections with resistant Gram-negative (GN) organisms are associated with high rates of mortality, with limited antibiotic treatment options. The role of maternal colonization and environmental GN organisms as reservoirs for transmission to neonates has not been well described.MethodsWe performed a prospective cohort study from October 12, 2018, until October 31, 2019, to describe the role of maternal and environmental GN colonization in BSI among neonates admitted to the neonatal intensive care unit (NICU) at a tertiary care center in Pune, India. Women admitted to Labor & Delivery with risk factors for neonatal sepsis who provided consent were enrolled and their neonates were followed until hospital discharge. For neonates who developed bloodstream infection (BSI), colonization with resistant GN organisms was assessed in their mothers from frozen vaginal and rectal swabs collected at enrollment and at delivery and in the neonates from frozen skin swabs and peri-rectal swabs collected at day of life (DOL) 0, 3, 7, and weekly until discharge. Environmental colonization was assessed with weekly sampling of unit sinks and the immediate neonatal care environment. Colonization samples were processed to identify organisms that matched neonatal blood culture isolates.Results953 women were enrolled, of whom 741 (78%) received antepartum antibiotics. Among 987 live born neonates, 12 (1%) died in the delivery room and 257 (26%) required NICU admission. Among neonates admitted to the NICU, 143 (56%) had at least one blood culture, of which 28 (20%) were positive; 21 (75%) had a GN BSI. The most common cause of neonatal BSI was Klebsiella pneumoniae, and 8 (38%) GN BSI were due to a carbapenem-resistant organism. No organism isolated from maternal samples matched organism and resistance pattern from neonatal blood culture. Matching strains were found in unit sinks and neonatal rectal and skin samples (Figure 1).Organism recovery from swabs and match to bloodstream isolate by sample source and time of collection from birth ConclusionAmong neonates born to mothers with risk factors for neonatal sepsis, GN organisms were the most common cause of neonatal BSI. Environmental and neonatal colonization may represent important reservoirs of transmission for these pathogens among neonates hospitalized in a tertiary care NICU in Pune, India.Disclosures All Authors: No reported disclosures

Molecular characterization of fluoroquinolone resistant Escherichia coli from Ghana

Background: The indiscriminate use of antibiotics in humans and animals has led to an increase in drug resistant bacteria. This has become a global health threat and a limitation to first- and second-line antibiotic treatment options with consequences including treatment failure and higher medical cost. Using Escherichia coli (E. coli) as an indicator of resistant bacteria, the study sought to determine the distribution of antibiotic resistant isolates from clinical samples and characterize quinolone-resistant genes. Methods and materials: Methods: An experimental quantitative approach was adopted to obtain clinical samples followed by strain identification and antimicrobial susceptibility testing. E-tests were used to determine the Minimum Inhibitory Concentration (MIC) for ciprofloxacin resistant isolates after which chromosomal DNA and plasmids were extracted and probed for the genes (gyr A, parC, aac(6′)1bcr gyr B, Qnr A, Qnr B, Qnr C, Qnr S, qep A and oqx B) known to confer ciprofloxacin–resistance. The amplicons were sequenced and analyzed for mutational hot spots. Results: In total, 47/83 (56.6%) E. coli isolates were resistant to ciprofloxacin and 29/47 (61.7%) showed MIC > 32 μg/mL. Majority 21/29 (72.4%) of the ciprofloxacin resistant E. coli were positive for Gyr A and mutations were found within codon 83 and 87. In parC, the mutations were at codons 71 and 80. Conclusion: The study revealed a high prevalence of fluoroquinolone resistance and found chromosomal and plasmid mediated genes to be widespread and linked to ciprofloxacin-resistance in Ghana. The putative mutations in Quinolone Resistance Determining Regions (QRDR) and the new mutations identified in parC requires further investigations into its association with ciprofloxacin-resistant E. coli. However the preliminary data justifies the need for intensified surveillance in Ghana.

Vitamin E as promising adjunct treatment option in the combat of infectious diseases caused by bacterial including multi-drug resistant pathogens - Results from a comprehensive literature survey.

The use of antibiotics has provoked an emergence of various multidrug-resistant (MDR) bacteria. Infectious diseases that cannot be treated sufficiently with conventional antibiotic intervention strategies anymore constitue serious threats to human health. Therefore, current research focus has shifted to alternative, antibiotic-independent therapeutic approaches. In this context, vitamin E constitutes a promising candidate molecule due to its multi-faceted modes of action. Therefore, we used the PubMed database to perform a comprehensive literature survey reviewing studies addressing the antimicrobial properties of vitamin E against bacterial pathogens including MDR bacteria. The included studies published between 2010 and 2020 revealed that given its potent synergistic antimicrobial effects in combination with distinct antibiotic compounds, vitamin E constitutes a promising adjunct antibiotic treatment option directed against infectious diseases caused by MDR bacteria such as Pseudomonas aeruginosa, Burkholderia cenocepacia and methicillin-resistant Staphylococcus aureus (MRSA). In conclusion, the therapeutic value of vitamin E for the treatment of bacterial infections should therefore be investigated in future clinical studies.

Aortic Prosthesis-Associated MDR Pseudomonas Infections as a Diagnostic and Therapeutic Challenge

Endovascular prostheses are used to treat life-threatening conditions such as ruptured aortic aneurysms. Prosthetic infection cause significant morbidity and mortality, posing important diagnostic and therapeutic challenges. It is particularly difficult to diagnose and, in the era of multidrug resistance (MDR), these type of infections may become even more difficult to treat. Herein, we reported a case of a secondary prosthetic endovascular infection following repeated bacteremia episodes from a urinary source. This case illustrates an MDR Pseudomonas aeruginosa aortic infection that was difficult to diagnose with no oral antibiotic treatment options.

Molecular characterization of invasive Enterobacteriaceae from pediatric patients in Central and Northwestern Nigeria.

BackgroundBacteremia is a leading cause of mortality in developing countries, however, etiologic evaluation is infrequent and empiric antibiotic use not evidence-based. Here, we evaluated the patterns of ESBL resistance in children enrolled into a surveillance study for community acquired bacteremic syndromes across health facilities in Central and Northwestern Nigeria.MethodBlood culture was performed for children aged less than 5 years suspected of having sepsis from Sept 2008-Dec 2016. Blood was incubated using the BACTEC00AE system and Enterobacteriacea identified to the species level using Analytical Profile Index (API20E®). Antibiotic susceptibility profile was determined by the disc diffusion method. Real time PCR was used to characterize genes responsible for ESBL production.ResultOf 21,000 children screened from Sept 2008-Dec 2016, 2,625(12.5%) were culture-positive. A total of 413 Enterobacteriaceae available for analysis were screened for ESBL. ESBL production was detected in 160 Enterobacteriaceae, high resistance rates were observed among ESBL-positive isolates for Ceftriaxone (92.3%), Aztreonam (96.8%), Cefpodoxime (96.3%), Cefotaxime (98.8%) and Trimethoprim/sulfamethoxazole (90%), while 87.5%, 90.7%, and 91.9% of the isolates were susceptible to Imipenem, Amikacin and Meropenem respectively. Frequently detected resistance genes were blaTEM—83.8% (134/160), and, blaCTX-M 83.1% (133/160) followed by blaSHVgenes 66.3% (106/160). Co-existence of blaCTX-M, blaTEM and blaSHV was seen in 94/160 (58.8%), blaCTX-M and blaTEM in 118/160 (73.8%), blaTEM and blaSHV in 97/160 (60.6%) and blaCTX-M and blaSHV in 100/160 (62.5%) of isolates tested.ConclusionOur results indicate a high prevalence of bacteremia from ESBL Enterobacteriaceae in this population of children. These are resistant to commonly used antibiotics and careful choice of antibiotic treatment options is critical. Further studies to evaluate transmission dynamics of resistance genes could help in the reduction of ESBL resistance in these settings.

Discourse-directed framing as communication strategy alters students’ concept of antibiotics and antibiotic resistance formation

ABSTRACT One of the most urgent matters in current medicine is the preservation of antibiotic treatment options due to an increasing threat of antibiotic resistance in pathogenic microorganisms. Therefore, increasing awareness by adapted science education and communication regarding this topic is of the utmost importance. This article shows that an out-of-school laboratory course using active learning techniques is a valuable contribution to traditional teaching inciting personal and social responsibility. Attitude toward science (BRAINS), value of science to society (MATS), situational interest and emotions were tested. The participants’ conception of antibiotics was evaluated by analysing follow-up mind maps. Generally, the laboratory course created positive feelings and situational interest. Compared to an instructor-directed frame, communication within an individually adapting discourse-directed frame conveyed more wide-spread perception of the topic, including societal and personal implications. The outcome of the study provides evidence that an out-of-school laboratory course can be a valuable tool for interest development in socio-scientific issues. Discourse-directed framing, in this environment, improves the individual ability to alter social and personal responsibility regarding science topics.

Epidemiology of NDM-Producing Enterobacteriaceae in Michigan

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are classified as an urgent antibiotic-resistant threat by the CDC, and they are listed on the critical priority list by the World Health Organization due to the lack of antibiotic treatment options. New-Delhi metallo-β-lactamase (NDM) is an emerging mechanism of carbapenem resistance in the United States. We sought to understand the risk factors and clinical characteristics of patients with NDM CRE in Michigan to improve surveillance. Methods:A retrospective descriptive study was conducted in collaboration with the Michigan Department of Health and Human Services (MDHHS). CRE isolates submitted to MDHHS between April 2014 and July 2019 were tested for the presence of NDM using CDC PCR protocols. Additional information on case demographics, laboratory results, healthcare and antibiotic exposure history, and travel history were collected. Results: In total, 30 NDM cases were identified in Michigan during the study period. Of these 30 cases, 15 (50%) were men, and the median age was 73.5 years (range, 20–88 20). Also, 2 of these patients (6.6%) were immunocompromised; 2 patients (6.6%) had had extensive abdominal surgery, and 2 patients (6.6%) had recurrent hospitalization. Furthermore, 12 case isolates (40%) were collected in outpatient settings, whereas 16 (53%) were collected from inpatient settings. In addition, 13 (43%) patients were admitted from home and 4 (13%) presented from an extended-care facility. Urine was the most common site of isolation in 19 of 30 (63%) cases, followed by blood and tissue culture in 4 of 30 (13%) each. Escherichia coli was the most common organism (17 of 30, 57%), followed by Klebsiella pneumoniae (9 of 30, 30%). Also, 15 of 30 cases (50%) had a recent history of international travel, and of these, 9 of 15 (60%) reported travel to India. Among these 15 cases, 12 (80%) sought medical care in the countries they visited. Two cases (6.6%) had a documented history of multidrug-resistant organism colonization or infection. The mortality rate was 6.6% (2 of 30). The mean time from admission to implementation of contact precautions was 7.3 days (range, 0–20). Conclusions: Suspicion of NDM CRE strains should remain high in patients with a travel history from areas known as major reservoirs of NDM. Delay in implementing contact precautions, as noted in the present study, can lead to a greater risk of transmission. Early detection and subsequent isolation of NDM patients are essential strategies for preventing transmission within healthcare facilities. Future efforts include performing whole-genome sequencing of these isolates to assist in identifying potential epidemiological links among the affected patients.Funding: NoneDisclosures: None

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance.

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii.

Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro.

Chronic wounds are a prominent concern, accounting for $25 billion of health care costs annually. Biofilms have been implicated in delayed wound closure, but they are susceptible to developing antibiotic resistance and treatment options continue to be limited. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of a therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side effects. We hypothesize that the hydrogel can provide controlled elution of antibiotics leading to inhibition of bacterial growth and disruption of biofilm formation. The rate of antibiotic elution from the collagen-rich hydrogel and the efficacy of biofilm disruption was assessed with Pseudomonas aeruginosa Bacterial growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified using in vitro models. The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 h at therapeutic levels. The treatment inhibited bacterial growth and disrupted biofilm formation at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cells. The antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release effective for bacteria cell death without native cell death. A human-derived hydrogel that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.

Antibiotic Multidrug Resistance of Escherichia coli Causing Device- and Procedure-related Infections in the United States Reported to the National Healthcare Safety Network, 2013-2017.

Escherichia coli is one of the most common causes of healthcare-associated infections (HAIs); multidrug resistance reduces available options for antibiotic treatment. We examined factors associated with the spread of multidrug-resistant E. coli phenotypes responsible for device- and procedure-related HAIs from acute care hospitals, long-term acute care hospitals, and inpatient rehabilitation facilities, using isolate and antimicrobial susceptibility data reported to the National Healthcare Safety Network during 2013-2017. We used multivariable logistic regression to examine associations between co-resistant phenotypes, patient and healthcare facility characteristics, and time. We also examined the geographic distribution of co-resistant phenotypes each year by state and by hospital referral region to identify hot spots. A total of 96 672 E. coli isolates were included. Patient median age was 62 years, and 60% were female; more than half (54%) were reported from catheter-associated urinary tract infections. From 2013 to 2017, 35% of the isolates were nonsusceptible to fluoroquinolones (FQs), 17% to extended-spectrum cephalosporins (ESCs), and 13% to both ESCs and FQs. The proportion of isolates co-resistant to ESCs and FQs was higher in 2017 (14%) than in 2013 (11%) (P < .0001); overall prevalence and increases were heterogeneously distributed across healthcare referral regions. Co-resistance to FQs and ESCs was independently associated with male sex, central line-associated bloodstream infections, long-term acute care hospitals, and the 2016-2017 (vs 2013-2014) reporting period. Multidrug resistance among E. coli causing device- and procedure-related HAIs has increased in the United States. FQ and ESC co-resistant strains appear to be spreading heterogeneously across hospital referral regions.