Antibiotic Resistance Review PDF

Journal of Infection and Public Health (2017) 10, 369—378 REVIEW Antibiotic resistance Marianne Frieri a,∗, Krishan Kumar b,1, Anthony Boutin c,1 a Division of Allergy Immunology, Department of Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, United Stat...

Journal of Infection and Public Health (2017) 10, 369—378 REVIEW Antibiotic resistance Marianne Frieri a,∗, Krishan Kumar b,1, Anthony Boutin c,1 a Division of Allergy Immunology, Department of Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, United States b Division of Pediatric, Department of Emergency Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, United States c Adult Emergency Medicine, Department of Emergency Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, United States Received 21 May 2016; accepted 4 August 2016 KEYWORDS Summary Antimicrobial resistance in bacterial pathogens is a challenge that is Antibiotic resistance; associated with high morbidity and mortality. Multidrug resistance patterns in Gram- Biofilms; positive and -negative bacteria are difficult to treat and may even be untreatable Infections; with conventional antibiotics. There is currently a shortage of effective therapies, Public health; lack of successful prevention measures, and only a few new antibiotics, which Emergency require development of novel treatment options and alternative antimicrobial ther- apies. Biofilms are involved in multidrug resistance and can present challenges for Department infection control. Virulence, Staphylococcus aureus, Clostridium difficile infection, vancomycin-resistant enterococci, and control in the Emergency Department are also discussed. © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Limited. All rights reserved. Contents Introduction...................................................................................................370 Antibiotic resistance......................................................................................370 Biofilms...................................................................................................371 Virulence and S. aureus...................................................................................373 Emergency Department...................................................................................375 Clostridium difficile infection.............................................................................375 ∗ Corresponding author at: Nassau University Medical Center, Department of Medicine, 2201 Hempstead Turnpike, East Meadow, NY 11554, United States. Fax: +1 516 572 5609. E-mail addresses: [email protected] (M. Frieri), [email protected] (K. Kumar), [email protected] (A. Boutin). 1 Fax: +1 516 572 5465. http://dx.doi.org/10.1016/j.jiph.2016.08.007 1876-0341/© 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Limited. All rights reserved. 370 M. Frieri et al. Vancomycin-resistant enterococci........................................................................ 376 Control in the Emergency Department.................................................................... 376 Conclusion.................................................................................................... 377 Funding....................................................................................................... 377 Competing interests...........................................................................................377 Ethical approval...............................................................................................377 References.................................................................................................... 377 Introduction an alarming rate. There are challenges in the combat of bacterial infections and accompanied Antibiotic resistance diseases and the current shortage of effective drugs, lack of successful prevention measures This study discusses the impact of antibiotic resis- and only a few new antibiotics in the clinical tance as a persistent, global health threat and pipeline will require the development of novel highlights efforts to improve this complex problem treatment options and alternative antimicrobial. Political agendas, legislation, development of therapies. The authors stated that increas- therapies and educational initiatives are essential ing understanding of bacterial virulence strategies to mitigate the increasing rate of antibiotic resis- and induced molecular pathways of the infec- tance. Prescribers, policymakers and researchers tious disease provides novel opportunities to target are charged with the complex task of mitigating and interfere with crucial pathogenicity factors or antibiotic resistance in an era when new treat- virulence-associated traits of the bacteria while ments for bacterial infections are limited. The bypassing the evolutionary pressure on the bac- authors propose that monitoring, surveillance of terium to develop resistance. The authors took practice, policy and new treatments provide solu- a closer look at the bacterial virulence-related fac- tions to antibiotic resistance in both the human and tors and processes that present promising targets agricultural sectors. This article emphasizes the for anti-virulence therapies, recently discovered complexity of antibiotic resistance and highlights inhibitory substances, their promises and discussed the need for a multifaceted approach to improve the challenges and problems that need to be health care outcomes. faced. Antimicrobial resistance in bacterial pathogens Finding strategies against the development of is a worldwide challenge associated with high antibiotic resistance is a major global challenge morbidity and mortality. Multidrug resistant for the life sciences community and for public patterns in Gram-positive and -negative bacteria health. The past decades have seen a dramatic have resulted in difficult-to-treat or even untreat- worldwide increase in human-pathogenic bacteria able infections with conventional antimicrobials. that are resistant to one or multiple antibiotics Because the early identification of causative. More infections caused by resistant microorgan- microorganisms and their antimicrobial susceptibil- isms fail to respond to conventional treatment, and ity patterns in patients with bacteremia and other even last-resort antibiotics have lost their power. serious infections is lacking in many healthcare In addition, industry pipelines for the develop- settings, broad spectrum antibiotics are liber- ment of novel antibiotics have run dry over the ally and mostly unnecessarily used. Dramatic past few decades. A recent World Health Day by increases in emerging resistance occurs and, when the WHO with the theme ‘‘Combat drug resis- coupled with poor infection control practices, resis- tance: no action today means no cure tomorrow’’ tant bacteria can easily be disseminated to the triggered an increase in research activity, and sev- other patients and the environment. Availability eral promising strategies have been developed to of updated epidemiological data on antimicro- restore treatment options against infections by bial resistance in frequently encountered bacterial resistant bacterial pathogens. pathogens will be useful not only for deciding The emergence and spread of antibiotic resis- on treatment strategies but also for devising an tance among pathogenic bacteria has been a effective antimicrobial stewardship program in hos- growing problem for public health in recent pitals. decades. It is becoming increasingly recognized Resistance of important bacterial pathogens to that not only antibiotic resistance genes (ARGs) common antimicrobial therapies and emergence encountered in clinical pathogens are of rele- of multidrug-resistant bacteria are increasing at vance, but rather, all pathogenic, commensal as Antibiotic resistance 371 well as environmental bacteria, mobile genetic on the effect of biocide exposure on the devel- elements and bacteriophages, form a reservoir opment of bacterial resistance to antimicrobials of ARGs (the resistome) from which pathogenic. Thus, such information should address the bacteria can acquire resistance via horizontal gene call from the U.S. FDA and European Union Bio- transfer (HGT). HGT has caused antibiotic cidal Products Regulation for manufacturers to resistance to spread from commensal and environ- provide information on antimicrobial resistance and mental species to pathogenic ones, as has been cross-resistance in bacteria after the use of their shown for some clinically important ARGs. While product. transformation and transduction are deemed less important, recent discoveries suggest their role Biofilms may be larger than previously thought. Under- standing the extent of the resistome and how its Pathogenic microbial biofilm is considered a world- mobilization to pathogenic bacteria takes place is wide challenge due to the inherent antibiotic essential for efforts to control the dissemination of resistance conferred by its lifestyle. By living these genes. The authors discussed the concept of in a community in a clinical situation, microbial the resistome, providing examples of HGT of clini- organisms are responsible for severe and danger- cally relevant ARGs and an overview of the current ous cases of infection. Combating this organization knowledge of the contributions the various HGT of cells usually requires high antibiotic doses for a mechanisms make to the spread of antibiotic resis- prolonged time, and these approaches often fail, tance. contributing to infection persistence. In addi- Multidrug-resistant bacteria have increased at tion to therapeutic limitations, biofilms can be an alarming rate over recent decades and cause a source of infections when they grow in med- serious problems. The emergence of resistant ical devices. The challenge imposed by biofilms infections caused by these bacteria has led to mor- has mobilized researchers in the entire world tality and morbidity and there is an urgent need to to propose or develop alternatives to control find solutions to combat bacterial resistance. In biofilms. The authors in this review summarized this paper, the authors discuss some mechanisms of the new frontiers that could be used in clinical antibiotic resistance such as changing the antibac- circumstances to prevent or eliminate pathogenic terial agent’s uptake and biofilm formation as well biofilms. as a wide range of approaches such as developing The treatment of biofilm infections with antibi- new generations of antibiotics, combination ther- otics remains a puzzle although progress on biofilm apy, natural antibacterial substances and applying research has been made. Past pharmacokinetic (PK) nanoparticulate systems. and pharmacodynamic (PD) profiles of an antimicro- In this study, the authors assessed the propen- bial agent provide important information helping sity of biocide exposure in the development of to establish an efficient dosing regimen and to bacterial antimicrobial resistance. Their proto- minimize the development of antimicrobial toler- col was based on reporting changes in established ance and resistance in biofilm infections. Most antimicrobial susceptibility profiles in biocides previous PK/PD studies of antibiotics have been and antibiotics during and after exposure to a performed on planktonic cells, and extrapolation product. Their results showed that exposure to tri- of the results on biofilms is problematic as bacterial closan (0.0004%) was associated with a high risk biofilms differ from planktonic grown cells in terms of developing resistance and cross-resistance in of growth rate, gene expression, and metabolism. Staphylococcus aureus and Escherichia coli but These authors set up several protocols for the stud- was not observed with exposure to chlorhexi- ies of PK/PD of antibiotics in biofilm infections of dine (0.00005%) or a hydrogen peroxide-based Pseudomonas aeruginosa in vitro and in vivo. It biocidal product (in during use conditions). should be underscored that none of the protocols Exposure to a low concentration of hydrogen per- in biofilms have yet been certificated for clinical oxide (0.001%) carried a risk of emerging resistance use or proved useful for guidance of antibiotic ther- to antibiotics if the presence of the oxidizing apy. agent was maintained. They observed a number The increase in multi-drug resistant P. aeruginosa of unstable clinical resistances to antibiotics after infections is a worldwide dilemma. At the heart of exposure to the cationic biocide and oxidizing the problem is the inability to treat established agent, notably to tobramycin and ticarcillin- P. aeruginosa biofilms with standard antibiotic clavulanic acid. Using a decision tree based on therapy, including fluoroquinolones. These the change in antimicrobial susceptibility test authors addressed a previously unstudied question results, they were able to provide information regarding the effect of the commonly prescribed 372 M. Frieri et al. calcium channel blocker (CCB) diltiazem on biofilm the development and the use of new and rapid growth. Real-time monitoring of the overall growth technologies is critical. The use of the next- and killing of P. aeruginosa biofilm during fluoro- generation sequencing platforms by microbiologists quinolone therapy in the presence and absence of and infectious disease specialists has allowed diltiazem was performed. The authors found that great progress in the medical field. These authors for P. aeruginosa biofilms, resistance to first-line reviewed the usefulness of whole-genome sequenc- fluoroquinolones may be induced by the commonly ing for the detection of virulence and antibiotic prescribed calcium channel blocker diltiazem. resistance-associated genes. The conventional in vitro models simulate phar- The importance of bacterial biofilms in chronic macodynamics of antibiotics in the treatment of wound pathogenesis is well established. Different planktonic P. aeruginosa. In this study, the authors treatment modalities, including topical dressings, proposed a novel pharmacodynamic model of have yet to show consistent efficacy against wound ofloxacin activity in the treatment of P. aeruginosa biofilms. This study evaluated the impact of a biofilm. novel, antimicrobial test dressing on P. aeruginosa Samples from the coupons and the central biofilm-infected wounds. Six-mm dermal punch compartment bioreactor (CCB) were assessed for wounds in rabbit ears were inoculated with 10(6) viability of the biofilm and shedding planktonic cells colony-forming units of P. aeruginosa. Biofilm over 24 h. Ofloxacin concentrations were assessed was established in vivo using our published model. in each sample withdrawn for the CCB using a bioas- Dressing changes were performed every other day say method. with either active control or test dressings. Treated The microbiological outcomes on P. aeruginosa and untreated wounds were harvested for sev- biofilm and the shedding planktonic cells in eral quantitative endpoints. Confirmatory studies response to different ofloxacin dosing regimens were performed to measure treatment impact on were not parallel and this may explain the in vitro P. aeruginosa and in vivo polybacterial non-coincidence of microbiological and clinical out- wounds containing P. aeruginosa and S. aureus. The comes with biofilm-associated infections. test dressing consistently decreased P. aeruginosa The current study introduced an unprecedented bacterial counts and improved wound healing com- novel dynamic model for the assessment of the pared to inactive vehicle and active control wounds microbiological outcome on both biofilm and shed- (p < 0.05). In vitro bacterial counts were also sig- ding planktonic cells of P. aeruginosa in response nificantly reduced following test dressing therapy to different dosing regimens of ofloxacin, which, in (p < 0.05). Similarly, improvements in bacterial bur- turn, can simulate the clinical outcomes in biofilm- den and wound healing were also achieved in associated infections of P. aeruginosa, e.g., cystic polybacterial wounds (p < 0.05). This study rep- fibrosis. Different scenarios of antibiotic dosing resented the first quantifiable and consistent regimens against biofilm-related infections can be in vivo evidence of a topical antimicrobial dress- mimicked using such a model. ing’s impact against established wound biofilm. Biofilms also occur in chronic rhinosinusitis The development of clinically applicable therapies (CRS), which is a highly prevalent disease in the against biofilm such as this is critical to improving adult and pediatric population; it causes a signifi- chronic wound care. cant burden and the management is considered one Bacteria survive in nature by forming biofilms of the most costly public health expenditures. on surfaces and probably most, if not all, bacte- Comorbidities include asthma, aspirin sensitivity, ria (and fungi) are capable of forming biofilms. and nasal polyposis. S. aureus biofilms and exotox- A biofilm is a structured consortium of bacteria ins that act as super-antigens have been implicated embedded in a self-produced polymer matrix con- to play an important pathological role in the inci- sisting of polysaccharide, protein and extracellular dence, maintenance, and ongoing burden of CRS. A DNA. Bacterial biofilms are resistant to antibi- better understanding of the interplay between bac- otics, disinfectant chemicals and to phagocytosis terial factors, host factors, and the environment and other components of the innate and adap- will facilitate better management of this disease. tive inflammatory defense system of the body. This literature review focused on these factors and It is known, for example, that the persistence of highlighted current research in this field. staphylococcal infections related to foreign bodies In recent years, the number of multidrug- is due to biofilm formation. Chronic P. aeruginosa resistant bacteria has increased rapidly and several lung infections in cystic fibrosis patients are caused epidemics were identified in different regions by biofilm-growing mucoid strains. Gradients of of the world. Faced with this situation that nutrients and oxygen exist from the top to the presents a major global public health concern, bottom of biofilms and the bacterial cells located Antibiotic resistance 373 in nutrient poor areas have decreased metabolic Virulence and S. aureus activity and increased doubling times. These more or less dormant cells are therefore responsible for S. aureus is an opportunistic pathogen and the some of the tolerance to antibiotics. Biofilm growth leading cause of a wide range of severe clinical is associated with an increased level of muta- infections. The range of diseases reflects the diver- tions. Bacteria in biofilms communicate by means of sity of virulence factors produced by this pathogen molecules, which activates certain genes responsi-. To establish an infection in the host, S. aureus ble for production of virulence factors and, to some expresses an inclusive set of virulence factors such extent, biofilm structure. This phenomenon as toxins, enzymes, adhesins, and other surface is called quorum sensing and depends upon the proteins that allow the pathogen to survive under concentration of the quorum-sensing molecules in extreme conditions and are essential for the bacte- a certain niche, which depends on the number ria’s ability to spread through tissues. Expression of the bacteria. Biofilms can be prevented by and secretion of this array of toxins and enzymes antibiotic prophylaxis or early aggressive antibi- are tightly controlled by a number of regulatory otic therapy and they can be treated by chronic systems. S. aureus is also notorious for its abil- suppressive antibiotic therapy. Promising strategies ity to resist the arsenal of currently available may include the use of compounds that can dissolve antibiotics and dissemination of various multidrug- the biofilm matrix and quorum-sensing inhibitors, resistant S. aureus clones limits therapeutic options which increases biofilm susceptibility to antibiotics for a S. aureus infection. The development of anti- and phagocytosis. virulence therapeutics that neutralize S. aureus Acinetobacter baumannii, a Gram-negative, toxins or block the pathways that regulate toxin opportunistic pathogen can form biofilm and production has shown potential in thwarting the increasing resistance to antibiotic agents presents bacteria’s acquisition of antibiotic resistance. In challenges for infection control. A better this review, these authors provided insights into the understanding of the influence of biofilm forma- regulation of S. aureus toxin production and poten- tion and antibiotic resistance on environmental tial anti-virulence strategies that target S. aureus persistence of A. baumannii in hospital settings toxins. is needed for more effective infection control Successful methicillin-resistant S. aureus (MRSA). These authors studied high biofilm forming, clones have evolved to adapt to healthcare and clinical, multidrug-resistant-(MDR)-positive strains. environments such as the community and in live- Environmental, MDR-positive, low biofilm forming stock. The authors reviewed recent studies on clone strains had a 2.7 times increase in risk of cell adaptation and the importance of genes acquired death due to desiccation compared with their during horizontal gene transfer to survival in spe- MDR-negative counterparts. MDR-negative, high cific environments. The review also discussed biofilm-forming environmental strains had a 60% the role of global regulators controlling virulence decrease in risk compared with their low biofilm- gene expression and resistance to antibiotics, such forming counterparts. The MDR-positive phenotype as the agr and vraRS systems. The authors stated was deleterious for environmental strains and the that understanding these processes in successful high biofilm phenotype was critical for survival. clones could reveal novel targets for therapeutic This study provided evidence of the trade-off agents, which are urgently required to reduce the between antibiotic resistance and desiccation infection burden and improve treatment options tolerance, driven by condition-dependent adap-. The effect of decolonization on the control tation, and establishes rationale for research of methicillin-resistant S. aureus (MRSA) may differ into the genetic basis of the variation in fit- depending on intensive care unit (ICU) settings and ness cost between clinical and environmental the prevalence of antiseptic resistance in MRSA. isolates. Community-associated methicillin-resistant S. In this study, an interdisciplinary team imple- aureus (CA-MRSA) is a prevalent cause of skin mented a screening program targeting patients with and soft tissue infections (SSTI), but the associa- a history of methicillin-resistant S. aureus (MRSA) tion between CA-MRSA colonization and infection to reduce unnecessary contact isolation. After remains uncertain. These authors studied the car- converting from a 2-step culture-based protocol to riage frequency at several body sites and the single polymerase chain reaction (PCR) testing, the diversity of S. aureus strains from patients with authors increased the efficiency of the screening and without SSTI. Specimens from the nares, program from 77% to 100%. Despite the higher cost throat, rectum, and groin of case subjects with of PCR-based testing, this program remained cost- a closed skin abscess (i.e., without drainage) and saving. matched control subjects without a skin infection 374 M. Frieri et al. presenting to 10 U.S. Emergency Departments were susceptibility testing methods for S. aureus, and cultured using broth enrichment; wound specimens should be readily adaptable to different antibiotics were cultured from abscess cases. Methicillin resis- and bacterial species as new mechanisms of resis- tance testing and spa typing were performed for tance or multidrug-resistant pathogens evolve and all S. aureus isolates. S. aureus was found in appear in clinical practice. 57.8% of abscesses; 49 isolates were MRSA, and 36 Healthcare workers may acquire methicillin- were methicillin-susceptible S. aureus (MSSA). resistant S. aureus (MRSA) from patients, both S. aureus-infected subjects were usually (75/85) hospital and home environments, other health- colonized with the infecting strain; among MRSA- care workers, family and public acquaintances, and infected subjects, colonization was most common pets. There is a consensus of case reports in the groin. The CC8 lineage accounted for most and series that now strongly support the role for of both infecting and colonizing isolates, although MRSA-carrying healthcare personnel to serve as a more than 16 distinct strains were identified. Nearly reservoir and as a vehicle of spread within health- all MRSA infections were inferred to be USA300. care settings. Carriage may occur at a number of There was more diversity among colonizing than body sites and for short, intermediate, and long infecting isolates and among those isolated from terms. A number of approaches have been taken to controls versus cases. Detection of S. aureus col- interrupt the linkage of staff-patient spread, but onization, and especially MRSA, may be enhanced most emphasis has been placed on handwashing by extranasal site culture. and the treatment of staff MRSA carriers. The This study was conducted in a 14-bed surgi- importance of healthcare workers in transmission cal ICU over a 40-month period. The baseline has been viewed with varying degrees of interest, period featured active surveillance for MRSA and and several logistical problems have arisen when the institution of contact precautions. MRSA decol- healthcare worker screening is brought to the fore- onization via chlorhexidine baths and intranasal front. There is now considerable support for the mupirocin was implemented during a subsequent screening and treatment of healthcare workers, 20-month intervention period. Both pre-post but it is suggested that the intensity of any such and interrupted time series analyses were used approach must consider available resources, the to evaluate changes in the clinical incidence of nature of the outbreak, and the strength of the hospital-acquired MRSA colonization or infection. epidemiological associations. The task of assessing MRSA isolates were tested for the presence of healthcare personnel carriage in any context should qacA/B genes and mupirocin resistance. be shaped with due regard to national and interna- In pre—post analysis, the clinical incidence tional guidelines, should be honed and practiced of MRSA significantly decreased by 61.6% after according to local needs and experience, and must implementation of decolonization (p < 0.001). be patient-oriented. Interrupted time series analysis showed decreases S. aureus is an important human pathogen, in both the level and trend of clinical MRSA responsible for infections in the community incidence. Of 169 MRSA isolates, 64 carried the and healthcare settings. Although much of the qacA/B genes, and 22 showed a high level of attention is focused on the methicillin-resistant resistance to mupirocin. Low-level mupirocin resis- ‘‘variant’’ MRSA, its methicillin-susceptible coun- tance significantly increased from 0—19.4% during terpart (MSSA) remains a prime species in infections the study period. These authors felt that although. S. aureus epidemiology, especially that of decolonization using antiseptic agents was help- MRSA, has evolved rapidly in recent years. First rep- ful in decreasing hospital-acquired MRSA rates, the resenting a typical nosocomial multidrug-resistant emergence of antiseptic resistance should be mon- pathogen, MRSA has recently emerged in the com- itored. munity and among farmed animals due to its Current approaches to antibiotic susceptibil- ability to evolve and adapt to different settings. ity testing of cultured pathogens have several Global surveillance has shown that MRSA repre- limitations ranging from long run times to depend- sents a problem in all continents and countries, ence on prior knowledge of genetic mechanisms with an increase in mortality and the need for of resistance. These authors developed a rapid expensive last-resource antibiotics. S. aureus can antimicrobial susceptibility assay for S. aureus easily acquire resistance to antibiotics and MRSA is based on bacterial cytological profiling, which uses characteristically multidrug resistant. Newer quantitative fluorescence microscopy to measure anti-staphylococcal drugs have been developed, antibiotic-induced changes in cellular architecture but because their clinical use has been very limited. Thus, bacterial cytological profiling provides so far, little is known about the emergence of resis- a rapid and flexible alternative to gene-based tance. Molecular typing techniques have allowed Antibiotic resistance 375 identification of the major successful clones and validated by retrospective analysis of all cases lineages of MSSA and MRSA, including high-risk occurring in critically ill patients during 2013. The clones, and tracing their diffusion. In this tool was used to screen all patients admitted to earlier review, the authors depicted the most com- an intensive care unit. Evidence-based interven- mon clones circulating in different geographical tions were implemented for patients identified areas and in different present settings. The authors as being at high risk for health care-acquired stated that because the evolution of S. aureus will Clostridium difficile infection. Effectiveness continue, it is important to maintain the attention of the model was measured by the reduction on the epidemiology of S. aureus in the future with in the health care-acquired Clostridium difficile a global view. infection rate during the intervention period com- pared with the pre-intervention period. During Emergency Department the 12-month intervention period, 217 high- risk patients were identified as infected with Hand hygiene is essential in preventing nosoco- Clostridium difficile. Sixty-two of these met the mial infections. The Emergency Department is an exclusion criteria, resulting in a study popula- open portal of entry for pathogens into the hospital tion of 157 patients. During the pre-intervention system, hence the important sentinel function of phase, 10 cases occurred. During the 12-month Emergency Department personnel. The main study period, 2 cases were identified; the reduc- objective of this study was to assess the effect tion was statistically significant. Thus a strategy of a multimodal improvement strategy on hand for identifying patients at increased risk and the hygiene compliance in the Emergency Department implementation of multidisciplinary risk-mitigation. This was a prospective before-and-after study strategies is effective in reducing the incidence to determine the effect of a multimodal improve- of health care-acquired Clostridium difficile infec- ment strategy on the compliance of hand hygiene tion. in the Emergency Department according to the ‘‘My Residents of long-term care facilities are at 5 Moments’’ of hand hygiene defined by the WHO increased risk for colonization and development Interventions as education, reminders, and regu- of infections with multidrug-resistant organisms. lar feedback on hand hygiene performance and This study was undertaken to determine the role models were planned during the 3 intervention prevalence of asymptomatic rectal colonization weeks. A total of 57 Emergency Department with Clostridium difficile (and proportion of nurses and Emergency Department physicians were 027/NAP1/BI ribotype) or carbapenem-resistant observed in this study; approximately 1000 oppor- Enterobacteriaceae in the long-term care facilities tunities for handrubs were evaluated during the population. 3 intervention periods. Hand hygiene compliance Active surveillance was performed for C. diffi- increased significantly from baseline from 18% to cile and carbapenem-resistant Enterobacteriaceae 41% after the first intervention and stabilized to 50% rectal colonization of 301 residents in a 320-bed and 46% after the second and third interventions, (80-bed ventilator unit), hospital-affiliated long- respectively. Thus, implementing a multimodal term care facility with retrospective chart review hand hygiene improvement program significantly for patient demographics and potential risk factors improved the compliance of Emergency Depart-. Over 40% of patients had airway ventilation ment personnel. and received enteral feeding. One-third of these patients had prior C. difficile-associated infection. Clostridium difficile infection Asymptomatic rectal colonization with C. difficile occurred in 58 patients (19.3%, one-half with Health care-acquired Clostridium difficile infec- NAP1+), carbapenem-resistant Enterobacteriaceae tion is associated with adverse outcomes at both occurred in 57 patients (18.9%), and both occurred the organization and patient levels. Factors that in 17 patients. Recent carbapenem-resistant increase the risk for the development of health Enterobacteriaceae was significantly associated care-acquired Clostridium difficile infection have with an increased risk of C. difficile ± carbapenem- been identified. The objectives of this study resistant Enterobacteriaceae colonization. were to develop a predictive screening tool to Multivariate logistic regression analysis revealed identify patients at risk for health care-acquired the presence of tracheostomy collar to be sig- Clostridium difficile infection I and implement a nificant for C. difficile colonization, mechanical bundle of mitigation interventions. ventilation to be significant for carbapenem- A predictive screening tool was developed based resistant Enterobacteriaceae colonization, and on risk factors identified in the literature and prior Clostridium difficile infection to be significant 376 M. Frieri et al. for both C. difficile and carbapenem-resistant healthcare costs. Antibiotic usage, particularly of Enterobacteriaceae colonization. cephalosporins, has been associated with VRE col- Thus, the strong association of C. difficile onization and VRE bloodstream infections. These or carbapenem-resistant Enterobacteriaceae col- authors examined the relationship between antimi- onization with disruption of normal flora by crobial usage and incident VRE colonization at the mechanical ventilation, enteral feeds, and prior individual patient level. Prospective weekly Clostridium difficile infection carries important surveillance was undertaken for incident VRE col- implications for infection control intervention in onization was defined by negative admission but this population. positive surveillance swab in a medical intensive care unit over a 17-month period. Ninety- Vancomycin-resistant enterococci six percent of admitted patients were swabbed within 24 h of intensive care unit arrival; of the Between 2013 and 2014, a vancomycin-resistant 380 patients in the ICU long enough for weekly enterococci (VRE) outbreak occurred in a teaching surveillance, 22% developed incident VRE colo- hospital in France. The outbreak was possibly due to nization. Incident colonization was associated with the lack of implementation of recommended con- male gender, more previous hospital admissions, trol measures. The aim of this study was to identify longer previous hospital stay, and the use of the effect of the lack of adherence to control meas- cefepime/ceftazidime, fluconazole, azithromycin, ures for prevention of VRE acquisition in contact and metronidazole. After controlling for demo- patients taking into account individual risk factors graphic and clinical covariates, metronidazole was. Contact patients with VRE acquisition were the only antibiotic independently associated with compared to patients without VRE acquisition in incident VRE colonization. Their findings suggest terms of institutional characteristics and risk fac- that risk of incident VRE colonization differs tors. Between December 2013 and February 2014, between individual antibiotic agents and support 282 contact patients were included in the study. the possibility that antimicrobial stewardship may The prevalence of VRE acquisition was 6.4% and impact VRE colonization and infection. significant risk factors for VRE acquisition accord- These authors reported an outbreak of van- ing to logistic regression analysis included lack of comycin variable vanA+ enterococci (VVE) able isolation, hospitalization in the same hospital unit to escape phenotypic detection by current guide- as a VRE carrier patient and lack of isolation, hos- lines, and demonstrate the molecular mechanisms pitalization in a specific unit, age, hemodialysis, for in vivo switching into vancomycin resistance central venous catheter and surgery Antibiotic and horizontal spread of the vanA cluster. use was a significant risk factor for VRE acquisi- Forty-eight vanA+ Enterococcus faecium and one tion using univariate analysis. The findings of these Enterococcus faecalis isolates were analyzed for authors confirmed that the factors focused on by clonality with PFGE and their vanA gene cluster the study (lack of isolation and dedicated unit) had composition assessed by PCR and whole genome a significant effect on VRE acquisition as patient- sequencing of six isolates. The VVE had insertion associated factors. It highlighted the importance of of IS1542 between orf2 and vanR that attenuated observance of the guidelines. the expression of the vanHAX activator coded by Infections attributable to VRE have become vanRS. Growth of susceptible VVE occurred after increasingly prevalent over the past decade. 24—72 h of exposure to vancomycin due to exci- Prompt identification of colonized patients com- sion of the ISL3-family element. The vanA gene bined with effective multifaceted infection control cluster was located on a transferable broad host- practices can reduce transmission of VRE and aid range plasmid also detected in outbreak isolates in preventing hospital-acquired infections. The with different pulsotypes as well as one E. fae- clinical microbiology laboratory is being asked to calis. Horizontally transferable silenced vanA able support infection control efforts through early iden- to escape detection and revert into resistance dur- tification of potential patient or environmental ing vancomycin therapy represents a new challenge reservoirs. This review discussed the factors that in the clinic. Genotypic testing of invasive VSE by contribute to the increase in VRE as an impor- vanA-PCR is advised. tant healthcare-associated pathogen, the utility of laboratory screening and various infection control Control in the Emergency Department strategies and the available laboratory methods to identify VRE in clinical specimens. A prospective observational study was conducted at VRE infections are a public health threat a university-affiliated urban teaching hospital and associated with increased patient mortality and level-1 trauma and burn center. All adult patients Antibiotic resistance 377 who triggered a Code Sepsis in the Emergency being prescribed at increasing rates. There are Department between January 2010 and December significant demographic disparities in nationwide 2011 were included. Hospital mortality and antibiotic prescription practices. hospital loss of stay of sepsis are similar to those reported in other observational studies. This study confirmed a decline in the mortality of sepsis pre- Conclusion dicted by earlier longitudinal studies and should prompt a resurgence in epidemiological research of Antimicrobial resistance in bacterial pathogens is sepsis syndromes in the United States. a significant challenge that has a high morbid- How closely physicians follow Infectious Disease ity and mortality. Multidrug resistant patterns in Society of America guidelines is unknown, particu- Gram-positive and -negative bacteria are difficult larly in the Emergency Department observation unit to treat and may even be untreatable with con- where increasing numbers of patients are treated ventional antibiotics. Challenges associated with for these infections. The objectives of this paper bacterial infection and associated diseases are due were to describe (1) the antibiotic treatment pat- to the current shortage of effective therapies, terns in the Emergency Department observation lack of successful prevention measures, and lack unit; (2) physicians’ adherence to the Infectious of new antibiotics, which require development of Disease Society of America guidelines; and (3) fac- novel treatment options and alternative antimicro- tors that influence physicians’ prescribing practices bial therapies. Biofilms are involved in multidrug. This paper showed that physician antibiotic resistance and can present challenges for infection prescribing practices demonstrated poor adherence control. Virulence, S. aureus, Clostridium difficile to Infectious Disease Society of America guidelines infection vancomycin-resistant enterococci, and and were influenced by the patient’s age and sex. control in the Emergency Department were dis- Standardized antibiotic protocols for the treatment cussed. of skin and soft tissue infections to Infectious Dis- ease Society of America guidelines is unknown, particularly in the Emergency Department obser- vation unit, which would minimize physician Funding bias. The increase in antibiotic-resistant pathogens is No funding sources. believed to have influenced the Emergency Depart- ment epidemiology and management of infectious diseases since 2000. Competing interests Data from the National Hospital Ambulatory Med- ical Care Survey from 2000 to 2010 were used None declared. to examine temporal trends in the incidence of infectious diseases presenting to the Emergency Department. 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