cord-009967-fyqc5bat	2012	Recent studies have confirmed the efficacy and reduced expense of oral antibiotics prescribed for selected children with osteomyelitis and septic arthritis.1"22 In 1973, it was reported that favorable results ensued when oral antibiotic therapy was prescribed for hospitalized patients with serious infectionsz3 Fourteen patients with osteomyelitis were treated successfully with oral cephalexin after they had received a short course of parenteral cephaloridine. Adults with disseminated gonococcal infection can be effectively treated with a one week program consisting initially of 2 million units of penicillin G administered every 4 hours followed by oral ampicillin or amoxicillin prescribed as 500 mg four times daily.34,35 Hospitalization is usually recommended to establish the diagnosis of disseminated gonococcal disease since misdiagnosis occurs not infrequently with this disorder.33 Selected patients can complete the oral regimens in an outpatient setting or, alternatively, they can be treated entirely without ho~pitalization.~~ Acceptable oral regimens consist of giving amoxicillin (500 mg four times daily), tetracycline (500 mg four times daily), or erythromycin (500 mg four times daily) for at least 7 days.
cord-010012-1hrx1w8r	2012	The treatment of community‐acquired respiratory tract infections, such as acute exacerbations of chronic bronchitis (AECB), constitutes a huge socioeconomic burden. The treatment of community-acquired respiratory tract infections (RTIs), such as acute exacerbations of chronic bronchitis (AECB), constitutes a huge socioeconomic burden. Indeed, antibiotic treatment is associated with lower relapse rates, longer periods between exacerbations, shorter duration of symptoms, and reduced hospitalizations. However, studies of antibiotic therapy for AECB have failed to either account for differences among patients or examine the effect of increasing rates of antimicrobial resistance on clinical and economic outcomes. 22 It was concluded that this study found that in patients with COPD experiencing an AECB, the use of third-line antibiotics significantly reduced treatment failure rates and the need for hospitalization, while prolonging the time between AECB episodes. The infection-free interval: its use in evaluating antimicrobial treatment of acute exacerbation of chronic bronchitis
cord-010479-2zua4mji	2020	7 Correctly administered perioperative prophylactic antibiotics decrease the rate of SSIs. 1, 2 Clinical practice guidelines for antimicrobial prophylaxis published in the American Journal of Health-System Pharmacy recommend intraoperative antibiotic dosing intervals during surgical procedures based on the pharmacokinetics of each drug. The secondary project goal was to decrease SSIs. Methods: With recommendations from the Infectious Disease Society of America, we developed new organizational redosing guidelines, as well as a new antibiotic-specific reminder alert in the electronic medical record. The secondary project goal was to decrease SSIs. Methods: With recommendations from the Infectious Disease Society of America, we developed new organizational redosing guidelines, as well as a new antibiotic-specific reminder alert in the electronic medical record. Conclusions: This project demonstrates that comprehensive education along with antibiotic-specific electronic medical record alerts significantly increased the compliance of intraoperative antibiotic redosing at Children''s Hospital & Medical Center.
cord-011189-c0ytamge	2019	The real impact of MDRs on the outcomes of ICU patients is debatable, but despite this controversy, the incidence of MDRs is related to poor quality-of-care, as an expression of reduced compliance to hand hygiene [14] , and a high burden of antibiotic exposure [15] . De-escalation decreases the time of antibiotic use, but a short exposure still exists; in this way, a single antibiotic dose may be enough to treat severe infections such as Fig. 1 Two different mindsets in the decision making process to initiate antibiotics to critically ill patients who are getting worse. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensivecare-unit-acquired infection: a quasi-experimental, before and after observational cohort study
cord-011310-fm578rm5	2019	Several guidelines recommend the screen-and-treat strategy, i.e. active search for the presence of Helicobacter pylori infection and its eradication to prevent the possibility of gastric cancer. Furthermore, no differences in the eradication regimen are currently recommended, depending on whether the treatment is given for a clinically evident disease, e.g. for complicated ulcer disease or MALT lymphoma from prevention strategies in population-based settings. The recent guidelines of ASEAN (Association Southeast Asian Nations) countries support eradication to prevent gastric cancer by considering this strategy as costeffective, depending on the disease burden in the relevant community [19] . An expert group hosted by IARC has suggested the need for interventional strategies to decrease the burden of gastric cancer [1, 22] ; however, experts recommended that this be done by the means of well-designed clinical studies evaluating the feasibility, acceptance, costs, effectiveness and adverse consequences.
cord-013105-tmhce7p5	2020	In addition, we propose that health-care providers can bring concrete and direct benefits to each of our critically ill patients at the bedside by preventing the excessive use of unnecessary antibiotics. The clinical deterioration of mechanically ventilated patients may be associated with a new infection process; however, the majority of ventilator-associated events leading to antibiotic administration is related to noninfectious processes [6] ; thus, the appropriate antimicrobial de-escalation is essential and can be safely done if culture results are negative [7, 8] . For many decades, critically ill patients have been treated with antibiotics during two to three weeks for severe infections including pneumonias, abdominal and urinary infections, all of which still comprise the majority of infections leading to sepsis and admission to the intensive care unit. Effect of aminoglycoside and beta-lactam combination therapy versus beta-lactam monotherapy on the emergence of antimicrobial resistance: a meta-analysis of randomized, controlled trials
cord-016187-58rqc0cg	2006	Community and nosocomial outbreaks of multidrug resistant pathogens as evidenced by methicillin and vancomycin resistance [17] in Staphylococcus aureus and resistance to the new anti-viral neuraminidase inhibitors [18, 19] by recent infl uenza isolates are cause for real concern. Beta-lactam antibiotics have been known for almost 80 years and their widespread use has created selection pressures on bacterial pathogens to resist their inhibitory actions. These investigators discovered that the resistant strain had acquired a new methylase gene that blocked the binding site for inhibition by aminoglycosides on a specifi c sequence on 16S ribosomal RNA. Mutations resulting in the loss of specifi c porins can occur in clinical isolates and determine increased resistance to beta-lactam antibiotics. If we could discover new targets for future antimicrobial drugs it may be possible to keep pace or even exceed the rate of antibiotic resistance gene development by microbial pathogens.
cord-017393-kx8kmdej	2009	Despite numerous clinical studies, since the 1970s, no single empirical antibiotic regimen has been shown to be superior for initial treatment of patients who become febrile during a neutropenic episode after therapy with chemotherapy drugs for hematological malignancies (see Table 5 -2) [4, 9, [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] . Similarly, bacteremias due to Staphylococcus aureus, Pseudomonas aeruginosa, and Clostridium species as well as candidemias are more frequently encountered in patients with acute leukemia who suffer from neutropenic enterocolitis or typhlitis, the most serious disturbance of the delicate balance between mucosal damage and microbial flora in the setting of prolonged exposure to antibiotics after intermediate or high-dose cytarabine chemotherapy. In addition, if a persistently neutropenic patient has no complaints and displays no clinical, radiological, or laboratory evidence of infection, cessation of antibiotic therapy or a change to oral antimicrobials should be considered after 4 days without symptoms.
cord-017799-2nvrakbs	2018	Acute bacterial rhinosinusitis most commonly occurs as a complication of viral infection, complicating 0.5-2.0% of cases of the common cold [10] , However, other factors may also predispose to ABRS, such as allergy, immune dysfunction, impaired ciliary function, anatomic narrowing of the sinuses, or poor dentition [11] . Only for suspected complication involving orbit or central nervous system Similar recommendations for adults Initial therapy of ABRS Antibiotics for worsening course or severe onset ("2" or "3" above), but antibiotics or watchful waiting (for up to 3 days) for "persistent illness" ("1" above) 
cord-018557-iuu38yes	2009	Treatment recommendations from the AAP/AAFP guidelines for the management of acute otitis media suggest that observation rather the initial use of antibiotics is appropriate depending on the child''s overall health, age, severity of illness, and likelihood that they can follow-up if necessary. When antibiotics are selected for the management of acute suppurative otitis media, selection of an agent should provide coverage for the two most common organisms, the AAP/AAFP recommends initial treatment with amoxicillin at a dose of 80-90 mg/kg per day. • Evidence does not support the use of antibiotics for the common cold, acute bronchitis, initial cases of otitis media with effusion, and non-group A streptococcal pharyngitis. • Although the data are mixed regarding the utility of antibiotic treatment for acute sinusitis, otitis media, and group A streptococcal pharyngitis, antibiotics may have some benefit.
cord-018566-dd5gw66t	2018	This chapter examines the evidence for antibiotic resistance in the United States and globally, the public health implications, and the impact of—and related industry and political responses to—antibiotic use in animal feed. The major stakeholders include pharmaceutical companies, production integrators, feed suppliers, farm groups, producers, restaurants, food retailers, the public, the medical community, the scientific community, government regulators and policy makers. In 1969, the United Kingdom''s (UK) Parliament received the Swann Report, which concluded that using antimicrobials at sub-therapeutic levels in food-producing animals created risks to human and animal health (Joint Committee on the use of Antibiotics in Animal Husbandry and Veterinary Medicine 1969). This scenario could be exacerbated to the extent FSIS approves additional international facilities, local regulations, and inspections as "equivalent to the United States." Future trade agreements will need to include provisions which address reduced use of medically important antibiotics in producing food animals.
cord-021158-075vh5jg	2020	Using recent debates on the AMR problem, it proposes to examine the relationship between the development of professional veterinary expertise and of the drug market, based on the case of a specific segment of the profession, namely veterinarians specializing in industrial poultry and pig production in western France. Indeed, it is common to hear professional organizations or public authorities state that in order to reduce their economic dependence on antibiotic sales, vets must rethink their activity by favouring preventive approaches to animal health which would involve a diversified range of services and would contribute to placing vets in an advisory role with a holistic vision of livestock farming or even of the food supply chain (VetFuturs France 2018) .
cord-021419-nypnib0h	2020	In this review, the following classes of compounds are considered as scaffolds for the synthesis of new antibiotics: polycyclic glycopeptides of the vancomycin ± teicoplanin group, classical macrolides, macrolides of the amphotericin B ± oligomycin group, anthracyclines, aureolic acid derivatives, heliomycin, synthetic benzoxaboroles and some other antibiotics. 42 Antibacterial activity of derivatives 52 ± 55 modified at the C(11)7OH group of the aglycone was evaluated compared to the starting antibiotics vancomycin (1) and azithromycin (30) on a panel of Gram-positive and Gramnegative bacterial strains (8 and 3 strains, respectively). In order to improve antifungal properties, cytotoxic and therapeutic characteristics and to study the mechanisms of action, series of new semi-synthetic derivatives based on AmB (63a) and bioengineered analogues S44HP (64a), BSG005 (65a), BSG022 (66a), BSG019 (67), BSG003 (68a) and BSG018 (69) were synthesized (in collaboration with the company BIOSERGEN, Norway) (Scheme 17).
cord-027860-s97hdhh6	2020	Although common upper respiratory bacterial pathogens, such as Moraxella (Branhamella) catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, may be isolated from patients with acute bronchitis, their relevance is questionable because these bacteria can be present in the respiratory tract of healthy individuals. In the treatment of Bordetella pertussis, early administration of a macrolide antibiotic and patient isolation will likely decrease coughing paroxysms and limit spread of disease (Braman, 2006) (SOR: A). Risk factors for Pseudomonas infection include severe structural lung disease (e.g., bronchiectasis) and recent antibiotic therapy, health care-associated exposures or stay in hospital (especially in the ICU). Patients who present with severe infection or whose infection is progressing despite empiric antibiotic therapy should be treated more aggressively; the treatment strategy should be based on results of appropriate Gram stain, culture, and drug susceptibility analysis. For suspected MRSA skin infections, oral treatment options include trimethoprim-sulfamethoxazole, clindamycin, and doxycycline of purulent material when performing incision and drainage in the event that the patient fails to improve and antibiotic coverage becomes necessary.
cord-030184-5iv6qt7t	2020	Fecal microbiota transplant has been found to be one of the most effective ways to regulate the gut microbiota dysbiosis in the setting of CDI [49] Fecal microbiota transplant has been studied in gut decolonization of MDRO, but has not conclusively been found to be effective [55, 56, 58] Selective oral decontamination and selective digestive decontamination with oral antibiotics has been evaluated as a means of reducing infections caused by endogenous MDRO, but has not been found to be efficacious [61] [62] [63] Restoration of the gut microbiota diversity through probiotics and prebiotics have some role in restoring gut diversity in specific diseases, such as necrotizing enterocolitis, acute infectious diarrhea and antibiotic-associated diarrhea [64] [65] [66] [67] [68] [69] Randomized controlled trials have shown positive effects on gut health by probiotics in a myriad of conditions, such as infectious and antibiotic-associated diarrhea (AAD), irritable bowel syndrome, and enterocolitis [64] .
cord-252243-ua2w6xki	2020	Results: Staff were very aware of common UTI symptoms and nitrofurantoin as first-line treatment, but some were less aware about when to send a urine culture, second-line and non-antibiotic management, and did not probe for signs and symptoms to specifically exclude vaginal causes or pyelonephritis before prescribing. • Clearly outlines how to clinically assess someone with suspected UTI; • Includes prompts/considerations around differential diagnosis, pyelonephritis, and sepsis; • Clearly outlines the steps for clinical assessment of someone with suspected UTI and when a urine dipstick test or culture is needed; • Provides information on the sensitivity and specificity when using urine dipsticks to diagnose a UTI for women under 65 years; • Has been developed as an update to previous guidance; • Links to latest national guidance on antimicrobial prescribing for UTI management (developed since this study was conducted); • Links to UTI leaflets and resources for women under 65 years that explains evidenced-based prevention and self-care recommendations.
cord-255635-0pr9oae6	2020	on the antiseptic efficacy of povidone-iodine (PVP-I) against SARS-CoV-2; we aim to demonstrate the potential prophylactic capacity of the new generation of uncomplexed molecular iodine (I 2 ) mouthwashes. The number of antibiotics dispensed each month by community pharmacists in England relating to NHS dental prescription forms from January 2018 to May 2020 is given in Figure 1 . 2 Antibiotics may have been used: • As a ''quick fix'' to avoid the life-time impact of an unnecessary extraction, in anticipation that AGPs might soon be permissible in general dental practices • Because dentists felt pressured by some patients for antibiotics, irrespective of their efficacy or appropriateness for treating toothache • Because of difficulties diagnosing a patient''s condition remotely prompting a ''just in case'' approach through concerns of life-threatening deterioration without treatment • As some UDCs were requiring patients to have tried antibiotics before accepting referral for face-to-face care, highlighting system and process impact on antibiotic prescribing.
cord-257244-gryp0khc	2017	Despite these important associations, the use of antiinfectives (antibiotics, antivirals, antifungals, vaccines) that specifically target known pathogens, or drugs that are based on or exploit microbe-host receptor interactions (toll-like receptor agonists, bacterial lysates) or are immunomodulators (vitamin D), and/or may work in part by altering our associated microbiology (probiotics) are, with the exception of severe asthma, seldom considered in asthma treatment, prevention and guidelines. Overall, antibiotic use is associated with asthma risk rather than protection at most stages of human development, including pregnancy, 10, 11 early life 12 and childhood, 13 although why this is so is a subject widely debated. 10 In retrospective studies, the association between antibiotic use and increased risk of asthma or wheezing in children is further confused due to the potential of reverse causation. Inhibiting virus replication through interfering with viral enzymes active within cells poses additional problems in drug discovery; however, several useful inhibitors for respiratory tract viruses have found their way into phase I/II clinical trials.
cord-257460-e6anaxck	2007	As such, the term URI has come to encompass multiple clinical entities including pharyngitis, sinusitis, and bronchitis, as well as nonspecific respiratory infections, a designation that includes the common cold. Use of a sore throat score to determine treatment of children and adults in a university-based family practice demonstrated a 48% reduction in antibiotic prescription compared with usual care [35] . Acute bacterial rhinosinusitis (ABRS) shares symptoms with the viral URI, including rhinorrhea, nasal congestion, facial pressure, and fever, which may lead the patient to request antibiotics from their physician. Like pharyngitis and sinusitis, however, it is a condition that shares a primary symptom, in this case cough, with the nonspecific URI, an illness of viral origin not requiring antibiotic therapy. A Patient education by the physician on the appropriate treatment of acute bronchitis can result in lower antibiotic usage without affecting clinical outcomes [93] . Principles of appropriate antibiotic use for treatment of nonspecific upper respiratory tract infections in adults
cord-259945-nmjwzk4e	1999	Only randomized trials that enrolled otherwise healthy patients with a diagnosis of acute bronchitis, used an antibiotic in the treatment group and a placebo in the control group, and provided sufficient data to calculate an effect size were included. Only randomized trials that enrolled otherwise healthy patients with a diagnosis of acute bronchitis, used an antibiotic in the treatment group and a placebo in the control group, and provided sufficient data to calculate an effect size were included. Inclusion criteria consisted of the following: randomized trials using an antibiotic in the treatment group and a placebo in the control group; subjects with acute bronchitis, no history of chronic lung disease, and pneumonia excluded by chest radiograph or clinical exam; therapy for at least 5 days; and the presentation of sufficient data to calculate the difference in efficacy between the treatment and the placebo as a continuous variable.
cord-263430-zq6huaoz	2020	title: The Primary Care Perspective on the Norwegian National Strategy against Antimicrobial Resistance Hence, a substantial proportion of antibiotic prescriptions are issued by primary care physicians, implying that this part of the healthcare sector needs to be heavily involved in any strategy to reduce AMR. Three of the specific goals for the healthcare sector in the current strategy are directly relevant for primary healthcare (Box 2), including reducing antibiotics use by 30%, reducing the number of prescriptions from 450 to 250 per 1000 inhabitants, and reducing prescriptions for respiratory infections by 20%-all compared to the 2012 level. Both primary care physicians and the general population may question the safety and legitimacy of "ever lower antibiotic prescription" and thus jeopardize the strong alliance between healthcare providers, public health authorities and the population, which has been a key success factor in the present strategy.
cord-267023-w5ig7mrl	2017	We integrated case-based modules, group learning activities, smartphone applications (apps), decision support tools, and prescription audit and feedback into curricula of the medical school, medicine residency program, infectious diseases (ID) fellowship program, and hospital medicine program operations. In a 2013 follow-up multicenter survey of fourth year medical students, 90% desired further education on antimicrobial prescribing, but only 40% were familiar with the role of antimicrobial stewardship (AS) in promoting judicious antimicrobial use and preventing multidrug resistance [3, 4] . It consists of 5 educational strategies designed to bridge perceived learning gaps and lay the foundation for best practices in stewardship and infection prevention in medical students, postgraduate trainees, and mature clinicians. The majority used a quasi-experimental, before-and-after study design with preand postintervention knowledge assessment questions, surveys of learners, or chart review with post-antibiotic prescription audit as methods of evaluation.
cord-270051-rs3cz9lq	2020	The number of antibiotics dispensed each month by community pharmacists in England relating to NHS dental prescription forms from January 2018 to May 2020 is given in Figure 1 . This is despite the significantly poorer access to dentistry (only around 7,500 patients were seen at designated urgent dental centres [UDCs] across England) compared to May when the capacity of these centres increased and saw over 27,000 patients. 2 Antibiotics may have been used: • As a ''quick fix'' to avoid the life-time impact of an unnecessary extraction, in anticipation that AGPs might soon be permissible in general dental practices • Because dentists felt pressured by some patients for antibiotics, irrespective of their efficacy or appropriateness for treating toothache • Because of difficulties diagnosing a patient''s condition remotely prompting a ''just in case'' approach through concerns of life-threatening deterioration without treatment Finally, the NHS may have seen an influx in patients who might otherwise receive care privately, resulting in an increase in NHS dental prescriptions as, anecdotally, not all practices were open for telephone triage during April and May 2020.
cord-275700-tx4hirm4	2002	Because of the increasing bacterial resistance to antibiotics, the cost of prescription drugs, and the potential adverse reactions to them, the present management of acute bronchitis has important shortcomings. This definition highlights the first two steps for treatment: 1) identify patients who have chronic pulmonary disease or other coexisting medical illnesses such as congestive heart failure or immunosuppression and 2) appropriately rule out other causes of acute cough, such as pneumonia and sinusitis. For the patient who presents with acute onset of cough and no history of chronic pulmonary disease or evidence of other more serious illnesses, studies have consistently shown either no benefit or, at best, modest benefit from the use of antibiotics. Antibiotic prescribing for adults with colds, upper respiratory tract infections and bronchitis by ambulatory care physicians National trends in the use of antibiotics by primary care physicians for adult patients with cough
cord-279483-gwikyux2	2020	title: Risk prediction models to guide antibiotic prescribing: a study on adult patients with uncomplicated upper respiratory tract infections in an emergency department We aim to provide an evidence-based clinical decision support tool for antibiotic prescribing using prediction models developed from local data. From 2009 to 2010, adults had the highest rate of inappropriate antibiotic use for acute respiratory tract infections (URTIs, influenza, and viral pneumonia), with 500 antibiotic prescriptions per 1000 ED visits for adults aged 20-64 years and 666 per 1000 visits for those aged > = 65 years [10] . In this study, we aim to develop prediction models based on local clinical and laboratory data to guide antibiotic prescribing for adult patients with uncomplicated URTI with the ultimate goal of deploying them as an evidencebased clinical decision support tool for routine practice. Antibiotic prescribing for patients with upper respiratory tract infections by emergency physicians in a Singapore tertiary hospital
cord-280158-3fhhuzg5	2020	The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. The pharmaceutical industry abandoned NP divisions long ago in favor of high throughput screens of compound libraries against novel drug targets (another failure, see below); or, more productively to create next generation derivatives of existing antibiotics, a strategy that has worked well and continues today as judged by the number of analogues in the current pipeline.
cord-281188-0cql96hu	2020	(1) only free drug is active against the target bacteria, and protein binding of the drug decreases the rate of killing 19 ; (2) there are structures (such as porins) and mechanisms facilitating drug uptake, but also barriers that prevent the drug from entering the cells 20 ; (3) the drug can be pumped out, so the concentration needed for killing takes longer to achieve 21, 22 ; (4) the antibiotics with weak target-binding affinity will take longer to achieve the doses necessary for killing than those with greater affinity 23 ; (5) the targeted function might increase in the presence of the drug, thereby compensating for the inhibition by the drug 24 ; (6) the target function corresponds to the build-up of a cellular structure with slow turnover, which increases the amount of time for the antibiotic to kill 25,26 ; (7) the cells repair the damage produced by the antibiotics at rates that differ between drugs 27 ; (8) the damaged bacteria have inducible antibiotic-deactivating mechanisms 28 ; (9) the bacteria use alternative metabolic pathways that, to some extent, bypass those inhibited by the antibiotic 29, 30 ; (10) antibiotics differ in the extent to which they induce reactive oxygen species (ROS; deleterious) or SOS (potentially protective) responses and thereby the rate at which they kill the exposed bacteria [31] [32] [33] [34] ; (11) members of the antibiotic-exposed populations are either www.nature.com/nrmicro not replicating or are replicating slowly, and as such are killed at lower rates than the more active members of the population or their death is delayed; (12) the antibiotics produce a kind of ''stationary phase'' by activating the general RpoS-mediated stringent response 35 .
cord-281836-j1r771nq	2020	Global Health is based on a broad collaborative and transnational approach to establish "health for all humans." In this case, it focuses AR at a general (global) scale, considering that the selection and global spread of antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs) are a problem that influences the health of human societies with disparate social and economic structures and is linked to many societal and ecological factors (Chokshi et al., 2019) . Although not belonging to the antibiotic resistome, genes frequently associated with resistance to other antimicrobials, such as heavy metals or biocides, as well as the genes of the MGEs backbones, eventually involved in the transmission and selection of ARGs among microbial populations, the mobilome at large, are also relevant to track the emergence and dissemination of AR among different habitats Martinez et al., 2017; Baquero et al., 2019) .
cord-282628-6uoberfu	2020	The causative agent of most emerging infectious diseases is viruses; every year approximately more than two novel viral pathogens are identified, which can cause illness in a human. Factors for emergence include natural process (evolution of pathogen), infectious agents transfer from vertebrate to mammals, antimicrobial resistance (AMR), and climate change. The factors responsible for the emergence of infectious diseases such as (1) the evolution of new strain, (2) the introduction of a host to enzootic, (3) translocation of infected wildlife, (4) farming practices, and (5) others were provided. Due to emergence of antibiotic-resistant pathogens and unavoidable use of antibiotics, concomitant environmental perturbation caused by climate change might make the earth is not suitable for humans and other livings. Increasing resistance to antibiotics and the emergence of "superbugs" that are resistant to drugs of last resort have highlighted the great need for alternative treatments of bacterial disease. Furthermore, development of drug-resistant organisms and increased pathogen survival rate, only raising panic about the human, animal, and environmental health.
cord-286574-t9z2ynt5	2017	Data on the economic impact of AMR in major pathogens showed that healthcare costs significantly increase in the treatment of infections caused by antibiotic-resistant strains (Maragakis et al. In principle, the major high-level goals consist of optimizing the use of such drugs in health and agriculture and minimizing environmental contamination; sustaining the development of new classes of antimicrobials drugs and other medicines and making them affordable and accessible to all who need them; and much more effective application of infection control and prevention principles. These new agents are bound to change the paradigm for the treatment of infections caused by colistin-resistant Gram-negatives, but uncertainties are still likely to remain, including which agent to use, how to optimize dosing in to maximize efficacy and minimize toxicity as well as potential for development of resistance, and whether use of more than one agent would still be needed.
cord-289382-bnl9i9oy	2010	• the spread of virulent MRSA (methicillin-resistant Staphylococcus aureus) in the community; • the rise of multi-drug resistant Neisseria gonorrhoea; • the emergence and global dissemination of multi-drug resistant Acinetobacter baumannii, Pseudomonas aerugi nosa, Klebsiella pneumoniae and Enterobacteriaceae; • the spread of extensively drug resistant Mycobacterium tuberculosis; • the development of resistance to the two newest antibiotics to be approved for clinical use -daptomycin and linezolid. Microbial natural products have evolved over millennia to interact with biological molecules, whereas the synthetic chemical libraries used in antibiotic drug-discovery screens were generally developed with a focus on eukaryotic drug-discovery campaigns, as noted earlier. Efforts to develop physical-property rules for antibiotics and to incorporate natural-product-like chemical complexity in libraries of synthetic chemicals will no doubt improve success in identifying new synthetic antibiotic leads. Furthermore, natural-product producing bacteria from non-soil environments are being investigated and these have already resulted in new chemical matter, suggesting that there is a fantastic wealth of untapped chemical diversity waiting to be discovered.
cord-292094-vmsdhccp	2007	Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be candidates for outpatient treatment. A respiratory fluoroquinolone should be used for penicillin-allergic patients.) Increasing resistance rates have suggested that empirical therapy with a macrolide alone can be used only for the treat-ment of carefully selected hospitalized patients with nonsevere disease and without risk factors for infection with drug-resistant pathogens. Advantages include the high specificity, the ability of some assays to distinguish between influenza A and B, the rapidity with which the results can be obtained, the possibly reduced use of antibacterial agents, and the utility of establishing this diagnosis for epidemiologic purposes, especially in hospitalized patients who may require infection control precautions.
cord-295605-c6z9n3ij	2009	OBJECTIVE: We explored the prescribing patterns of physicians in North Trinidad in treating upper respiratory tract infections (URTI) in paediatric patients and the appropriateness of drugs prescribed. CONCLUSIONS: A large proportion of paediatric patients diagnosed with an URTI in North Trinidad was prescribed antibiotics although not indicated The inappropriate use of antibiotics can potentiate the worldwide trend of antimicrobial resistance. 8 Data from the National Centre for Health Statistics in the United States indicate that in recent years, approximately 75% of all outpatient prescriptions for antimicrobial medications have been issued primarily for five conditions: otitis media, sinusitis, bronchitis, pharyngitis or non-specific URTIs. 9 The majority of URTIs are of viral origin, due to rhinovirus, parainfluenza virus, coronavirus, adenovirus, Coxsackie virus, and influenza virus. 15 Mohan et al in 2004 reported that the five most frequent URTIs presenting in children in Trinidad are the common cold, pharyngitis, tonsillitis, sinusitis and acute otitis media in rank order.
cord-297125-la20vi9j	2016	In just the past year, the United States has been bombarded with headlines on the dangers of infectious diseases: "HIV ''Epidemic'' Triggered by Needle-Sharing Hits Scott County, Indiana [1] ;" "American with Ebola Now in Critical Condition [2] ;" "Seasonal Flu Vaccine Even Less Effective than Thought: CDC [3] ;" "''Superbug'' Outbreak at California Hospital, more than 160 Exposed [4] ;" "Deadly CRE Bugs Linked to Hard to Clean Medical Scopes [5] ;" "Painful Virus [Chikungunya] Sweeps Central America, Gains a Toehold in U.S. Many factors have reduced the number of new antibiotics approved in the United States each year as well as reduced domestic production including demanding Food and Drug Administration (FDA) regulations, the cost and time to market of development, the consolidation in the pharmaceutical industry, and the lack of financial impetus to produce and distribute antibiotics, which are generally used on a one-off basis versus drugs used to treat chronic conditions such as statins, Viagra, and allergy medications.
cord-297216-1b99hm1e	2020	In the Anthropocene, the conditions for microbial evolution have been altered by human interventions, and public health initiatives must recognize both the beneficial (indeed, necessary) interactions of microbes with their hosts as well as their pathogenic interactions. Its website proclaims this to be a big genome, big data approach to public health, whereby "taking into account individual differences in lifestyle, environment, and biology, researchers will uncover paths toward delivering precision medicine..." PPH is getting a shot in the other arm from pharmacogenomics, the study of how responses to drugs are influenced by the genetic makeup of the person receiving the drug. Holobiont public health would do well to recognize both the parasitic and the mutualistic branches of symbiosis [204] It would also recognize the two major changes in our scientific knowledge of microbial evolution that have occurred in this century: (1) organisms are holobionts composed of several species, wherein microbes help maintain healthy physiology and resilience; and (2) bacteria can pass genes through horizontal genetic transmission, thereby facilitating the rapid spread of antibiotic resistance through numerous bacterial species.
cord-304972-aktfbriw	2015	4---7 In normal practice, a diagnosis is made based on clinical criteria (fever, tonsillar exudate, anterior cervical lymphadenopathy and no cough), which are of low sensitivity in predicting GABHS (49%---74%), and therefore the indication for the prescription of antibiotics increases as there are a great many false positives. Validity depends on the sample collection technique (false-negative results can be given when little material has been obtained), on the area from which it is collected (there is a better yield when collected from the tonsils and/or the wall posterior to the pharynx), on the culture procedure and conditions, on the probability of streptococcal infection (some authors have found a spectrum bias, so that the sensitivity of Strep A increases the higher the Centor criteria number presented by a patient), the presence of other germs in the pharynx (false-positive results can be given if the pharynx presents major growth of Staphylococcus aureus), on the use of tests which are past their expiry date, and on commercial brand.
cord-306600-cxz8hf9q	2019	Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. pneumoniae lung infection, we recently demonstrated that combination treatment with mucosally administered flagellin and an orally or intraperitoneally administered low-dose (i.e., subtherapeutic) antibiotic is more effective than the antibiotic alone (i.e., with a lower bacterial load in the lung, and a lower mortality rate). Our data showed that several antimicrobial peptides (S100A9), cytokines (IL-1β and TNF), and chemokines (CCL20, CXCL1, and CXCL2) that were associated to epithelial responses are also upregulated after the administration of the combination treatment in the post-flu superinfection model, suggesting that the epithelium is also an important flagellin-specific driving force in the lung damaged by viral and bacterial infections.
cord-307429-ll109j3i	2017	The authors conducted a comprehensive literature review to explore the antibiotic resistance profile of bacteria associated with pneumonia in the Western Pacific Region, with a focus on Vietnam. In order to encourage more rational use of intravenous antibiotics in children with communityacquired pneumonia, the authors performed a comprehensive review of common bacterial pathogens and their reported drug resistance profiles in the Western Pacific Region-Vietnam in particular. PubMed, Google Scholar and Embase databases were searched using the following terms: antibacterial agents OR antibiotics OR drug therapy AND community acquired pneumonia OR acute respiratory tract infection AND child OR children OR childhood. With enhanced diagnostic tools, respiratory viruses and atypical bacteria such as Mycoplasma pneumonia are commonly detected in children with community-acquired pneumonia, particularly in studies from the Western Pacific Region [7] [8] [9] . Despite the available evidence, most doctors in Vietnam routinely hospitalize children with "clinical pneumonia" to administer intravenous antibiotics; unnecessary hospitalization increases both healthcare cost and the risk of nosocomial infection.
cord-308001-gkd9d3k0	2020	In a 1999 survey of GPs, we found that genital chlamydia infection, antibiotic resistance surveillance, vaginal discharge, leg ulcers, sinusitis, otitis media/externa, dyspepsia/Helicobacter pylori, Creutzfeldt-Jakob disease (CJD) and tonsillitis were the top 10 priorities for improvements to diagnostic tests, and stronger evidence on which to base treatment decisions [9, 10] . Of the 27 named conditions/illnesses, suspected infection in the elderly (82.2%), recurrent urinary tract infection (UTI) (81.2%), surveillance of antibiotic resistance in the community (81.0%), leg ulcers (75.4%), and persistent cough (75.2%) were the five most highly rated illness/conditions where respondents felt they required more evidence to support their daily practice. Of the 27 named conditions/illnesses, suspected infection in the elderly (82.2%), recurrent urinary tract infection (UTI) (81.2%), surveillance of antibiotic resistance in the community (81.0%), leg ulcers (75.4%), and persistent cough (75.2%) were the five most highly rated illness/conditions where respondents felt they required more evidence to support their daily practice.
cord-308480-t2vukbwp	2011	In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. Taking two typical antibiotics, imipenem and carbapenem as example, the docked complex structures revealed that although the antibiotics adopted diverse conformations in the active site, the lactam motifs were positioned in the same orientation by coordinating with zinc ions tightly ( Figure 2C ), which suggested that the catalytic mechanisms were highly conserved among B1 subclass enzymes, as shown in Figure 3 . To gain the structural insight into the mechanism of the potent hydrolysis of NDM-1, the intermolecular interactions of three models of NDM-1, VIM-2 and FEZ-1 in complex with antibiotics meropenem were compared and analyzed in details ( Figure 4A -C).
cord-310474-hip7t0jx	2020	Although the future potential of nontraditional therapies is viewed with cautious optimism, adequate resourcing will be critical to demonstrate clinical impact, especially when many of the translational criteria associated with direct-acting small molecule therapeutics will likely be incongruent with the nontraditional development pathway. The three review articles by Zurawski and McLendon [5] , Nikolich and Filippov [6] , and Ghose and Euler [7] give a superb timely survey of how monoclonal antibodies, bacteriophages and lysins, respectively, are currently being explored in the treatment of bacterial infections. Turning to small molecule therapeutics, Frei''s perspective on the untapped potential of metal complexes as antibiotics provides a compelling view that chemical classes often misconstrued as only being useful for certain applications should not be overlooked as potential sources of new chemotypes to fight bacterial infections [8] . Critical Parameters for the Development of Novel Therapies for Severe and Resistant Infections-A Case Study on CAL02, a Non-Traditional Broad-Spectrum Anti-Virulence Drug
cord-312266-hnbgaxft	2016	The Haemophilus influenzae type b (Hib) vaccine and the pneumococcal conjugate vaccines are increasingly available in both developed as well as developing countries, especially the 7-and 13-valent pneumococcal conjugate vaccines which have shown effectiveness in reducing the incidence and severity of pneumonia and other lower respiratory infections in children. 61 The efficacy of ribavirin for the treatment of RSV CAP in infants is debatable, as certain in vitro studies have shown activity of ribavirin against RSV, but its usage for RSV infection is not routinely recommended in the management of lower respiratory tract disease because of the high cost, aerosol administration, and possible toxic effects among healthcare providers. 90 Zabofloxacin: is being developed as a new fluoroquinolone antibiotic that is a potent and selective inhibitor of the essential bacterial type II topoisomerases and topoisomerase IV and is indicated for community-acquired respiratory infections due to Gram-positive bacteria.
cord-312417-li41ng7v	2020	title: Rural community perceptions of antibiotic access and understanding of antimicrobial resistance: qualitative evidence from the Health and Demographic Surveillance System site in Matlab, Bangladesh OBJECTIVE: To explore factors and practices around access and use of antibiotics and understanding of antimicrobial resistance in rural communities in Bangladesh from a socio-cultural perspective. METHODS: This qualitative study comprises the second phase of the multi-country ABACUS (Antibiotic Access and Use) project in Matlab, Bangladesh. Multi-sectoral action is needed to confront the underlying social, economic, cultural and political drivers that impact on the access and use of antibiotic medicines in Bangladesh. The objective of this study is to explore factors and practices around access and use of antibiotics and understanding of antimicrobial resistance in rural communities in Bangladesh from a socio-cultural perspective. This study found that people in rural communities in Matlab were either not informed or knew little about appropriate access and use of antibiotic medicines.
cord-317410-hc06yo32	2018	However, a patient with a score of four should be tested by using rapid antigen detection test or throat culture, and empiric antibiotic therapy is required due to chance of streptococcal infection is high between 38% and 64% ( Figure 3 ) (61). To help physicians to prescribe the appropriate antibiotics for children and adults with streptococcus pharyngitis, Centres for Disease Control and Prevention (CDC), American Academy of Family Physicians (AAFP), and the Institute for Medical Research (IMR) have developed the clinical practice guidelines for respiratory tract infections (47, 64, 65) . According to the CDC, AAFP guidelines, and the National Antibiotic Guideline in Malaysia, antibiotics should be prescribed only to patients with group A streptococcal infection (Streptococcus pyogenes) which group A streptococcus usually cause symptoms including sore throat, fever more than 38 °C, exudates, nausea, vomiting, headache, stiff and swollen neck, abdominal pain, and tender enlarged cervical lymph nodes.
cord-322915-zrjx31ev	2009	Evidence of the importance of natural products in the discovery of leads for the development of drugs for the treatment of human diseases is provided by the fact that close to half of the best selling pharmaceuticals in 1991 were either natural products or their derivatives. In addition to the antibiotic-resistance problem, new families of anti-infective compounds are needed to enter the marketplace at regular intervals to tackle the new diseases caused by evolving pathogens. 28 Among the novel class of antimicrobial agents used in treating resistance to Gram-positive infections, we can also mention the cyclic lipopeptide antibiotic daptomycin produced by Streptomyces roseosporus. 44 Other applications include antitumor drugs, enzyme inhibitors, gastrointestinal motor stimulator agents, hypocholesterolemic drugs, ruminant growth stimulants, insecticides, herbicides, coccidiostats, antiparasitics vs coccidia, helminths and other pharmacological activities. Considering that animal health research and the development of new anti-infective product discovery have decreased, the discovery of new antibiotics has decreased over the past 15 years, with few new drug approvals.
cord-333334-90q1xkld	2019	title: Evaluation of a molecular point-of-care testing for viral and atypical pathogens on intravenous antibiotic duration in hospitalized adults with lower respiratory tract infection: a randomized clinical trial OBJECTIVES: The primary objective was to evaluate whether a molecular point-of-care test (POCT) for viral and atypical pathogens added to routine real-time PCR could reduce duration of intravenous antibiotics in hospitalized patients with lower respiratory tract infection (LRTI) compared with routine real-time PCR. The median and interquartile range of the primary outcome (duration of intravenous antibiotics) and secondary outcomes, including length of hospital stay, cost of intravenous antibiotics and cost of hospitalization, were calculated and the difference between intervention and control group was compared using the Wilcoxon rank-sum test. In conclusion, this study found the addition of molecular POCT testing to routine real-time PCR testing for respiratory viruses and atypical pathogens might help to reduce intravenous antibiotic use in LRTI patients without resulting in adverse outcomes.
cord-333535-pzjj2wxc	2015	Despite the limited number of enteric diseases in adult cattle that would benefit from antimicrobial therapy, surveys indicate that diarrhea is a relatively common reason for the use of antibiotics. If Salmonella are the main target of antimicrobial therapy in adult cattle with diarrhea, drug selection should ideally be based on the results of susceptibility testing using bacterial strains recovered from that particular dairy or feedlot. Despite this importance, the United States Department of Agriculture Dairy 2007 study shows a preweaned Antimicrobial Decision Making heifer calf mortality rate of 8.7% and reports that only 40% of farms can supply an adequate number of replacements from their own herd. The investigators concluded that amoxicillin had a significant effect on disease by decreasing mortality and number of scouring days; however, treatment success could not be predicted by whether the E coli cultured from rectal swabs was susceptible or resistant to the antimicrobial being used.
cord-333950-e0hd3iuu	2020	The authors call upon national and international policy makers, health agencies and healthcare professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR. 3, 4 The main driver is overuse and misuse of antibiotics in medicine and agriculture including unregulated over-the-counter sales, while global spread of resistant bacteria or resistance genes is attributed to poor infection prevention and control in healthcare facilities, and sub-optimal hygiene and sanitation in communities, confounded by poor infrastructure and weak governance. 94 Studies in day-care centers and schools in which hand hygiene was combined with cleaning and/or disinfection of environmental surfaces indicate a positive impact on illness rates and reduction in the use of antibiotics. The evidence set out in this paper suggests that, if combined with measures ensuring clean water and adequate sanitation, targeted hygiene practices in home and everyday life settings could make a significant contribution to tackling AMR through infection prevention and a consequential reduction in antibiotic prescribing.
cord-337955-4p6wbd0h	2020	The number of antibiotics dispensed each month by community pharmacists in England relating to NHS dental prescription forms from January 2018 to May 2020 is given in Figure 1 . 2 Antibiotics may have been used: • As a ''quick fix'' to avoid the life-time impact of an unnecessary extraction, in anticipation that AGPs might soon be permissible in general dental practices • Because dentists felt pressured by some patients for antibiotics, irrespective of their efficacy or appropriateness for treating toothache • Because of difficulties diagnosing a patient''s condition remotely prompting a ''just in case'' approach through concerns of life-threatening deterioration without treatment Finally, the NHS may have seen an influx in patients who might otherwise receive care privately, resulting in an increase in NHS dental prescriptions as, anecdotally, not all practices were open for telephone triage during April and May 2020. When this figure is combined with the average number of patients that we have seen each week, since lockdown was eased, and the local population, this enables us to quantify the risk of us seeing an undiagnosed COVID-19 patient in the practice.
cord-346308-9h2fk9qt	2020	The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. Within past years, pieces of evidence have shown mobilization of these resistance genes from the environment into pathogenic bacteria causing health risks to humans and animals and also, demonstrating a link between environmental and clinical resistance [123] . The HWW has been reported to have two overexpressed β-lactam-resistance genes (bla GES and bla OXA ) as compared with the water collected from other aquatic bodies, which could be correlated with antibiotic usage over the time in hospitals and discharge of the residues of antibiotics in the wastewater [176] . Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review
cord-346726-u7dhbmht	2018	We aimed to describe the potential benefit of new rapid molecular respiratory tests (MRT) in decreasing inappropriate antibiotic use among the inpatients presenting with influenza-like illness (ILI). It is time to increase the awareness about the viral etiology in respiratory tract infections (RTIs) and implement MRT in clinical practice. In adults, influenza virus, rhinovirus, adenovirus, respiratory syncytial virus (RSV), human coronavirus, and parainfluenza virus cause infections with considerable morbidity and mortality [1, 3] , and in infants, RSV is the most common reason for RTIs among hospitalized patients [4] . In this study, we aimed to describe the viral etiology in influenza-like illness (ILI) in children and adults and to show the benefit of new rapid molecular respiratory tests (MRT) in decreasing inappropriate antibiotic use. By using molecular rapid tests (MRT) in our hospital, inappropriate antibiotic use and also duration of inappropriate antibiotic use after the detection of virus was significantly decreased among inpatients.
cord-349775-zwslhjju	2011	The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR) assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs) would have an impact on antibiotic prescription rate in primary care clinical settings. Acute respiratory tract infections (ARTIs) represent a major global health burden [1] , and viruses cause a large proportion of ARTIs. Distinguishing bacterial ARTIs that require antibiotic treatment from viral ARTIs not needing an antibiotic prescription can be difficult on clinical grounds alone and causes unnecessary use of antibiotics, with the highest rates occurring in the primary care setting [2, 3] . The present study was designed to evaluate whether access to a multiplex RT-PCR method targeting thirteen viruses would have an impact on antibiotic prescription rates for ARTI in a primary care setting.
cord-351231-aoz5jbf1	2014	The value of the infectious disease practitioner is now magnified by the crisis of antibiotic resistance, the expanding consequences of international travel, the introduction of completely new pathogen diagnostics, and healthcare reform with emphasis on infection prevention and cost in dollars and lives. The point is that epidemics are the domain of infectious diseases and public health, with the expectation for management or prevention of outbreaks with requirements for detection, reporting, isolation, and case management. This began with a patient transferred from a New York City hospital with a KPC infection and became the source of an institutional outbreak that required extraordinary efforts to control, including a wall constructed to isolate cases, removal of plumbing (as a possible source), use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) molecular diagnostics to detect cases and carriers, hydrogen peroxide room aerosols, and "whole house" surveillance cultures. The new healthcare system should value infectious disease expertise based on its important role in addressing resistance and costs associated with nosocomial infections.