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Concept: Antibiotics


Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or aiding investments in alternatives to antibiotics. In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1-34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3-15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth (P= 0.004). In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC. Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015. Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs. Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns.

Concepts: Infectious disease, Bacteria, Antibiotic resistance, Antibiotic, Microorganism, Penicillin, Clostridium difficile, Antibiotics


BACKGROUND: Over-prescribing of antibiotics is considered to result in increased morbidity and mortality from drug-resistant organisms. A resulting common wisdom is that it would be better for society if physicians would restrain their prescription of antibiotics. In this view, self-interest and societal interest are at odds, making antibiotic use a classic “tragedy of the commons”. METHODS AND FINDINGS: We developed two mathematical models of transmission of antibiotic resistance, featuring de novo development of resistance and transmission of resistant organisms. We analyzed the decision to prescribe antibiotics as a mathematical game, by analyzing individual incentives and community outcomes. CONCLUSIONS: A conflict of interest may indeed result, though not in all cases. Increased use of antibiotics by individuals benefits society under certain circumstances, despite the amplification of drug-resistant strains or organisms. In situations where increased use of antibiotics leads to less favorable outcomes for society, antibiotics may be harmful for the individual as well. For other scenarios, where a conflict between self-interest and society exists, restricting antibody use would benefit society. Thus, a case-by-case assessment of appropriate use of antibiotics may be warranted.

Concepts: Bacteria, Antibiotic resistance, Greek loanwords, Antibiotic, Microorganism, Individualism, Clostridium difficile, Antibiotics


Beta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta-lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram-negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs.

Concepts: Bacteria, Antibiotic resistance, Intensive care medicine, Antibiotic, Penicillin, Beta-lactam antibiotic, Beta-lactam, Antibiotics


Approaches to controlling emerging antibiotic resistance in health care settings have evolved over time. When resistance to broad-spectrum antimicrobials mediated by extended-spectrum β-lactamases (ESBLs) arose in the 1980s, targeted interventions to slow spread were not widely promoted. However, when Enterobacteriaceae with carbapenemases that confer resistance to carbapenem antibiotics emerged, directed control efforts were recommended. These distinct approaches could have resulted in differences in spread of these two pathogens. CDC evaluated these possible changes along with initial findings of an enhanced antibiotic resistance detection and control strategy that builds on interventions developed to control carbapenem resistance.

Concepts: Medicine, Bacteria, Antibiotic resistance, United Kingdom, Microorganism, Penicillin, Beta-lactam antibiotic, Antibiotics


Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

Concepts: Medicine, Bacteria, Species, Antibiotic resistance, Antibiotic, Microorganism, Penicillin, Antibiotics


Many respiratory tract infections are treated with macrolide antibiotics. Regulatory agencies warn that these antibiotics increase the risk of ventricular arrhythmia. We examined the 30-day risk of ventricular arrhythmia and all-cause mortality associated with macrolide antibiotics relative to nonmacrolide antibiotics.

Concepts: Respiratory system, Upper respiratory tract infection, Erythromycin, Macrolide, Antibiotics, Respiratory tract


Debate exists about whether agricultural versus medical antibiotic use drives increasing antibiotic resistance (AR) across nature. Both sectors have been inconsistent at antibiotic stewardship, but it is unclear which sector has most influenced acquired AR on broad scales. Using qPCR and soils archived since 1923 at Askov Experimental Station in Denmark, we quantified four broad-spectrum β-lactam AR genes (ARG; blaTEM, blaSHV, blaOXA and blaCTX-M) and class-1 integron genes (int1) in soils from manured (M) versus inorganic fertilised (IF) fields. “Total” β-lactam ARG levels were significantly higher in M versus IF in soils post-1940 (paired-t test; p < 0.001). However, dominant individual ARGs varied over time; blaTEM and blaSHV between 1963 and 1974, blaOXA slightly later, and blaCTX-M since 1988. These dates roughly parallel first reporting of these genes in clinical isolates, suggesting ARGs in animal manure and humans are historically interconnected. Archive data further show when non-therapeutic antibiotic use was banned in Denmark, blaCTX-M levels declined in M soils, suggesting accumulated soil ARGs can be reduced by prudent antibiotic stewardship. Conversely, int1 levels have continued to increase in M soils since 1990, implying direct manure application to soils should be scrutinized as part of future stewardship programs.

Concepts: Bacteria, Agriculture, Antibiotic resistance, Soil, Antibiotic, Antibiotics, Manure, Alternate reality game


Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death.

Concepts: Cardiology, Cardiac arrest, Sudden cardiac death, Erythromycin, Macrolide, Azithromycin, Antibiotics


Reported penicillin allergy rarely reflects penicillin intolerance. Failure to address inpatient penicillin allergies results in more broad-spectrum antibiotic use, treatment failures, and adverse drug events.

Concepts: Microbiology, Allergy, Aspirin, Adverse drug reaction, Antibiotic, Penicillin, Antibiotics, Broad-spectrum antibiotic


BACKGROUND AND OBJECTIVE:Narrow-spectrum antibiotics are recommended as the first-line agent for children hospitalized with community-acquired pneumonia (CAP). There is little scientific evidence to support that this consensus-based recommendation is as effective as the more commonly used broad-spectrum antibiotics. The objective was to compare the effectiveness of empiric treatment with narrow-spectrum therapy versus broad-spectrum therapy for children hospitalized with uncomplicated CAP.METHODS:This multicenter retrospective cohort study using medical records included children aged 2 months to 18 years at 4 children’s hospitals in 2010 with a discharge diagnosis of CAP. Patients receiving either narrow-spectrum or broad-spectrum therapy in the first 2 days of hospitalization were eligible. Patients were matched by using propensity scores that determined each patient’s likelihood of receiving empiric narrow or broad coverage. A multivariate logistic regression analysis evaluated the relationship between antibiotic and hospital length of stay (LOS), 7-day readmission, standardized daily costs, duration of fever, and duration of supplemental oxygen.RESULTS:Among 492 patients, 52% were empirically treated with a narrow-spectrum agent and 48% with a broad-spectrum agent. In the adjusted analysis, the narrow-spectrum group had a 10-hour shorter LOS (P = .04). There was no significant difference in duration of oxygen, duration of fever, or readmission. When modeled for LOS, there was no difference in average daily standardized cost (P = .62) or average daily standardized pharmacy cost (P = .26).CONCLUSIONS:Compared with broad-spectrum agents, narrow-spectrum antibiotic coverage is associated with similar outcomes. Our findings support national consensus recommendations for the use of narrow-spectrum antibiotics in children hospitalized with CAP.

Concepts: Cohort study, Bacteria, Pneumonia, Hospital, Antibiotic, Empiric therapy, Antibiotics, Broad-spectrum antibiotic