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Laxminarayan R.,Center for Disease Dynamics | Laxminarayan R.,Princeton Environmental Institute
Science | Year: 2014

Antibiotic effectiveness is a natural societal resource that is diminished by antibiotic use. As with other such assets, keeping it available requires both conservation and innovation. Conservation encompasses making the best use of current antibiotic effectiveness by reducing demand through vaccination, infection control, diagnostics, public education, incentives for clinicians to prescribe fewer antibiotics, and restrictions on access to newer, last-resort antibiotics. Innovation includes improving the efficacy of current drugs and replenishing effectiveness by developing new drugs. In this paper, I assess the relative benefits and costs of these two approaches to maintaining our ability to treat infections.Copyright © 2014 by the American Association for the Advancement of Science; all rights reserved.

Laxminarayan R.,Center for Disease Dynamics
American Journal of Epidemiology | Year: 2013

Methicillin-resistant Staphylococcus aureus (MRSA) can cause major illness and death and impose serious economic costs on patients and hospitals. Community-associated MRSA (CA-MRSA) is a growing problem in US hospitals, which are already dealing with high levels of hospital-associated MRSA (HA-MRSA), but little is known about how patient age and seasonal differences in the incidence of these 2 forms of MRSA affect the epidemic. By using national data on hospitalizations and antibiotic resistance, we estimated the magnitude and trends in annual S. aureus and MRSA hospitalization rates from 2005-2009 by patient age, infection type, and resistance phenotype (CA-MRSA vs. HA-MRSA). Although no statistically significant increase in the hospitalization rate was seen over the study period, the total number of infections increased. In 2009, there were an estimated 463,017 (95% confidence interval: 441,595, 484,439) MRSA-related hospitalizations at a rate of 11.74 (95% confidence interval: 11.20, 12.28) per 1,000 hospitalizations. We observed significant differences in infection type by age, with HA-MRSA-related hospitalizations being more common in older individuals. We also noted significant seasonality in incidence, particularly in children, with CA-MRSA peaking in the late summer and HA-MRSA peaking in the winter, which may be caused by seasonal shifts in antibiotic prescribing patterns. © 2013 The Author.

Morgan D.J.,University of Maryland, Baltimore | Okeke I.N.,Haverford College | Laxminarayan R.,Center for Disease Dynamics | Laxminarayan R.,Princeton University | And 2 more authors.
The Lancet Infectious Diseases | Year: 2011

In much of the world antimicrobial drugs are sold without prescription or oversight by health-care professionals. The scale and effect of this practice is unknown. We systematically reviewed published works about non-prescription antimicrobials from 1970-2009, identifying 117 relevant articles. 35 community surveys from five continents showed that non-prescription use occurred worldwide and accounted for 19-100% of antimicrobial use outside of northern Europe and North America. Safety issues associated with non-prescription use included adverse drug reactions and masking of underlying infectious processes. Non-prescription use was common for non-bacterial disease, and antituberculosis drugs were available in many areas. Antimicrobial-resistant bacteria are common in communities with frequent non-prescription use. In a few settings, control efforts that included regulation decreased antimicrobial use and resistance. Non-prescription antimicrobial and antituberculosis use is common outside of North America and northern Europe and must be accounted for in public health efforts to reduce antimicrobial resistance. © 2011 Elsevier Ltd.

Kouyos R.,Princeton University | Kouyos R.,University of Zurich | Klein E.,Princeton University | Klein E.,Johns Hopkins University | And 2 more authors.
PLoS Pathogens | Year: 2013

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of morbidity and mortality in both hospitals and the community. Traditionally, MRSA was mainly hospital-associated (HA-MRSA), but in the past decade community-associated strains (CA-MRSA) have spread widely. CA-MRSA strains seem to have significantly lower biological costs of resistance, and hence it has been speculated that they may replace HA-MRSA strains in the hospital. Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects. Here we assess the impact of competition between HA- and CA-MRSA using epidemiological models which integrate realistic data on drug-usage frequencies, resistance profiles, contact, and age structures. By explicitly accounting for the differing antibiotic usage frequencies in the hospital and the community, we find that coexistence between the strains is a possible outcome, as selection favors CA-MRSA in the community, because of its lower cost of resistance, while it favors HA-MRSA in the hospital, because of its broader resistance spectrum. Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible. Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome. © 2013 Kouyos et al.

Teillant A.,Princeton University | Gandra S.,Center for Disease Dynamics | Barter D.,Center for Disease Dynamics | Morgan D.J.,Center for Disease Dynamics | And 4 more authors.
The Lancet Infectious Diseases | Year: 2015

Background: The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. Methods: We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence-eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA. Findings: We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120 000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40 000 for a 10% reduction in efficacy to 280 000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15 000 for a 70% reduction). We estimated that every year, 13 120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA. Interpretation: Increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy. More data are needed to establish how antibiotic prophylaxis recommendations should be modified in the context of increasing rates of resistance. Funding: DRIVE-AB Consortium. © 2015 Elsevier Ltd.

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