- Email: [email protected]
Antibiotic stewardship hits a home run for patients
Comment
In conclusion, the study by Steinhoff and colleagues supports previous randomised trials and brings major new data, especially concerning birthweight, for the implementation of large-scale maternal immunisation in resource-limited countries. The results justify the financing of such immunisation programmes.
1 2 3 4
Paul Loubet, *Odile Launay Université Paris Diderot, Sorbonne Paris Cité, Paris, France (PL); Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et Tropicales, Paris, France (PL); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (OL); Assistance Publique–Hôpitaux de Paris (AP–HP), DHU risks and pregnancy, CIC Cochin Pasteur, Hôpital Cochin, 75679 Paris, France (OL); Inserm, CIC 1417, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Paris, France (OL); and UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Paris, France (OL) [email protected] OL has received personal fees from Sanofi Pasteur; grants, personal fees, and non-financial support from Pfizer, Janssen, and Sanofi Pasteur-Merck Sharp & Dohme; and grants, and non-financial support from GlaxoSmithKline. PL has received personal fees and non-financial support from Pfizer; and non-financial support from Sanofi Pasteur.
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Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998; 148: 1094–102. Neuzil KM, Mellen BG, Wright PF, Mitchel EF, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000; 342: 225–21. Nair H, Brooks WA, Katz M, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet 2011; 378: 1917–30. Loubet P, Kerneis S, Anselem O, Tsatsaris V, Goffinet F, Launay O. Should expectant mothers be vaccinated against flu? A safety review. Expert Opin Drug Saf 2014; 13: 1709–20. Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 2008; 359: 1555–64. Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014; 371: 918–31. Tapia MD, Sow SO, Tamboura B, et al. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis 2016; 16: 1026–35. Steinhoff MC, Katz J, Englund JA, et al. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, placebo-controlled trial. Lancet Infect Dis 2017; published online May 15. http://dx.doi. org/10.1016/S1473-3099(17)30252-9. UNICEF. Tracking progress on child and maternal nutrition: a survival and development priority. New York: UNICEF; 2009. https://www.unicef.org/ publications/files/Tracking_Progress_on_Child_and_Maternal_Nutrition_ EN_110309.pdf (accessed May 5, 2017).
Julien Behal/PA Wire/PA Images
Antibiotic stewardship hits a home run for patients
Published Online June 16, 2017 http://dx.doi.org/10.1016/ S1473-3099(17)30344-4 See Articles page 990
892
The 70th World Health Assembly in May, 2017, marked the deadline for publication by member states of their national action plans to combat drug-resistant infections, with particular focus on antibiotic-resistant bacteria. Antibiotic stewardship forms a crucial intervention in such plans, supporting access to, and appropriate use of, antibiotics across human and animal health. Antibiotic stewardship programmes are recommended for all health-care facilities.1–4 Frontline stewards observe the daily effects of antibiotic-resistant bacteria on morbidity and mortality, yet many healthcare providers, managers, and policy makers still challenge the evidence that stewardship programmes favourably affect rates of bacterial resistance. David Baur and colleagues5 did the first systematic review and meta-analysis of the effect of inpatient stewardship programmes on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile. To paraphrase a saying from baseball, their findings show that antibiotic stewardship programmes hit the ball out of the ballpark for the game-winning run. Baur and colleagues show the
effectiveness of antibiotic stewardship in reducing the incidence of infections and colonisation with multidrug-resistant Gram-negative bacteria, extendedspectrum β-lactamase-producing and carbapenemresistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus, and C difficile. The finding from the study5 that the greatest benefit from stewardship programmes occurs when they are implemented alongside programmes that improve infection control through hand hygiene, highlights the need for governments to develop national action plans that co-prioritise antibiotic stewardship and infection prevention. Such plans need to be converted into concrete action, which will require considerable financial input, especially in low-income and middleincome countries where health systems face substantial budgetary restrictions. In this respect, it is fine to talk the talk, but countries and the global community now need to step up and walk the walk when it comes to financing national action plans.6 The necessity for national action plans to co-develop antibiotic stewardship and infection prevention www.thelancet.com/infection Vol 17 September 2017
Comment
programmes re-affirms the power of a multidisciplinary approach. A winning team knows that teamwork is what makes the dream work; clinicians, infection prevention professionals, pharmacists, microbiologists, nurses, and an ever-expanding number of health-care professionals involved at the clinical interface form a whole that is greater than the sum of its parts. Only five of the 32 studies included in Baur and colleagues’ meta-analysis were from low-income or middle-income countries, where multidisciplinary teams are rarely found outside of central hospitals. In these settings, we need to re-examine our perception of what an antibiotic stewardship programme looks like. The success of pharmacist-led stewardship programmes7 highlights a model that builds stewardship teams around this key cadre of health professional. And what of stewardship programmes at the community level? We need to look to non-traditional stewards, such as community health workers and members of the public, in settings where health-care professionals are a scarce resource.8–10 Non-traditional stewards need to join us in a partnership that looks beyond what can be offered in high-resource settings. Decreasing antibiotic resistance while preserving the effectiveness of antibiotics is the dream and antibiotic stewardship is the team captain. Baur and colleagues have provided the ammunition to convey this important message to antibiotic stewardship naysayers, policy makers, and stakeholders. The results of Baur and colleagues’ meta-analysis are an important advocacy tool, and one that we should use in support of developing winning teams. If we get antibiotic stewardship right, the real winner will be the patient who avoids infection by a drug-resistant bacterium
or C difficile, now and in the future, as we preserve antibiotics for the generations to come. *Debra A Goff, Marc Mendelson The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA (DAG); and Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa (MM) [email protected] We declare no competing interests. 1
CDC. Core elements of hospital antibiotic stewardship programs. https://www.cdc.gov/getsmart/healthcare/implementation/coreelements.html (accessed May 7, 2017). 2 Goff DA, Kullar R, Bauer KA, File TM Jr. Eight habits of highly effective antimicrobial stewardship programs to meet the joint commission standard for hospitals. Clin Infect Dis 2017; 64: 1134–39. 3 Federation of Infectious Diseases Societies of southern Africa. Mission statement of the South African antibiotic stewardship programme. http://www.fidssa.co.za/SAASP (accessed May 7, 2017). 4 UN General Assembly. Resolution A/RES/71/3. Political declaration of the high-level meeting of the General Assembly on antimicrobial resistance. New York, NY: United Nations, 2016. http://www.un.org/en/ga/search/ view_doc.asp?symbol=A/RES/71/3 (accessed May 6, 2017). 5 Baur D, Gladstone BP, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis 2017; published online June 16. http://dx.doi.org/10.1016/S1473-3099(17)30325-0 6 Mendelson M, Dar OA, Hoffman SJ, Laxminarayan R, Mpundu MM, Røttingen JA. A global antimicrobial conservation fund for low- and middle-income countries. Int J Infect Dis 2016; 51: 70–72. 7 Brink AJ, Messina A, Feldman C, et al, for the Netcare Antimicrobial Stewardship Study Alliance. Antimicrobial stewardship across 47 South African hospitals: an implementation study. Lancet Infect Dis 2016; 16: 1017–25. 8 Gill CJ, Phiri-Mazala G, Guerinea NG, et al. Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study. BMJ 2011; 342: d346. 9 Zaidi AKM, Baqui AH, Qazi SA, et al. Scientific rationale for study design of community-based simplified antibiotic therapy trials in newborns and young infants with clinically diagnosed severe infections or fast breathing in South Asia and sub-Saharan Africa. Pediatr Infect Dis J 2013; 32 (suppl 1): S7–11. 10 Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet 1999; 354: 1955–61.
International Surviving Sepsis Campaign guidelines 2016: the perspective from low-income and middle-income countries In the most recent international Surviving Sepsis Campaign guidelines, Rhodes and colleagues1 excellently outline evidence-based management of patients with sepsis and septic shock. Of note, however, is that most of the world’s population resides in low-income and middleincome countries (LMICs), where the burden of sepsis is enormous, outcomes are often poor, and socioeconomic consequences are dire.2 Of the 655 references supporting www.thelancet.com/infection Vol 17 September 2017
the new sepsis guidelines, only a few pertain to studies in LMICs (about 10%).1 This disparity raises concerns that the challenges and problems inherent to LMICs remain inadequately addressed. The guidelines, for example, mainly focus on management of bacterial and fungal sepsis as most frequently encountered in high-income countries. Strikingly, the specific diagnosis and management of sepsis due to pathogens commonly 893
In conclusion, the study by Steinhoff and colleagues supports previous randomised trials and brings major new data, especially concerning birthweight, for the implementation of large-scale maternal immunisation in resource-limited countries. The results justify the financing of such immunisation programmes.
1 2 3 4
Paul Loubet, *Odile Launay Université Paris Diderot, Sorbonne Paris Cité, Paris, France (PL); Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et Tropicales, Paris, France (PL); Université Paris Descartes, Sorbonne Paris Cité, Paris, France (OL); Assistance Publique–Hôpitaux de Paris (AP–HP), DHU risks and pregnancy, CIC Cochin Pasteur, Hôpital Cochin, 75679 Paris, France (OL); Inserm, CIC 1417, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Paris, France (OL); and UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Paris, France (OL) [email protected] OL has received personal fees from Sanofi Pasteur; grants, personal fees, and non-financial support from Pfizer, Janssen, and Sanofi Pasteur-Merck Sharp & Dohme; and grants, and non-financial support from GlaxoSmithKline. PL has received personal fees and non-financial support from Pfizer; and non-financial support from Sanofi Pasteur.
5 6 7
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9
Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998; 148: 1094–102. Neuzil KM, Mellen BG, Wright PF, Mitchel EF, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000; 342: 225–21. Nair H, Brooks WA, Katz M, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet 2011; 378: 1917–30. Loubet P, Kerneis S, Anselem O, Tsatsaris V, Goffinet F, Launay O. Should expectant mothers be vaccinated against flu? A safety review. Expert Opin Drug Saf 2014; 13: 1709–20. Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 2008; 359: 1555–64. Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014; 371: 918–31. Tapia MD, Sow SO, Tamboura B, et al. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis 2016; 16: 1026–35. Steinhoff MC, Katz J, Englund JA, et al. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, placebo-controlled trial. Lancet Infect Dis 2017; published online May 15. http://dx.doi. org/10.1016/S1473-3099(17)30252-9. UNICEF. Tracking progress on child and maternal nutrition: a survival and development priority. New York: UNICEF; 2009. https://www.unicef.org/ publications/files/Tracking_Progress_on_Child_and_Maternal_Nutrition_ EN_110309.pdf (accessed May 5, 2017).
Julien Behal/PA Wire/PA Images
Antibiotic stewardship hits a home run for patients
Published Online June 16, 2017 http://dx.doi.org/10.1016/ S1473-3099(17)30344-4 See Articles page 990
892
The 70th World Health Assembly in May, 2017, marked the deadline for publication by member states of their national action plans to combat drug-resistant infections, with particular focus on antibiotic-resistant bacteria. Antibiotic stewardship forms a crucial intervention in such plans, supporting access to, and appropriate use of, antibiotics across human and animal health. Antibiotic stewardship programmes are recommended for all health-care facilities.1–4 Frontline stewards observe the daily effects of antibiotic-resistant bacteria on morbidity and mortality, yet many healthcare providers, managers, and policy makers still challenge the evidence that stewardship programmes favourably affect rates of bacterial resistance. David Baur and colleagues5 did the first systematic review and meta-analysis of the effect of inpatient stewardship programmes on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile. To paraphrase a saying from baseball, their findings show that antibiotic stewardship programmes hit the ball out of the ballpark for the game-winning run. Baur and colleagues show the
effectiveness of antibiotic stewardship in reducing the incidence of infections and colonisation with multidrug-resistant Gram-negative bacteria, extendedspectrum β-lactamase-producing and carbapenemresistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus, and C difficile. The finding from the study5 that the greatest benefit from stewardship programmes occurs when they are implemented alongside programmes that improve infection control through hand hygiene, highlights the need for governments to develop national action plans that co-prioritise antibiotic stewardship and infection prevention. Such plans need to be converted into concrete action, which will require considerable financial input, especially in low-income and middleincome countries where health systems face substantial budgetary restrictions. In this respect, it is fine to talk the talk, but countries and the global community now need to step up and walk the walk when it comes to financing national action plans.6 The necessity for national action plans to co-develop antibiotic stewardship and infection prevention www.thelancet.com/infection Vol 17 September 2017
Comment
programmes re-affirms the power of a multidisciplinary approach. A winning team knows that teamwork is what makes the dream work; clinicians, infection prevention professionals, pharmacists, microbiologists, nurses, and an ever-expanding number of health-care professionals involved at the clinical interface form a whole that is greater than the sum of its parts. Only five of the 32 studies included in Baur and colleagues’ meta-analysis were from low-income or middle-income countries, where multidisciplinary teams are rarely found outside of central hospitals. In these settings, we need to re-examine our perception of what an antibiotic stewardship programme looks like. The success of pharmacist-led stewardship programmes7 highlights a model that builds stewardship teams around this key cadre of health professional. And what of stewardship programmes at the community level? We need to look to non-traditional stewards, such as community health workers and members of the public, in settings where health-care professionals are a scarce resource.8–10 Non-traditional stewards need to join us in a partnership that looks beyond what can be offered in high-resource settings. Decreasing antibiotic resistance while preserving the effectiveness of antibiotics is the dream and antibiotic stewardship is the team captain. Baur and colleagues have provided the ammunition to convey this important message to antibiotic stewardship naysayers, policy makers, and stakeholders. The results of Baur and colleagues’ meta-analysis are an important advocacy tool, and one that we should use in support of developing winning teams. If we get antibiotic stewardship right, the real winner will be the patient who avoids infection by a drug-resistant bacterium
or C difficile, now and in the future, as we preserve antibiotics for the generations to come. *Debra A Goff, Marc Mendelson The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA (DAG); and Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa (MM) [email protected] We declare no competing interests. 1
CDC. Core elements of hospital antibiotic stewardship programs. https://www.cdc.gov/getsmart/healthcare/implementation/coreelements.html (accessed May 7, 2017). 2 Goff DA, Kullar R, Bauer KA, File TM Jr. Eight habits of highly effective antimicrobial stewardship programs to meet the joint commission standard for hospitals. Clin Infect Dis 2017; 64: 1134–39. 3 Federation of Infectious Diseases Societies of southern Africa. Mission statement of the South African antibiotic stewardship programme. http://www.fidssa.co.za/SAASP (accessed May 7, 2017). 4 UN General Assembly. Resolution A/RES/71/3. Political declaration of the high-level meeting of the General Assembly on antimicrobial resistance. New York, NY: United Nations, 2016. http://www.un.org/en/ga/search/ view_doc.asp?symbol=A/RES/71/3 (accessed May 6, 2017). 5 Baur D, Gladstone BP, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis 2017; published online June 16. http://dx.doi.org/10.1016/S1473-3099(17)30325-0 6 Mendelson M, Dar OA, Hoffman SJ, Laxminarayan R, Mpundu MM, Røttingen JA. A global antimicrobial conservation fund for low- and middle-income countries. Int J Infect Dis 2016; 51: 70–72. 7 Brink AJ, Messina A, Feldman C, et al, for the Netcare Antimicrobial Stewardship Study Alliance. Antimicrobial stewardship across 47 South African hospitals: an implementation study. Lancet Infect Dis 2016; 16: 1017–25. 8 Gill CJ, Phiri-Mazala G, Guerinea NG, et al. Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study. BMJ 2011; 342: d346. 9 Zaidi AKM, Baqui AH, Qazi SA, et al. Scientific rationale for study design of community-based simplified antibiotic therapy trials in newborns and young infants with clinically diagnosed severe infections or fast breathing in South Asia and sub-Saharan Africa. Pediatr Infect Dis J 2013; 32 (suppl 1): S7–11. 10 Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet 1999; 354: 1955–61.
International Surviving Sepsis Campaign guidelines 2016: the perspective from low-income and middle-income countries In the most recent international Surviving Sepsis Campaign guidelines, Rhodes and colleagues1 excellently outline evidence-based management of patients with sepsis and septic shock. Of note, however, is that most of the world’s population resides in low-income and middleincome countries (LMICs), where the burden of sepsis is enormous, outcomes are often poor, and socioeconomic consequences are dire.2 Of the 655 references supporting www.thelancet.com/infection Vol 17 September 2017
the new sepsis guidelines, only a few pertain to studies in LMICs (about 10%).1 This disparity raises concerns that the challenges and problems inherent to LMICs remain inadequately addressed. The guidelines, for example, mainly focus on management of bacterial and fungal sepsis as most frequently encountered in high-income countries. Strikingly, the specific diagnosis and management of sepsis due to pathogens commonly 893