Antimicrobial Resistance & Wound Infections Li Yang Hsu 8 th April 2015
Potential Conflicts of Interest Research Funding: Pfizer Singapore AstraZeneca Janssen-Cilag Merck, Sharpe & Dohme Advisory Board: Doripenem (Janssen-Cilag) Adult pneumococcal vaccine & Tigecycline (Pfizer) Global Council: Tedizolid (Bayer) Conference sponsorships: Pfizer Singapore Janssen-Cilag Merck, Sharpe & Dohme
Overview Antimicrobial resistance Issues CRE in Singapore Wound infections Cases Discussion Antibiotic substitutes Conclusion
Antimicrobial Resistance Overview Review on AMR: http://amr-review.org/sites/default/files/report-52.15.pdf
Global/Local Issues
Ability to Prevent and/or Treat Bacterial Infections is a Building Block of Medicine Images from the Internet (including http://www.nature.com)
World Without Antibiotics Recreate Victorian times. Pneumonia = mass killer Childbirth = potentially life-threatening event Incurable tuberculosis = days of consumption. Basic surgery and dental procedures = impossible. Cascading effect on more complicated medical and surgical treatment. Cost of meat and livestock will increase.
What drives AMR? Plans and resources not comprehensive or coherent; poor accountability. Consumers and communities not engaged Surveillance systems weak or absent Systems for ensuring quality and supply of medicines inadequate Use of medicines inappropriate and irrational, including in animal husbandry Infection prevention and control poor Antimicrobials and diagnostics arsenal limited Research and development for diagnostics and medicines insufficient 7 April 2011 World Health Day No action today, no cure tomorrow
Well patient Undergoes treatment in hospital, i.e. Chemotherapy Surgery Immunosuppression Transplant Vulnerable patient Infected patient
Major Reasons for Antibiotic Prescription in Hospitals Urinary tract infections Pneumonia Skin and soft tissue infections.
Case I 35-year-old female. RTA with comminuted fracture of left forearm. Extensive debridement and bone grafting done. Wound breakdown 2 weeks after operation.
Case I Wound culture: Acinetobacter baumannii R to bactrim, ceftazidime, imipenem, meropenem, ciprofloxacin, gentamicin, ampicillin/sulbactam S to amikacin, polymyxin B, minocycline
Case I Repeated debridement. Bone involvement. PO Minocycline. After 5 weeks, wound culture: Acinetobacter baumannii R to bactrim, ceftazidime, imipenem, meropenem, ciprofloxacin, gentamicin, ampicillin/sulbactam, minocycline S to amikacin, polymyxin B
Case II 82-year-old female, multiple co-morbidities including renal impairment, wheelchair bound. Admitted to hospital for aspiration pneumonia. Develops a deep sacral sore. Spikes fever one day septic work-up done.
Case II Wound culture: MRSA ESBL+ Klebsiella pneumoniae Bacteroides fragilis Referred for choice of antimicrobial therapy.
Summary Table - MRSA Number of Isolates ST239 (%)* ST22 (%)* ST45 (%)* Others (%)** orfx (%) MupA (%) 1 157 8 (5.1%) 87 (55.4%) 13 (8.3%) 49 (31.2%) 2 (1.3%) 75 (47.8%) 2 31 1 (3.2%) 14 (45.2%) 3 (9.7%) 13 (41.9%) 0 (0%) 8 (25.8%) 3 10 1 (10.0%) 5 (50.0%) 1 (10.0%) 3 (30.0%) 0 (0%) 1 (10.0%) 4 44 2 (4.5%) 22 (50.0%) 11 (25.0%) 9 (20.5%) 0 (0%) 8 (18.2%) 5 76 3 (3.9%) 36 (47.4%) 9 (11.8%) 28 (36.8%) 2 (2.6%) 24 (31.6%) 6 159 22 (13.8%) 98 (61.6%) 5 (3.1%) 34 (21.4%) 15 (9.4%) 45 (28.3%) 7 188 18 (9.6%) 81 (43.1%) 23 (12.2%) 66 (35.1%) 11 (5.9%) 41 (25.8%) *MLST sequence types are assigned if MLVA profiles are >90% similar when mapped against existing profiles within the Bionumerics database. ** Includes isolates that have not typed using MLVA. Hon PY, et al. J Glob Antimicrob Resist. 2014.
Approach to Chronic Wounds 6 questions: Is infection present? Are systemic antibiotics necessary? Should treatment be IV or oral? What antibiotic(s) should be used? What is the duration of therapy? What circumstances are present that may impact therapy? Hernandez R. Dermatol Ther. 2006;19:326-37.
TIME Model Tissue Infection/Inflammation Moisture Edge of wound
http://www.woundsinternational.com/media/issues/122/files/content_86.pdf
Bacteria in the Wound All chronic wounds contain bacteria. Bacteria stimulate neutrophil activity may play necessary role in normal wound healing. Indiscriminate use of antibiotics to eliminate bacteria may be detrimental to normal wound healing. Contamination, colonization, critical colonization, infection. Biofilms. Hernandez R. Dermatol Ther. 2006;19:326-37.
Use of Systemic Antibiotics Chronic wounds + signs and symptoms of systemic or regional infections. Presence of osteomyelitis (may require bone biopsy or further radiological imaging to confirm). Non-healing local wound infection? Culturing of chronic wounds: Tissue biopsy Needle aspiration Curettage Swabs
Systemic Antibiotic Substitutes Topical antibiotics/antiseptics Maggots Phages Honey
Topical Antiseptics/Dressings Some topical antiseptics and antiseptic wound dressings are toxic to human cells. Little clinical evidence to differentiate between different types of antiseptics/dressings. Need for better research studies, including health economic analyses. Cooke J. Curr Opin Infect Dis. 2014;27:125-9.
Maggot Therapy for Chronic Wounds
Maggot Therapy for Chronic Wounds Shortened the healing time and improved wound healing in chronic cutaneous ulcers. (Re)infection rates and antibiotic usage not generally assessed. Limitations: Small number of studies only Considerable heterogeneity in studies Asian populations Sun X, et al. Int J Infect Dis. 2014;25:32-7.
Phages = viruses that target bacteria specifically. Extensively developed in Russia and Eastern Europe. Renewed interest in view of antimicrobial resistance. Phage Therapy Image from: Wikipedia.
Phage Therapy Fischetti V, et al. Nature Biotechnology. 2006;24:1508-11.
Honey
Honey (Meta-Analysis)
Honey (Meta-Analysis)
Conclusions Antimicrobial resistance is a global and local problem. It is induced by inappropriate use of antibiotics. Major inappropriate use of antibiotics: UTI Pneumonia Wound infections Chronic wounds: Careful assessment required. Not all bacterial cultures are significant. Consider the need for systemic antibiotics. Local therapy maggots, phages, etc.
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