Global Status of Antimicrobial Resistance with a Focus on Nepal John Ferguson, John Hunter Hospital, University of Newcastle, NSW, Australia Infectious Diseases Physician and Medical Microbiologist SIMON Conference, Kathmandu, April 2015
Australian perspective John Hunter Hospital, Newcastle University of Newcastle
Overview 1. The situation 2. What part can physicians take in control of AMR? 3. Practical and therapeutic options that will be effective
Massive global increases in AMR Excellent summary of current situation http://www.thelancet.com/commissions/antibi otic-resistance-the-need-for-global-solutions
Massive global increases in AMR Excellent summary of current Nepali situation based on published research and other information http://cddep.org/blog/posts /garp_nepal_painting_full_pi cture_antibiotic_resistance
Bacterial perspective 3.5 billion years of evolutionary diversification Estimated 10 21 bacteria; one billion progeny/ day Adapted to innumerable niches Sense their environment, exhibit cooperative behaviour and adaptive stress responses Antibiotic resistance genes are ancient Humans carry 2-3 kg of bacterial biomass acquired from diverse sources
How does resistance arise? 1. mutational change in bacterial chromosome with clonal expansion of a resistant subpopulation AND/OR 2. horizontal transfer of new resistance gene(s) from another bacterial species by direct transfer and recombination Antibiotic exposure increases the rate of both processes Antibiotics select and promote growth of resistant subpopulations
Reducing use reduces resistance: evidence from the United Kingdom Slides courtesy of Neil Woodford, HPA 2012
Monthly changing infection control practices and antibiotic use independently contributed to the later hospital MRSA incidence (78% of the variance in MRSA incidence was explained by the time-series model). Improving infection control AND improving (reducing) antibiotic use INDEPENDENTLY REDUCE INFECTION RATES
WHO Draft Global Action Plan 2015 Revised March 2015 for World Health Assembly next month All nations will have to draft their own 2 year action plansprinciples- Whole of society engagement including a One health approach Prevention first- emphasis on infection control Access- need to preserve equitable access to antimicrobials Sustainability Major objectives 1. Improve awareness and understanding of AMR 2. Strengthen knowledge and evidence base through surveillance and research 3. Reduce the incidence of infection 4. Optimise use of antimicrobials in human and animal health 5. Develop economic case for sustainable investment in new medicines, microbiology and diagnostic tools, vaccines etc
Overview 1. The situation 2. What part can physicians take in control of AMR? 3. Practical and therapeutic options that will be effective
G Hardin - 1968 Without collective approaches that protect resources held in common (eg. antibiotics) inexorable degradation occurs (= antimicrobial resistance) No technical solution will substitute. Stewardship required
Physicians need to become stewards Stewardship is an ethic that embodies the responsible planning and management of resources. Wikipedia There is an urgent need for all of us to collaborate to reduce AMR and take on necessary leadership and advocacy roles. We have the agency (influence) and the scope to change patient management in ways that will reduce the impact of AMR on our patients and the community
Antimicrobial Stewardship in Australian Hospitals Comprehensive practical reference resource http://www.safetyandq uality.gov.au/ourwork/healthcareassociatedinfection/antimicrobialstewardship/book/
Practical and Therapeutic Options: infection control www.react.org
Standard precautions : the basis for protecting ALL patients & staff
Hand disinfection saves lives- the first demonstration Vienna: intervention: Students and doctors required to clean their hands with a chlorinated lime solution when entering the labour room in particular when moving from the autopsy to the labour room
Abdomen of an MRSA positive patient examined by a physician Hand cultured for MRSA before and after using alcohol hand rub Donskey C and Eckstein B. N Engl J Med 2009;360:e3 MRSA= methicillin-resistant Staphylococcus aureus
WHO: 5 Moments for Hand Hygiene standard http://www.who.int/gpsc/tools/five_ moments/en/
Alcohol-based hand rub: point of care Walk the talk lead by example Use rub BEFORE and AFTER every patient contact Teach patients to use the rub
NSW HNE- Impact of increasing HH on healthcare MRSA bloodstream infections and mortality Deaths within 30 days
Practical and Therapeutic Options: using antibiotics properly www.react.org
Therapeutic factors promoting antibiotic resistance 1. Antibiotic selective pressure Number of patients exposed (volume of use) Breadth of spectrum Duration of use 2. Inadequate dosing
Point prevalence surveys of usage Study how antibiotics are being used in your unit Document diagnosis, drugs, dosage, duration and indication Assess appropriateness, bug-drug mismatches, compliance against guidelines; involve other local experts including your microbiologist in the analysis Drive change reduce or eliminate pointless use, develop and implement local guidelines
National Antimicrobial Prescribing Survey (NAPS)- Australia Online point prevalence survey tool survey with advanced reporting capability Scope for access from Nepal with arrangement
Eliminate unnecessary use Patients may receive antibiotics for extended post operative prophylaxis or for just in case situations where there is little actual evidence of infection These exposures put patients at great risk of acquiring resistant organisms and should be avoided (Antibiotics do not protect patients from poor hygiene) Barza M et al. Clin Infect Dis. 2002 Jun 1;34 Suppl 3:S126-30. Excess infections due to antimicrobial resistance: the "Attributable Fraction".
Rational empirical antibiotic use Evaluate likelihood of sepsis by presence of SIRS, other organ system dysfunction Be prepared to withhold antibiotics if there is not a strong case and severe sepsis is absent Don t neglect pre-antibiotic micro tests Select empirical antibiotic(s) based on local guidelines and AMR incidence Always document the antibiotic indication in the patient record
Aminoglycosides- good choice for potential Gram negative sepsis Rapidly bactericidal if given at sufficient dose, (concentration-dependent kill) Avoid prolonged usage ( > 3 days ) in order to reduce toxicity Base choice of agent on local patterns of susceptibility Use in combination therapy if local aminoglycoside susceptibility < 80%. Australian dosing recommendations: 4-5mg/kg (ideal bwt), 7mg/kg (septic shock), 3 daily doses (normal renal fx), 1 or 2 doses ( impaired initial renal function).
Vancomycin: good choice for broad spectrum Gram pos cover in sepsis Slow onset of action Standard of care (Australia) - give loading dose of 25-30mg/kg (based on actual body weight) Then give 1.5g 12-hrly for GFR>90, lower dosing for patients with renal failure Avoid linezolid for empirical use for this purpose
Situations where narrow spectrum empirical agents are feasible Acute on chronic airflow limitation doxycycline or amoxycillin (benzylpenicillin) max 3 days Community acquired pneumonia (mild-moderate) benzylpenicillin monotherapy Gram stain of well-collected sputum provides reliable rapid guidance (extensive evidence) Skin/soft tissue infection without sepsis (culture, MRSA prevalence?) Cochrane Database Syst Rev. 2012 Dec Antibiotics for exacerbations of chronic obstructive pulmonary disease. Postma et al. Antibiotic treatment strategies for community-acquired pneumonia in adults N Engl J Med. 2015 Apr 2;372(14):1312-23.
Other alternatives for MRSA skin/soft tissue infection No antibiotics limited evidence that antimicrobials benefit patient with boils Depending on susceptibility, oral cotrimoxazole, doxycycline, clindamycin, erythromycin may be used at correct dose (avoid if systemic sepsis present) Don t chase pseudomonas and other Gram negatives in chronic ulcers or diabetic feet Avoid use of quinolones for treatment of Gram positive infection - reserve for Gram negative infection
Post-empiric management: evaluate at 48-72 hrs Response to treatment: Clinical temperature, control of sepsis, evaluation of source Laboratory WCC, CRP, culture results Assessment Is there another non-infective cause? Is antibiotic treatment still indicated? If ongoing treatment indicated consider early switch to oral
Limit durations of treatment A very effective way to reduce selective pressure Shorter duration treatments are feasible with: community pneumonia (3-5d)- extensive studies Intensive care unit pneumonia (7d) Localised UTI (3 days), UTI with sepsis (7-10d) Intra-abdominal sepsis with source controlled (1-7d), Local guidelines need to specify recommended durations Paterson-D et al. Strategies for Reduction in Duration of Antibiotic Use in Hospitalized Patients Clinical Infectious Diseases 2011: 52: 1232
We can make a real difference! 1. Take infection control practices seriously- Semmelweis was right - hand hygiene saves lives 2. Learn about your local AMR problem talk to your microbiologist 3. Critically examine the antibiotic prescribing practice in your unit point prevalence survey 4. Formulate local guidelines 5. Work with your laboratory to improve diagnostics and resistance testing 6. Walk the talk- become stewards, follow the guidelines, raise awareness everywhere
Definition of insanity: doing the same thing over and over again and expecting different results. Albert Einstein