Clinical case discussion - myasthenia gravis

ccd myasthenia gravis

1. Clinical Case Discussion Dr shinde viraj ashok Junior resident 3 Department of pharmacology

2. Patient details Name - Shubhangi Sheshrao Deshbhartar Age / Sex – 22yrs / F Reg no – 1226958 Diagnosis – Myasthenia gravis with hypothyroidism

3. S/B AP ↓ ENT 2 on 23/07/2016 Chief complaints Dysphagia Findings Oral cavity – WNL Indirect laryngoscopy - WNL k/c/o myasthenia gravis on medication since 1 year Advise Physician opinion

4. S/B Physician ↓ 2 on 23/07/2016 Referred from ENT Chief complaints k/c/o myasthenia gravis with hypothyroidism since 2 year Diplopia since 1 ½ year Slurring speech since 1 ½ month Weakness of both upper & lower limb since 1 ½ month Difficulty in deglutition with regurgitation since 8 days O/E P – 80 bpm BP – 100/60 mm of Hg S/E RS & CVS – WNL CNS – Conscious Oriented Motor system Nutrition – average Power – 5/5 Hand grip – 60% DTR 2+ Plantar – b/l flexor

5. S/B Physician ↓ 6 on 23/07/2016 No h/o ptosis Tab thyroxine 100µg Tab azaron ( azathioprine )50mg OD Tab omnacortil (Prednisolone)5 mg OD Advice Please admit patient in Female Medicine Ward

6. S/B Lecturer / AP on 23/07/2016 at 2 pm GC – Moderate Afebrile P- 78bpm RS – Clear Vitals – Stable Advice Plasmapheresis Nephro call Same treatment was continued on 24/07/2016 Treatment 1 point DNS Inj neostigmine 0.5mg BD Inj atropine 0.6mg before neostigmine Tab omnacortil (Prednisolone) 5mg OD Tab thyroxine 100µg OD ↑↑ Tab azaron (azathioprine) 150mg OD

7. S/B Registrar/ SP ↓ med 6 on 25/07/2016 Nasal twang - ++ , Opthalmoplegia GC – moderate Afebrile P – 90bpm HS – normal RS – clear P/A – soft Investigation Hb – 7.6gm/ dL TLC – 4000 cells/ mm3 Platelet – 298000/mm3 Treatment 1 point DNS Inj neostigmine 0.5mg BD Inj atropine 0.6mg before neostigmine ↑↑ Tab omnacortil (prednisolone) 40mg OD Tab thyroxine 100µg OD Tab azaron (azathioprine)150mg OD Tab distinon ( pyridostigmine ) 60mg BD Diagnosis - Myasthenia gravis with exacerbation

8. S/B Lecturer ↓ nephrology on 25/07/2016 Kindly send patient for plasmapheresis Right sided double lumen HD catheter inserted Advice HIV - negative HBsAg – negative B+ve Anti HCV Arrange 5 FFP Plasma filter Dialysis tubing

9. S/B Registrar ↓ med 6 on 26/07/2016 GC – moderate Afebrile P – 78 bpm BP – 110/70mm of Hg RS – NAD HS – Normal CNS – NAD Treatment 1 point DNS Inj neostigmine 0.5mg BD Inj atropine 0.6mg before neostigmine Tab omnacortil (prednisolone) 40mg OD Tab thyroxine 100µg OD Tab azaron (azathioprine) 150mg OD Tab distinon ( pyridostigmine ) 60mg BD

10. 26/07/2016 at 11am – Plasmapheresis - 1 ↓ All Aseptic Precautions double lumen Double Lumen Catheter inserted ↓ local anaesthesia procedure uneventful Patient had hypotension during Plasmapheresis 1.5 litre plasma removed 5 unit FFP + 1 litre NS infused Advice Inj monocef (ceftriaxone) 1 gm iv BD Arrange 5 unit of Fresh Frozen Plasma for next session on 28/07/2016 X ray chest PA view

11. S/B Reg ↓ med 6 / SP ↓ 6 on 27/07/2016 GC – moderate Afebrile P – 78 bpm BP – 110/70mm of Hg RS – NAD HS – Normal CNS – NAD Treatment 1 point DNS ↑↑ Inj neostigmine 0.5mg TDS Inj atropine 0.6mg before neostigmine Tab omnacortil 40mg OD Tab thyroxine 100µg OD Tab azaron 150mg OD Tab shelcal 500mg BD Tab distinon 60mg BD

12. S/B Lecturer ↓ Nephrology on 28/07/2016 - Plasmapheresis -2 Advice Plasmapheresis today 2 litre volume exchange 5 point FFP 2 point NS 1 point RL Inj calcium gluconate …post plasma pheresis Repeat CBC PT/INR Serum electrolyte

13. S/B Lecturer ↓ Nephrology 28/07/2016 at 3.45 pm While shifting patient c/o discomfort P – 150 bpm irregular SpO 2 – 94% Inj Lasix 20mg iv stat Inj hydrocortisone 100mg iv stat Drop in SpO2 to 70% Hence AMBU bag ventilation done SpO2 – 98 % achieved Bipap connected SpO2 – 98% maintained Semiconscious ?? Myasthenia Crisis Advice Shift to Intensive Cardiac Care Uunit & Continue bipap Urgent Ca ++, CBC , PT/INR, ABG

14. Transfer out notes to ICCU on 28/07/ 2016 C/O myasthenia gravis with exacerbation Treatment 1 point DNS Inj neostigmine 0.5mg TDS Inj atropine 0.6mg before neostigmine Tab omnacortil (prednisolone) 40mg OD Tab thyroxine 100µg OD Tab azaron (azathioprine) 150mg OD Inj monocef 1 gm BD Tab shelcal 500mg OD

15. Receiving notes in ICU 28/07/2016 P – 136bpm BP – 90/ 60 mm of Hg SpO2 – 100% Chest – clear Dyspnoeic Sr Ca ++ - 10.2 Sr Na+ - 142meq/L Sr K+ - 2.8 meq / L Sr Mg++ - 3.8 meq /L Treatment 2 point NS fast Inj neostigmine 0.5mg TDS Inj atropine 0.6mg before neostigmine Inj monocef 1gm iv BD Tab omnacortil 40mg OD Tab thyroxine 100µg OD Tab azaron 150mg OD Tab shelcal 500mg BD Tab distinon 60mg BD Inj KCl 40meq in 1 point NS over 8hrs

16. S/B Reg ↓ med 6 on 29/07/2016 at 8 AM GC – moderate Afebrile P – 86 bpm BP – 100/70 mm of Hg U/O – 800ml RS – NAD HS – Normal CNS – NAD P /A – soft Treatment Inj neostigmine 0.5mg TDS Inj atropine 0.6mg before neostigmine D 5 Tab omnacortil 40mg OD Tab thyroxine 100µg OD Tab azaron 150mg OD Tab shelcal 500mg BD Tab distinon 60mg BD D 3 Inj monocef 1gm iv BD pH – 7.4 HCO 3- - 22 P CO2 - 25

17. S/B Senior Physician ↓ 6 on 29/07/2016 at 10.40AM P – 90bpm Opthalmoplegia ++ No Cyanosis Chest – Clear Mild improvement in deglutition Treatment Inj neostigmine 0.5mg SOS ↑↑ Tab pyridostigmine 60mg TDS W/H omnacortil (prednisolone) D1/3 - Inj methyl prednisolone 500mg OD Rest ct all

18. Intubation notes 29/07/2016 ↓ All aseptic precautions patient was intubated with ET tube size 7.5 mm AE b/l equal fixed put on ventilatory support SpO2 - 92% Procedure - uneventful

19. S/B Registrar ↓ ICU 29/07/2016 at 6PM GC – poor Unconcious On ventilatory support HS – normal Chest – clear SpO2 – 92% Sr T 3 – 490 IU Sr T 4 – 18 IU TSH – 0.01IU Advice W/H Tab Thyroxine 100µg Rest ct all

20. S/B MO / Registrar /SP ↓ ICCU at 30/07/2016 at 8 AM GC – moderate Afebrile P – 86 bpm Chest – clear BP – 110/70mm of Hg U/O – 650ml RS – NAD HS – Normal CNS – NAD P/A – soft non tender Treatment D 1 Inj levofloxacin 500mg OD D 4 Inj monocef 1gm iv BD D 2/3 Inj methyl prednisolone 500mg OD Tab azaron (azathioprine)150mg OD Inj neostigmine 0.5mg TDS Inj atropine 0.6mg before neostigmine Tab pyridostigmine 60mg OD Tab shelcal 500mg BD

21. S/B Lecturer nephrology at 30/07/2016 c/o myasthenia gravis in myasthenic crisis Intubated yesterday in view of poor respiratory efforts P – 80 bpm BP - 110/70 mm of Hg B/L AEBE Concious oriented / moves limb on command Advice Plasmapheresis today Arrange 5 @ FFP Send patient with accompanying resident doctors by12.30PM High risk plasmapheresis explained to relatives Sr Ca + -9.8mg/ dL Sr Mg+ -1.97mg/ dL Sr Na+ -137mEq/L Sr K+ - 2.6mEq/L

22. S/B SP ↓ 6 at 30/07/2016 at 2 PM GC- not stable on ventilator Conscious afebrile P – 78 bpm B/L Clear HS – normal Treatment ↑↑ Tab pyridostigmine 60 mg QID Rest ct all Investigation Sr urea -14mg/ dL Sr creat – 0.7mg/ dL T protein – 5.3gm% T Bilirubin – 0.7mg% ALP - 44 IU/L SGOT – 40 IU/L SGPT – 13 IU/L

23. S/B Lecturer ↓ Nephrology on 30/07/2016 - Plasmapheresis - 3 c/o myasthenia gravis currently in crisis on ventilatory support plasmapheresis 3 rd today No spontaneous breathing on Intermittent Positive Pressure Ventilation Advice 2 litre exchange 5 FFP 2 @ RL 1 @ NS Inj calcium gluconate 10 cc post plasmapheresis Post plasmapheresis – there was spontaneous trigerring on ventilator Advice PT/INR , Sr electrolytes Tensilon ( edrophonium challenge test) Plan for IVIg Would offer plasamapheresis on Monday with 5@ FFP & accompanying medicine resident @ 10 AM

24. S/B Registrar ↓ ICCU / SP ↓ 2 on 31/07/2016 at 8 AM Patient on ventilator GC – moderate Afebrile P – 82 bpm BP – 120/80 mm of Hg U/O – 1200ml RS – clear P/A – soft non tender CVS – S 1 S 2 CNS – conscious oriented Treatment D 2 inj levofloxacin 500mg OD D 5 inj monocef 1gm BD D 3/3 inj methylprednisolone 500mg OD Tab azoran 150mg OD Inj pyridostigmine 60 mg QID Inj neostigmine 0.5mg im SOS Inj atropine 0.6mg SOS before inj neostigmine Tab shelcal 1 BD PT/INR - 13/1.11

25. S/B registrar ↓ ICCU / SP ↓ 6 on 1/08/2016 at 8 AM GC – not stable Afebrile P – 80 bpm BP – 130/90 mm of Hg U/O – 5 00ml RS – clear P/A – soft non tender CVS – S 1 S 2 CNS – NAD SpO2 – 100% Treatment ↓↓ Inj pyridostigmine 60 mg TDS D 3 inj levofloxacin 500mg OD D 6 inj monocef 1gm BD Inj neostigmine 0.5mg im SOS Inj atropine 2cc BD Tab shelcal 1 BD Tab azoran 150mg OD

26. Transfer notes 11PM at 01/08/2016 Here by transferring out this patient from ward 24 to nephrology for plasmapheresis c/o myasthenia gravis with crisis Treatment Inj pyridostigmine 60 mg TDS Inj neostigmine 0.5mg im SOS Inj atropine 0.6mg SOS before inj neostigmine D 3 inj levofloxacin 500mg OD D 6 inj monocef 1gm BD Tab azoran 150mg OD

27. S/B Lecturer ↓ Nephrology on 01/08/2016 Plasmapheresis - 4 c/o myasthenia gravis with crisis BP – 120/ 80 mm of Hg Advice Plasmapheresis today 2 litre volume exchange 5 point FFP 2 point NS 2 point RL Inj calcium gluconate …post plasma pheresis

28. S/B Registrar ↓ ICCU / SP ↓ 2 on 02/08/2016 at 8 AM GC – not stable Afebrile P – 86 bpm BP – 120/80 mm of Hg U/O – 2000ml SpO2 – 99% RS – clear CVS – S 1 S 2 CNS – conscious oriented Proximal muscle weakness + Opthalmoplegia + Treatment Inj pyridostigmine 60 mg TDS Inj neostigmine 0.5mg im SOS Inj atropine 0.6mg SOS before inj neostigmine Inj rantac 50mg BD D 4 inj levofloxacin 500mg OD D 7 inj monocef 1gm BD Tab shelcal 1 BD Tab azoran 150mg OD

29. S/B SP ↓ 6/ SP ICCU at 02/08/2016 at 10 AM GC – moderate Conscious Afebrile P – 80bpm Wt – 48 × 2 = 96gm Advice Plasmapheresis Free T3 , T4 , TSH Endocrinologist call CVTS call Treatment Ct all Inj IVIg 20gm/day × 5 days -last day 15gm

30. 03/08/2016 To CVTS surgeon, Sir /madam , kindly evaluate this patient c/o hypothyroidism with myasthenia gravis with thymoma patient is not improving on plasmapheresis . Kindly advice regarding thymectomy Thanking you S/B by Dr Ashish Advice Thymectomy only after GC – improves

31. S/B registrar ↓ ICCU / SP ↓ 6 on 03/08/2016 at 8 AM Patient on ventilator GC – not stable Ventilatory support Afebrile P – 90 bpm BP – 110/70 mm of Hg RS – clear P/A – soft non tender CVS – S 1 S 2 CNS – conscious orient ed Treatment Inj pyridostigmine 60 mg TDS Inj neostigmine 0.5mg im SOS Inj atropine 0.6mg SOS before inj neostigmine D 4 inj levofloxacin 500mg OD D 9 inj monocef 1gm BD Tab shelcal 1 BD Tab azoran 150mg OD Plasmapheresis Nephrologist reference

32. S/B Lecturer ↓ nephrology – 03/08/2016 Plasmapheresis – 5 C/O myasthenia gravis with crisis received 4 plasmapheresis Advice Send patient accompanying medicine resident with 5 @ Fresh Frozen Plasma Plasma removal – 2 L Replace with 5 Fresh Frozen Plasma 2 @ RL

33. S/B Registrar ↓ ICCU / SP ↓ 6 on 04/08/2016 at 8 AM GC – not stable Afebrile P – 82 bpm BP – 120/90 mm of Hg SpO2 – 100% on Ventilatory support U/O – 1600ml RS – clear P/A – soft non tender CVS – S 1 S 2 CNS – conscious oriented Treatment Inj pyridostigmine 60 mg TDS Inj neostigmine 0.5mg im SOS Inj atropine 0.6mg SOS before inj neostigmine D 5 inj levofloxacin 500mg OD D 10 inj monocef 1gm BD Tab shelcal 1 BD Tab azoran 150mg OD Plasmapheresis

34. 04/08/2016 Recovery Room To MO/ Registrar Anaesthesia on call kindly call over to evaluate this patient a c/o myasthenia gravis on ventilation not maintaining saturation on A/C mode and opine expertise management Thanking you

35. S/B Anaesthetist on 04/08/2016 C/O myasthenia gravis Conscious oriented Afebrile P – 83 bpm BP – 120/70 mm of Hg RS – clear CVS – S 1 S 2 SpO2- 96% Ventilation Mode – NC/AC RR - 16 cycles/min Positive End Expiratory Pressure - 5 TN – 360 FiO2 -100% Advice Propped up Ct ventilatory support Ct all

36. S/B Registrar ↓ ICCU / SP ↓ 6 on 04/08/2016 at 8 AM GC – not stable Afebrile P – 95 bpm BP – 130/70 mm of Hg SpO2 – 100% on Ventilatory support U/O – 1300ml RS – clear P/A – soft non tender CVS – S 1 S 2 CNS – conscious oriented Treatment Inj pyridostigmine 6 0 mg TDS Inj neostigmine 0.5mg im SOS Inj atropine 0.5cc before inj neostigmine D 6 inj levofloxacin 500mg OD D 11 inj monocef 1gm BD Tab shelcal 1 BD Tab azoran 150mg OD Tracheostomy tommorrow

37. 04/08/2016 at 1 AM To , Medical officer / registrar Anaesthesia on call, kindly call over to evaluate this patient a c/o myasthenia gravis on ventilation not maintaining saturation on A/C mode and opine expertise management thanks

38. 04/08/2016 at 1.05 AM S/B Anaesthesiologist Registrar A case of myasthenia gravis Ventilation Mode VC/AC Rate – 16 cpm PEEP – 5 T n – 360 FiO 2 – 100% O/E Conscious oriented Afebrile P – 83 bpm BP – 120/70 mm of Hg CVS - NAD SpO2 – 96% Advice Propped up Ct all

39. Treatment on 05/08/2016 , 06/08/2016 , 07/08/2016 08/08/2016 , same as on 04/08/2016 ENT reference was done on 06/08/2016 and tracheostomy was done on 06/08/2016 under LA and under all aseptic precautions RT feeding was started on 08/08/2016 and diet reference was done on same day

40. S/B Registrar ↓ ICCU / SP ↓ 6 on 09/08/2016 at 8 AM GC – moderate Afebrile P – 95 bpm BP – 130/70 mm of Hg SpO2 – 100% on Ventilatory support U/O – 1000ml RS – clear P/A – soft non tender CVS – S 1 S 2 CNS – conscious oriented Treatment D 1 Inj piptaz 4.5 gm TDS Inj pyridostigmine 80 mg QID D 10 inj levofloxacin 500mg OD Inj neostigmine 0.5mg im SOS Inj atropine 0.6cc before inj neostigmine D 11 inj monocef 1gm BD Tab shelcal 1 BD Tab azoran 150mg OD IVF – 2 point NS Inj pantop 40mg OD Inj emset 4 mg TDS

41. 09/08/2016 AT 9.30 AM S/B Senior Physician ↓ 6 GC – moderate Afebrile P – 90 bpm Chest – clear Tracheostomy tube in situ P/A – soft Treatment Inj Amino drip OD Protein powder Inj wymesone (dexamethasone) 4 mg 8hrly Tab Azoran 150mg OD D 2 Inj piptaz 4.5 gm TDS D 10 Inj levofloxacin 500mg OD Tab pyridostigmine 60mg TDS Inj emset 4 mg TDS

42. 10/08/2016 to 18/08/2016 Treatment was same as on 09/08/2016 Except 12/08/2016 tracheal culture & sensitivity pseudomonas grown R – amikacin , aztreonam , cefepime , ceftazidime , gentamicin , imipenem , piperacillin S – polymyxin B Day 17 Inj Levofloxacin was stopped on 16/08/2016 17/08/2016 bladder clamping and bladder wash started tracheostomy dressing changed

43. S/B Neurologist on 18/08/2016 25yrs /F Patient diagnosed case of myasthenia gravis { AChR antibody - + ve } h/o diplopia / weakness of all 4 limbs since 1year O/E Pt intubated on mechanical ventilation SIMV mode with SpO2- 96% Occular movements are normal Neck weakness - + Power – grade 4 in all 4 limbs DTR – 2+ Plantar – b/l ↓ Pt received plasmapheresis 5 cycles Received IVIg 5 days (2gm/kg) Patient improving according history Advice Ct tab pyridostigmine 60mg TDS Ct tab dexamethasone 4mg TDS Ct tab azoran 150mg OD Can be considered for repeat IVIg after 1month if relapse occurs or difficulty to wean situation

44. S/B Registrar ↓ ICCU / SP ↓ 6 on 19/08/2016 at 8 AM GC – moderate Afebrile P – 80 bpm BP – 130/80 mm of Hg SpO2 – 98% on Ventilatory support U/O – 8 00ml RS – clear P/A – soft non tender CVS – S 1 S 2 CNS – conscious oriented Treatment Amino drip alternate day D 11 Inj piptaz 4.5 gm TDS Inj wymesone 4mg TDS Inj atropine 0.6cc BD Tab pyridostigmine 60 mg TDS Tab azoran 150mg OD Inj pantop 40mg OD

45. 20/08/2016 same as on 19/08/2016 21/08/2016 same as on 20/08/2016 22/08/2016 , 23/08/2016 same as on 21/08/2016 Augmentin was started and piptaz was stopped on 20/08/2016 Nebulisation with mucomix was added on 21/08/2016

46. Patient was discharged on 16/09/2016 on following medicines Tab levofloxacin 0.5gm BD Tab predmet 16 mg TDS Tab distinus ( pyridostigmine ) 60mg TDS Tab azoran 150mg BD Protein biscuits Follow up after 15 days for work up of thymectomy

47. Case Discussion

48. Myasthenia Gravis Neuromuscular disorder characterized by weakness and fatigability of skeletal muscles Underlying defect - ↓ in number of available acetylcholine receptors ( AChRs ) at neuromuscular junctions due to an antibody-mediated autoimmune attack Myasthenic crisis - Severe weakness of bulbar (innervated by cranial nerves) and/or Respiratory muscles, enough to cause inability to maintain adequate ventilation and/or permeability of upper airways, causing respiratory failure that requires artificial airway or ventilator support

49. Standard treatment

50. Rationality Anticholinesterase medication Inj neostigmine 0.5mg BD Tab / Inj pyridostigmine 60 mg TDS Use – rational Improve muscle contraction - Ach released from prejunctional endings to accumulate and act on receptors over a larger area, as well as by directly depolarizing endplate Whether combination can be used is not given in any text book

51. Rationality Anticholinergic drugs Inj atropine 0.6mg before neostigmine Use – rational To avoid muscarinic side effects of anticholinesterase drug

52. Corticosteroids / Immunosuppresion Inj methyl prednisolone 15- 25mg /day in single dose to avoid side effects Use – Rational Inhibit production of Nicotinic Receptor (NR)-antibodies & may ↑ synthesis of NRs Dose ↑ stepwise - by 5 mg/d at 2- to 3-day intervals → marked Clinical improvement or dose of 50 - 60 mg/d reached This dose maintained for 1 - 3months Alternate-day regimen over course of 1 -3 months Goal is to ↓ dose on off day to zero or to minimal level

53. Rationality Tab azathioprine 50mg OD Use – Rational Previously most commonly used immunosuppressive agent because of its Relative safety Long track record Therapeutic effect may add to glucocorticoids effect &/or allow glucocorticoid dose to ↓

54. Rationality Plasmapheresis Use – rational Plasma contains pathogenic antibodies, is mechanically separated from blood cells Course of 5 exchanges ( 3 - 4 L per exchange) - Over 10 to 14 day period Advantages in Our set up – Comparatively inexpensive to IVIg but requires expertise

55. Rationality Intravenous immunoglobulins Use – rational Advantage Doesn’t require special equipment & Large-bore venous access Ease of administration Disadvantage – expensive Usual dose is 2 g/kg - over 5 days (400 mg/kg per day )

56. Rationality Antibiotics Inj ceftriaxone 1gm iv BD Inj levofloxacin 0.5gm iv BD Inj piperacillin tazobactum 4.5 gm TDS Cap amoxicillin clavulunate 625mg BD Use – rational Most common cause of crisis is intercurrent infection

57. Rationality Tab thyroxine 100µg OD Use – rational Hypothyroidism Inj KCl 10-20meq/ hr Use – rational To treat hypokalemia Inj calcium gluconate 90mg iv over 10 min post plasma pheresis Use – rational To treat hypocalcemia associated with plasmapheresis

58. Not rational Prednisolone dose on admission should have been increased Brand names were used Respiratory secretions – culture and sensitivity was done late Instead of ceftriaxone they could have used ceftazidime and cefoperazone

59. Not rational Culture and sensitivity of drugs given was not done Urine & blood culture & sensitivity was not done At some places doses and route of administration were missing

60. Next – CCD – DR Swarnank Parmar

61. Management of myasthenic crisis exacerbation of weakness sufficient to endanger life (usually consists of respiratory failure caused by diaphragmatic & intercostal muscle weakness) Crisis rarely occurs in properly managed patients Intensive care units staffed with teams experienced in the management of MG, respiratory insufficiency, infectious disease , fluid & electrolyte therapy Deterioration could be due to excessive anticholinesterase medication ( c holinergic crisis) - best excluded by temporarily stopping anticholinesterase drugs

62. most common cause of crisis is intercurrent infection This should be treated immediately, because the mechanical and immu-nologic defenses of the patient can be assumed to be compromised. The myasthenic patient with fever & early infection should be treated like other immunocompromised patients. Early & effective antibiotic therapy, respiratory assistance (preferably noninvasive , using bilevel positive airway pressure), & pulmonary physiotherapy are essentials of the treatment program As discussed above plasmapheresis or IVIg is frequently helpful in hastening recovery

63. National Treatment Guidelines for Antimicrobial Use in Infectious Diseases - 2016