1. THE CASE OF MP Jara-Medrano 22.July.2010

2. GENERAL DATA MP 70-year-old male Car technician

3. HISTORY OF PRESENT ILLNESS 3 days PTC MP experienced fever, generalized body weakness, productive cough and difficulty breathing. Self-medicated with salbutamol.No relief of symptoms, prompted consult.

4. PAST MEDICAL HISTORY Known diabetic since 5 years ago – Maintained on Metformin with poor compliance (+) Adverse drug reactions/rashes – Amoxicillin – Penicillin – Cefuroxime (–) Hypertension (–) Travel history for the past 6 months

5. PHYSICAL EXAMINATION Awake, with occasional coughs. Vital Signs – Pulse rate: 108 beats/min – Respiratory rate: 30 breaths/min – Temperature: 38 o C – Blood pressure: 100/60

6. DIAGNOSTICS Chest radiograph (CXR) – Right lower lobe consolidation – Minimal pleural effusion Complete Blood Count (CBC) – Results not yet available

7. PRIMARY IMPRESSION Sepsis secondary to moderate-risk community acquired pneumonia (MR-CAP)

8. DIAGNOSIS of SEPSIS Sepsis – Systemic inflammatory response syndrome (SIRS) – AND proven or suspected microbial etiology SIRS (2 or more of the following conditions) – Fever (oral temperature > 38 o C) or hypothermia – Tachypnea (RR>24 breaths/min) – Tachycardia (HR>90 beats/min) – Leukocytosis or leukopenia

9. DIAGNOSIS of MR-CAP Any of the following (Philippine CPG, 2010): – Unstable vital signs Tachypnea, tachycardia, fever/hypothermia, SBP < 90 mmHg and DBP ≤ 60mmHg. – Altered mental status of acute onset – Suspected aspiration – Decompensated co-morbid condition – Chest X-ray Multilobar infiltrates Pleural effusion or abscess

10. STEP 1. THE PATIENT’S PROBLEMS Sepsis secondary to MR-CAP. Uncontrolled blood sugar due to poorly maintained diabetes.

11. STEP 2. THERAPEUTIC OBJECTIVES to stabilize the patient to treat the focus of infection to provide symptomatic relief to prevent disease progression and possible complications to address the patient’s co-morbid condition (diabetes) to prevent development of antibiotic resistance to prevent disease recurrence to observe probable occurrence of adverse drug reactions

12. STEP 3. VERIFY P-DRUG The 2010 CPG on CAP recommends the use of the following for MR-CAP: IV non-antipseudomonal β-lactam (BLIC, cephalosporin or carbapenem) + an extended macrolide OR IV non-antipseudomonal β-lactam + fluoroquinolone

13. STEP 3. VERIFY P-DRUG Patient’s hypersensitivity to β-lactam antibiotics, however compels us to choose monotherapy using a respiratory fluoroquinolone such as levofloxacin or moxifloxacin

14. EfficacySafetySuitability Penicillin e.g. Co-amoxiclav Pharmacodynamics: -active against most strep, pneumococci, meninggococci, oral anaerobes, spirochetes, listeria, Corynebacterium spp. Clavunalic acid extends activity to gram negatives such as H.influenzae and E. coli. Pharmacokinetics: -half-life: 1 hr in adults, well absorbed orally. Nausea, vomiting, diarrhoea, indigestion, rash and urticaria, candida superinfection. Potentially Fatal: Anaphylactic reaction with CV collapse esp with parenteral use. Contraindicated in hypersensitive patients

15. EfficacySafetySuitability Cephalosporin e.g. Cefuroxime Pharmacodynamics: - Active against community acquired E.coli, Klebsiella, Proteus, H. influenzae, Enterobacteriaceae, Serratia, Neisseria gonorrhea, Pseudomonas aeruginosa Pharmacokinetics: -half-life: 45 min, 89% metabolized in kidneys, high concn in urine. Distributed in pleural and joint fluids, bile, sputum, bone, aqueous humor, and in CSF if meninges are inflammed. Thrombophlebitis. Pruritus, urticaria, +ve Coombs' test, diarrhea, nausea, pseudomembranous colitis. Decrease in Hb & hematocrit, transient increase in liver enzymes, elevation in serum creatinine & BUN. Possibly seizure & angioedema. Hypersensitivity to penicillins. Possible superinfection in prolonged use. Nephrotoxicity & ototoxicity.

16. EfficacySafetySuitability Carbapenem Pharmacodynamics: -Lower resp tract, UTI including complicated, intra-abdominal, gynecological including postpartum, skin & skin structure infections. Septicemia, meningitis. Pharmacokinetics: Good oral absorption & distributes widely throughout the body, except to the brain and CSF. Should not be administered with food.extensive tissue distribution and high drug concentrations within cells. Major excretion:bile, minor in liver. Thrombocythemia. Nausea, vomiting, diarrhea. Increases in serum transaminases, bilirubin, alkaline phosphatase, lactic dehydrogenase. Inflammation, thrombophlebitis, pain Hypersensitivity. Infants <3 mos. Pregnancy & lactation

17. EfficacySafetySuitability Extended Macrolides Ex. Azithromycin Pharmacodynamics: -Resp tract infections; Skin and soft tissue infections ; Uncomplicated genital chlamydial infections ; Uncomplicated gonorrhoea ;. Prophylaxis of disseminated MAC infections Pharmacokinetics: -absorbed rapidly thru oral route; extensive tissue distribution w/n cells; minor hepatic metabolism but primarily metabolized in kidneys, Mild to moderate nausea, vomiting, abdominal pain, dyspepsia, flatulence, diarrhoea, cramping; angioedema, cholestatic jaundice; dizziness, headache, vertigo, somnolence; transient elevations of liver enzyme values Hypersensitivity.

18. EfficacySafetySuitability Respiratory Fluoroquinolones e.g. Levofloxacin Pharmacodynamics: -urinary and GI infections, non- gonococcal urethritis, severe infections due to gram - infections, combination treatment of MDR TB, prophylaxis for meningococcal infections and antrax infeactions and CAP Pharmacokinetics: -absorbed well in oral preparations, good distribution, half-life of 1-3 hrs; renal clearance mild nausea, vomiting, diarrhea,hallucinations, delirium, and seizures, hypoglycemia, Rashes, including photosensitivity reactions Good for patient but might interfere with glycemic control

20. Cost per dayTotal Cost of Treatment Penicillin e.g. Co-amoxiclav 2,400 + 1,80044,800 - 88,200 Cephalosprin 2 nd and 3 rd generation 1,800 + 1,80050,400 - 75, 600 Carbapenem 2,000-5,000 + 1,800 28,000-70,000+ 25200 Extended Macrolide e.g. Azithromycin 3004200-6400 IV Fluoroquinolone e.g. Levofloxacin 1,400-2,80019,600-58,800

21. STEP 3. VERIFY P-DRUG Decision to chose Fluoroquinolone over an Extended Macrolide A respiratory fluoroquinolone as monotherapy was chosen over an extended macrolide due to the severity of the patient's situation. Presence of sepsis and concomittant uncontrolled diabetes in the patient compels us to choose a respiratory fluoroquinolone due to its stronger activity against the suspected pathogens.

22. STEP 3. VERIFY P-DRUG Decision to choose Levofloxacin over Moxifloxacin Though Levofloxacin and Moxifloxacin shows equal efficacy in the treatment of CAP-MR, Levofloxacin is chosen due to its more affordable price.

23. STEP 3. VERIFY P-DRUG Dosage Patient should be started with 750mg IV Levothyroxine q24 hour. Assessment should be done after 3days so that parenteral therapy can be descalated to oral therapy once patient starts improving. Nonresponse to therapy is an indication to examine Culture-Sensitivity of the etiologic agent and proper adminstration of adequate antimicrobial

24. STEP 4. WRITE A PRESCRIPTION/ START TREATMENT Insert CJ’s file

25. STEP 5. GIVE INFORMATION, INSTRUCTIONS AND WARNINGS Effects of the Drugs Levofloxacin is for the empiric treatment to cover potential pathogens of CAP-MR to eliminate infection Expected symptoms to disappear: fever, generalized body weakness, productive cough and difficulty breathing Most patients with uncomplicated bacterial pneumonia will respond to treatment within 24 to 72 hours Antibiotics taken incorrectly or not at all may worsen the disease and may contribute to the development of antibiotic resistance

26. Side Effects Levofloxacin is generally well tolerated Mild nausea, vomiting, and/or abdominal discomfort CNS side effects, predominately mild headache and dizziness STEP 5. GIVE INFORMATION, INSTRUCTIONS AND WARNINGS

27. Instructions & Warnings Temperature, RR, HR, BP, sensorium, O2 saturation and inspired oxygen concentration should be monitored to assess response to therapy. A patient is considered to have responded to treatment if fever decreases within 72 hr, temperature normalizes within 5 days and respiratory signs, particularly tachypnea, return to normal

28. STEP 5. GIVE INFORMATION, INSTRUCTIONS AND WARNINGS Instructions & Warnings The patient should be afebrile for 48 to 72 hr with no signs of clinical instability before discontinuation of treatment Patients who are not improving after 72 hr of empiric antibiotic therapy, the history, physical examination and the results of all available investigations should be reviewed.

29. STEP 6. MONITOR Duration of treatment for moderate-risk CAP: 14-21 days Assess initial therapy by monitoring: – Temperature – respiratory rate – heart rate – blood pressure – sensorium – oxygen saturation – inspired oxygen concentration

30. Indications for streamlining of antibiotic therapy: 1. Resolution of fever for > 24 hours 2. Less cough and resolution of respiratory distress (normalization of respiratory rate) 3. Improving white blood cell count, no bacteremia. 4. Etiologic agent is not a high-risk (virulent/resistant) pathogen e.g. Legionella, S. aureus or Gram- negative enteric bacilli 5. No unstable comorbid condition or life-threatening complication such as myocardial infarction, congestive heart failure, complete heart block, new atrial fi brillation, supraventricular tachycardia, etc. 6. No sign of organ dysfunction such as hypotension, acute mental changes, BUN to creatinine ratio of >10:1, hypoxemia, and metabolic acidosis 7. Patient is clinically hydrated, taking oral fl uids and is able to take oral medications

31. Switch therapy from Parenteral Antibiotics The choice of oral antibiotics following initial parenteral therapy is based on available culture results, antimicrobial spectrum, effi cacy, safety and cost. In general, when switching to oral antibiotics, either the same agent as the parenteral antibiotic or an antibiotic from the same drug class should be used.

32. Criteria for Discharge During the 24 hours before discharge, the patient should have the following characteristics: 1. temperature of 36-37.5o C 2. pulse < 100/min 3. respiratory rate between 16-24/minute 4. systolic BP >90 mmHg 5. blood oxygen saturation >90% 6. functioning gastrointestinal tract