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

Patient’s hypersensitivity to β-lactam antibiotics, however compels us to choose monotherapy using a respiratory fluoroquinolone such as levofloxacin or moxifloxacin

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

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.

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

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.

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

DrugEfficacySafetySuitability Penicillin e.g. Co-amoxiclav Cephalosprin 2 nd and 3 rd generation Cabapenem IV Extended Macrolide e.g. Azithromycin IV Fluoroquinolone e.g. Levofloxacin

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

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.

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.

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