THE CASE OF MP

Jara-Medrano22.July.2010

GENERAL DATA

• MP• 70-year-old male• Car technician

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.

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

PHYSICAL EXAMINATION

• Awake, with occasional coughs.• Vital Signs

– Pulse rate: 108 beats/min– Respiratory rate: 30 breaths/min– Temperature: 38oC– Blood pressure: 100/60

DIAGNOSTICS

• Chest radiograph (CXR)– Right lower lobe consolidation– Minimal pleural effusion

• Complete Blood Count (CBC)– Results not yet available

PRIMARY IMPRESSION

• Sepsis secondary to moderate-risk community acquired pneumonia (MR-CAP)

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 > 38oC) or hypothermia– Tachypnea (RR>24 breaths/min)– Tachycardia (HR>90 beats/min)– Leukocytosis or leukopenia

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

STEP 1. THE PATIENT’S PROBLEMS

• Sepsis secondary to MR-CAP.• Uncontrolled blood sugar due to poorly

maintained diabetes.

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

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

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

Efficacy Safety Suitability

Penicilline.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

Efficacy Safety Suitability

Cephalosporine.g. Cefuroxime

Pharmacodynamics:- Active against community acquired E.coli, Klebsiella, Proteus, H. influenzae, Enterobacteriaceae, Serratia, Neisseria gonorrhea, Pseudomonas aeruginosaPharmacokinetics: -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.

Efficacy Safety Suitability

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

Efficacy Safety Suitability

Extended MacrolidesEx. Azithromycin

Pharmacodynamics:-Resp tract infections; Skin and soft tissue infections ; Uncomplicated genital chlamydial infections ; Uncomplicated gonorrhoea ;. Prophylaxis of disseminated MAC infectionsPharmacokinetics: -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.

Efficacy Safety Suitability

Respiratory Fluoroquinolonese.g. LevofloxacinPharmacodynamics:-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 CAPPharmacokinetics: -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

Drug Efficacy Safety Suitability

Penicillin e.g. Co-amoxiclav

++++ ++++ -

Cephalosprin 2nd and 3rd generation

++++ ++++ -

Cabapenem ++++ +++ -

IV Extended Macrolidee.g. Azithromycin

++++ ++++ +

IV Fluoroquinolone e.g. Levofloxacin

+++ ++++ ++++

Cost per day Total Cost of Treatment

Penicillin e.g. Co-amoxiclav

2,400 + 1,800 44,800 - 88,200

Cephalosprin 2nd and 3rd generation

1,800 + 1,800 50,400 - 75, 600

Carbapenem 2,000-5,000 + 1,800

28,000-70,000+25200

Extended Macrolidee.g. Azithromycin

300 4200-6400

IV Fluoroquinolone e.g. Levofloxacin

1,400-2,800 19,600-58,800

STEP 3. VERIFY P-DRUG

Decision to chose Fluoroquinolone over anExtended 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.

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.

STEP 3. VERIFY P-DRUGDosage• 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

STEP 4. WRITE A PRESCRIPTION/ START TREATMENT

Insert CJ’s file

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

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

STEP 5. GIVE INFORMATION, INSTRUCTIONS AND WARNINGS

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

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.

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

Indications for streamlining of antibiotic therapy:

1. Resolution of fever for > 24 hours2. Less cough and resolution of respiratory distress (normalization of respiratoryrate)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 bacilli5. No unstable comorbid condition or life-threatening complication such asmyocardial infarction, congestive heart failure, complete heart block, new atrialfi brillation, supraventricular tachycardia, etc.6. No sign of organ dysfunction such as hypotension, acute mental changes, BUNto creatinine ratio of >10:1, hypoxemia, and metabolic acidosis7. Patient is clinically hydrated, taking oral fl uids and is able to take oralmedications

Switch therapy from Parenteral Antibiotics

The choice of oral antibiotics following initialparenteral therapy is based on available cultureresults, antimicrobial spectrum, effi cacy, safetyand cost. In general, when switching to oralantibiotics, either the same agent as the parenteral antibiotic or an antibiotic from thesame drug class should be used.

Criteria for Discharge

• During the 24 hours before discharge, the patient should have the following characteristics:

1. temperature of 36-37.5o C2. pulse < 100/min3. respiratory rate between 16-24/minute4. systolic BP >90 mmHg5. blood oxygen saturation >90%6. functioning gastrointestinal tract