antibiotics basics for clinicians
TRANSCRIPT
Dr. Lokesh Garg
M.B.B.S. M.D.
One of the most commonly used group of drugs.
A medical doctor has to know the definite clinical pharmacology of antibiotics, how to select & use them rationally.
- Avoid adverse effects on the patient
- Avoid emergence of antibiotic resistance
- Avoid unnecessary increases in the cost of health care
Definition
Antibiotics are substances that kill or inhibit the growth
of micro-organisms.
Bacteriostatic
Bactericidal
Based on their mechanism of action, antibiotics can be divided into the following classes:
Inhibitors of Cell Wall synthesis Inhibitors of Protein synthesis Inhibitors of Nucleic Acid synthesis
This class includes:
Penicillin Cephalosporin Carbapenems Monobactams Vancomycin Beta lactamase inhibitors
B – lactam antibiotics
Category Parenteral Agents Oral Agents
Natural Penicillins Penicillin G Penicillin V
Antistaphylococcal penicillins
Nafcillin, oxacillin Dicloxacillin
Aminopenicillins Ampicillin Amoxicillin and Ampicillin
Aminopenicillin + -lactamase inhibitor
Ampicillin-sulbactam Amoxicillin-clavulanate
Extended-spectrum penicillin
Piperacillin, ticaricillin Carbenicillin
Extended-spectrum penicillin + -lactamase inhibitor
Piperacillin-tazobactam, ticaricillin-clavulanate
THE PENICILLINS
Class Examples Routes of administration
First generation
Cephalexin/cefadroxilCefazolin
Orali.v.
Second generation
CefuroximeCefoxitin
Oral/ i.v.
Third generation
CefiximeCeftriaxone/cefotaxim
Ceftazidime
Orali.v.i.v.
Fourth generation
Cefipime i.v.
Adverse Effects
Allergic reactions: itch, rash, fever, angioedema, rarely anaphylactic reaction
GI upset and diarrhoea
Interstitial nephritis and increased renal damage in combination with aminoglycosides
Pharmacokinetics
Bactericidal
Safe in pregnancy
Dosage needs to be reduced in cases of impaired renal function.
This class includes:- Macrolides- erythromycin, clarithromycin,
azithromycin
Lincosamides- clindamycin
Aminoglycosides- gentamicin, tobramycin, amikacin, netilmicin,neomycin, streptomycin.
Tetracyclines- tetracycline, doxycycline,minocycline
Chloramphenicol
Pharmacokinetics:
Bacteriostatic
Dose adjustment in renal failure is not necessary
Adverse Effects :
GI upset
Cholestatic jaundice
Prolongation of QT interval (erythromycin)
Theophylline, oral anticoagulants cannot be administered simultaneously
PharmacokineticsPharmacokinetics
Bectericidal
Negligible oral absorption
Dose adjustment is critical in renal impairment
Adverse Effects Ototoxic (permanent)
Avoid concurrent use of other ototoxics drugs for eg. Lasix , minocycline
Nephrotoxic ( reversible): use cautiously with other nephrotoxic drugs
Pharmacokinetics
Bacteriostatic
Best oral absorption in fasting state
Adverse Effects
Contraindicated in renal failure (except doxycycline and minocycline)
Nausea, diarrhoea
Binds to metallic ions in bones and teeth (to be avoided in children and
in pregnancy)
Phototoxic skin reactions
This group includesThis group includes::
Sulphonamides: Sulfamethoxazole, sulfadoxine
Trimethoprim
Quinolones: Ciprofloxacin, levofloxacin, pefloxacin, ofloxacin, norfloxacin, gatifloxacin, moxifloxacin, sparfloxacin
Rifampicin
Azoles: This group includes-
Antibacterial- Metronidazole, secnidazole, tinidazole,
Antihelminth- Albendazole, Mebendazole, thiabendazole
Pharmacokinetics
Bactericidal
Well absorbed orally with good bioavailability
Dose reduction necessary in renal failure
Adverse Effects
Fatal marrow dysplasia and haemolysis in G6PD deficiency
Skin and mucocutaneous reactions: Stevens- Johnson syndrome
Contraindicated in pregnancy
Pharmacokinetics
Bectericidal
Well absorbed after oral administration
Dose adjustment required in renal impairment (except moxifloxacin and trovafloxacin)
These two drugs are contraindicated in hepatic failure
Adverse Effects
GI side effects
CNS effects such as restlessness, headache, insomnia, confusion and seizures in the elderly
Rare skin reactions
Should be avoided in pregnancy
Not routinely recommended for use in patients under 18 years
of age
Pharmacokinetics
Almost completely absorbed after oral administration (60% after rectal administration).
Adverse Effects
Metallic taste
Severe vomiting if taken with alcohol (disulfiram like syndrome )
CNS: Meningitis, brain abscess etc
Respiratory: URTI, Pneumonia, Lung abscess, Bronchiectasis
CVS: Acute rheumatic fever, Infective endocarditis
GIT and HBS: Cholera, Bacillary dysentery, Enteric fever, gastroenteritis, peritonitis,liver abscess
Genitourinary: UTI, pyelonephritis, STDs
Skin : Cellulitis necrotizing fascitis
Musculoskeletal: Osteomyelitis, Septic arthritis
Mycobacterial Infections: Tuberculosis, Leprosy
Chlamydial Infections
Systemic Infections: Sepsis syndrome
62 year old male presents to your clinic with c/o: Cough with expectoration x 4days
◦ Intermittent fever, measured to 100.8◦ Chest pain – Rt side
PMHx
◦ Healthyo No H/O hospitalization in recent pasto not on any medication
Drink socially , non smoker
Exam
VS – temp 100.3, P 92, RR 18, Spo2 - 96% on room air, BP 123/75
HEENT – normal
Neck – normal w/o palpable LN or TMG
Lungs – Bronchial breath sound in I/S , I/A on Rt side, clear at bases,
CV – normal
Legs – no edema
Case 1
Community –acquired Pneumonia (CAP)
Recent onset of - Fever - Productive cough- TLC- CXR
Why CAP- Healthy adult with no H/O hospitalization in recent past & was not taking any antibiotics
Common Outpatient Bacterial Etiologies
AntibioticsAntibiotics
Oral macrolide Erythromycin Azithromycin Clarithromycin
This patient’s pneumonia is mild
Previously healthy
No antibiotics in past 3 months
In patients who are older, have comorbid illnesses Levofloxacin Moxifloxacin
In patients treated with antibiotics within the last 90 days. Respiratory quinolones
MoxifloxacinLevofloxacinGemifloxacin or
B- lactam Amoxicillin + ClavunateCefuroxime
Beta-lactam + macrolide
Ceftriaxone or cefotaxime
Erythromycin, azithromycin, or clarithromycin
OR
Fluoroquinolone with antistreptococcal activity
Levofloxacin or moxifloxacin
Trimethoprim/sulfamethoxizole x 3 days
women with risk factors, complicated UTI
Fluoroquinolone x 3 days: Ciprofloxacin Norfloxacin Ofloxacin
Nitrofurantoin x 7 days
Initial drug selections:
Fluoroquinolones
Ciprofloxacin Levofloxacin
Cephalosorin
Ceftriaxone Cefotaxime + Amikacin
57 years male painful rash on his right leg. 5 days ago he developed a blister on his foot after wearing a new pair of shoes.
c/o fever with chills
PMHx – COPD, high cholesterol
Social – stopped tobacco two years ago.
Exam
Temp 101.2 otherwise stable , APPP
Exam unremarkable except for
Lungs – few inspiratory rales
Right leg …
Outpatient Treatment: non-MRSA
Antistaphylococcal penicillinDicloxacillinFirst-generation cephalosporin Cephalexin
Inpatient Treatment: non-MRSA Amoxicillin + Clavunate
Clindamycin is a good alternate with penicillin allergy
Surgical opinion
A 43 year old male presents with 10 days of purulent rhinorrhea, subjective fevers, and facial
headaches.
PMHx – HTN, high cholesterol
Meds – lisinopril/HCTZ
FamHx – noncontributory
Exam
HEENT – VS normal tenderness over right maxillary sinus
Exam otherwise unremarkable
Diagnosis?
Sinusitis
Mild Acute Bacterial Sinusitis (ABS)Amoxicillin
Amoxicillin/clavulanate
Cefuroxime axetil
CefpodoximeOr
antistrep. fluoroquinolones:LevofloxacinMoxifloxacin
Drug option in the case of allergies to penicillin and cephalosporin with Mild ABS:
◦ Doxycycline
◦ Trimethoprim/sulfamethoxizole
◦ Azithromycin
◦ Clarithromycin
Drug option in the case of allergies to penicillin and cephalosporin with Moderate to Severe ABS:
◦ Antipneumococcal fluoroquinolone:
Levofloxacin Moxifloxacin
42 years male with 5 days of progressive diffuse headache, mildly stiff neck,fever vomiting, confusion.
PMHx – none known
PSHx - none
Exam VS: T 100.9, Pulse 96, RR 16, BP 138/82
Gen: mildly ill appearing
Mental status: orientation to place & person not time
HEENT: mild photophobia
Neck: mild pain with flexion (kernig sign +ve )
Skin: no rash
RS/CVS - WNL
Lab.-
TLC - 16000
DLC - N80 L18
CECT Head - normal study
CSF - TLC – 412DLC – N 96 L4protein – 110mg/dlsuger - 23 mg/dl
Adults(<55years) and children>3 months old: High dose ceftriaxone or cefotaxime
+ Vancomycin 1gm IV BD
Adults > 55years of age , patient with alcoholism or other debilitating illness
High dose ceftriaxone /cefotaxime+ Vancomycin 1gm IV BD
+ Ampicillin 2gm/ 4horly
2gm IV BD
Cholera: Tetracycline 250 mg 6-hourly for 3 days,Doxycycline 300 mg single dose or
Ciprofloxacin 1 g in adults Bacillary Dysentery:
Ciprofloxacin 500 mg 12-hourly for 3 days Helicobacter pylori Infection:
Two antibiotics (from amoxicillin, clarithromycin and metronidazole) for 7 days
Aetiology: Salmonella typhi and Salmonella paratyphi A and B
Ciprofloxacin 500 mg 12-hourly
Ofloxacin 400 mg every 12 hourly
Ceftriaxone 2gm IV BD
Azithromycin 1gm once daily x 5 days
Treatment should be continued for minimum 10 days. Or
5 days after resolution of fever
Aetiology (pyogenic): E.coli, various streptococci (amoebic): Entamoeba
histolytica Management:o Pyogenic: Combination of antibiotics e.g3rd gen
cephalosporin, gentamicin and metronidazole
o Amoebic: Metronidazole (800 mg 8-hourly for 10 days) or tinidazole (2 g daily for 3 days)
Luminal amoebicide-diloxanide furoate (500 mg 8-hourly for 10 days)
Gastro-Intestinal: Ancylostoma, Ascaris:
Albendazole 400 mg single dose or Mebendazole 100 mg 12 hourly for 3 days
Tissue parasite:
Filariasis: Caused by Wuchereria bancrofti
Treatment: Diethylcarbamazine 6 mg/kg body wt. orally in 3 divided doses for 12 days.
Avoid tetracycline Staining of teeth and bones in babies Acute yellow atrophy of lever , pancreatitis in mother
Avoid sulfa drugs in the third trimester May be associated with kernicterus
Avoid aminoglycosides Kidney toxicities Can cause foetal ear damage
Fluoroquinolones Concerns about cartilage development
Treat the Mother first and the baby will appreciate it
Penicillins and cephalosporins are generally safe in pregnancy.
Macrolides are generally safe
- They may increase nausea early on
Is antibiotic necessary
What is the most appropriate antibiotic
H/O
Allergy
Pregnancy
Renal dysfunction
Liver Disease Dose/Frequency/Route/Duration
Monitor side effects