Bacteria

Aerobe Anaerobe Facultative anaerobe Microaerophilic

Gram (+) Bacilli Corynebacterium Clostridium
Listeria Actinomyces
Bacillus
Cocci Staphylococcus (Catalase (+)) – Coagulase (+)/(-)
Streptococcus
Enterococcus
Gram (-) Bacilli Pseudomonas Bacteroid Eneteric (coliform) Escherichia
(oxidase +ve) Fusobacterium (Ferment glucose) Salmonella
Acinetobacter Porphyromonas Shigella
Brucella Prevotella Klebsiella
(coccobacilli) Proteus
Vibrio (curved) (oxidase +ve)
Non-enteric Haemophilus (coccobacilli)
Chlamydia (rod or Brecella (coccobacilli)
cocci) Yersinia
Bordetella
Legionella
Cocci Neisseria Veillonella
Curved/spiral Leptospira Campylobacter
 Helicobacter
Arcobacter
Acid fast
Cell wall Mycoplasma
deficient

Spirochaetes: Trepnoema (gram –ve), borrelia

S. aureus: DM, hemodialysis, IV drug users

Antibacterial

Beta lactam
- Bind and in inhibit PBP (tranpeptidase)  bacterial cell wall weaks + autolysin activated
- Bacteriocidal
- Penicillin G
 Gram +ve and –ve cocci, gram +ve bacilli, spirochete (same as erythromycin)
 Limitations
- unstable in stomach acid
- short duration of action
- narrow spectrum
- poor penetration into CNS
- resistance developed largely due to β-lactamase
- allergy in some susceptible patients
- Aminopenicillin (e.g. ampicillin, amoxicillin)
 Similar to penicillin G, but more effective vs Gram-ve rod (more hydrophilic groups allow drug entry into gram-ve bacteria via proins)
 Acid stable, good oral bioavailability (amoxicillin > ampicillin)
- Antipseudomonal penicillins (e.g. piperacillin, tacarcillin)
 Same antibacterial spectrum as ampicillin – gram –ve rod
 Highly effective vs pseudomonas aeruginosa
- Beta-lactamase inhibitor (e.g. clavulanate, tazobactam, sulbactam)
 Potent irreversible inhibitor of beta-lactamases
- Cephalosporin
 Broad spectrum vs gram +ve and –ve, some vs anaerobes
 1st: Gram +ve cocci, gram-ve rod
 2nd: Gram +ve cocci, gram –ve cocci, gram –ve rod
 3rd: Gram –ve cocci, gram-ve rod (penetrate CNS)
 IM, only a few are orally active (e.g. cefuroxime)
 Renal excretion (some exceptions, e.g. ceftriaxone)
 Adverse effect/disadvantage
 Oral cephalosporin cause GI irritation
 Allergic reaction
 Infrequent nephrotoxicity
 Very expensive especially parenteral preparation
- Monobactam (e.g. aztreonam)
 Gram –ve aerobes only
 Resistant to beta-lactamases
 Low immunogenic potential  can be used for patients allergic to penicillin
- Carbapenem (e.g. imipenem)
 Widest spectrum beta-lactam
 Resistant to beta-lacatamases
 Cilastatin (protease inhibitor) formulated with imipenem to protect it from rapid degradation by a renal dehydropeptidase to an
inactive nephortoxic metabolite
 Used in UTI and other severe infections
Cotrimoxazole
- Inhibit 2 sequential steps in folate metabolism
 Sulphonamide: dihydropteroate synthetase
 Trimethoprim: dihydrofolate reductase
- Synergistic effect against gram +ve and –ve (pneumocystic jiroveci, gram +ve bacilli, gram –ve rods)
- Side effects of sulphonamide
 Allergy
 GI disturbance (e.g. nausea, vomiting, diarrhea)
 Urinary tract disturbance (e.g. cystalluria, hematuria, obstruction)
 Hematopoietic disturbance (e.g. anemia, granulocytopenia, thrombocytopenia)
 Danger of kernicterus in newborns (displacement of bilirubin from binding sites on plasma albumin)
- Side effects of trimethoprim
 Folic acid deficiency (e.g. megaloblastic anemia, leucopenia, grnulocytopenia)

Aminoglycoside
- Gram –ve bacilli, some facultative anaerobes
- Streptomycin (vs TB)
- Bind to 30S

Quinolone
- Nalidixic acid (1st generation)
 Urinary antiseptics, no systemic effect
 Effective against most gram –ve bacteria causing recurrent UTI infections
- Fluoroquinolone
 Inhibit bacterial DNA gyrase (topoisomerase II used in negative supercoiling the DNA) (gram –ve)
 Inhibit topoisomerase IV used to separate DNA strand after replication (gram +ve)
 2nd generation quinolone (e.g. ciprofloxacin, ofloxacin): expanded gram –ve, some gram +ve and atypical organism
 3rd (e.g. levofloxacin): expanded gram –ve, gram +ve and atypical
 4th (e.g. moxifloxacin, gemifloxacin): maintained gram –ve, improved gram +ve, gained anaerobic coverage
- Adverse effect
 GI symptoms, CNS problems, photosensitivity
 Ruptured tendon in adults
 Contraindicated in children, nursing mothers and pregnancy (arthropathy potential)
- Resistance: Eflux pump, and mutation of target gene

Macrolide
- Irreversibility bind to 50S subunit of bacterial ribosome  inhibit translocation of polypeptide chain from A-site to P-site  inhibit bacterial
protein synthesis
- Bacteristatic
- Active vs most common pathogens of community acquired pneumonia, including atypical agents
- Erythromycin: gram +ve, same as penicillin G, for patients allergic to penicillin
- Clarithromycin: Slightly greater activity than erythromycin. Gram +ve, intracellular pathogens (e.g. Chlamydia, Legionella, Moraxella)
(concentrate in phagocytes)
- Azithromycin: Slightly less active than erythromycin vs gram +ve but enhanced activity vs some gram –ve (e.g. H. influenza)
- Telithromycin: similar to azithromycin, gram –ve, effective vs macrolide-resistant strains
- Elimination: Erythromycin and telithromycin extensively metabolized
 Erythromycin and azithromycin concentrated and excreted in bile in active form, undergo enterohepatic circulation
- Adverse effect
 Relatively non-toxic
 Gi disturbance (due to stimulation of motilin receptors)
 Taking erythromycin estolate ester preparation for >1-2 weeks can cause cholestatic hepatitis
 Potential risk of arrhythmia (QT interval prolongation)
 Caution in patients with liver disease

Clindamycin
- Properties similar to erythromycin
- Spectrum similar to erythromycin vs gram +ve
- Mainly for severe anaerobic infections caused by Bacteroid fragilis
- C. difficile always resistant! Overgrown C. difficile release toxic which may caused potentially fatal pseudomembranous colitis

Tetracycline (e.g. doxycycline, minocycline)

- Bind 30S ribosome  prevent access of amino acid-tRNA to the acceptor site of mRNA ribosome complex  prevent addition of amino
acid to the growing peptide chain
- Bacteriostatic
- Broad spectrum, indicated in a wide variety of uncommon infections (e.g. Rickettsia, Chlamydia, Mycoplasma, spirochetes and protozoa)
- Resistance:
 Impaired influx/increased efflux (major)
 Ribosome protection due to production of proteins that interfere with tetracycline binding to ribosome
 Enzymatic inactivation
- Absorption: depend on acid lability, lipid solubility an d complex formation with metal ions, peak plasma concentration achieved in 2-4
hours
- Distribution: Well distributed (including pleural and synovial fluid, aqueous humor and abscess fluid), minocycline can penetrate to CSF, can
cross placental barrier and accumulate in fetal boens and dentition, thus delay boen growth
- Elimination: Metabolized in liver and eliminated in kidney. Doxycyline excreted in bile and feces (for renal insufficient patients)
- Adverse effects
 Local tissue irritation (avoid IM)
 Gi irritation and superinfection
 Hepatotoxicity
 Permanent teeth discoloration in children
 Phosensitization
 Vestibular problems
- Doxycycline:
 longer duration of action
 90-100% absorbed on oral administration
 absorption reduced by only 20% with milk or food
 not accumulated in kidney
- Glycylcycline (e.g. tigecycline): derived from tetracycline
 Multi-resistant gram +ve, some gram –ve and anaerobic
 Not effective vs proteus and pseudomonas
 Biliary excretion
 For complicated skin and soft tissue and complicated intra-abdominal infections
Glycopeptide (e.g. vancomycin)
- Blocks bacterial cell wall synthesis: bind D-Ala-D-Ala end of peptide through 5 H bonds  block cross-linking
- Resistance: alter terminal to D-Ala-D-lactate which removes a key H-bond (decreased affinity to vancomycin)
- Bactericidal
- Effective vs many drug-resistant bacteria
- Reserved for serious infections in penicillin-allergic patients and vs resistant organisms (e.g. MRSA and MRSE)
-
Nitrofurantoin

Chlorampheniol

Metronidazole
- Anaerobic (e.g. Bacteroid, Clostridium), protozoal (e.g. entamoeba, giardia)