Bugs and Drugs A Review of Antibiotics

1. Bugs and DrugsA Review of Antibiotics Curtis M. Grenoble, MHS, PA-C Lock Haven University

2. Lecture Outline • Mechanisms of Action • Mechanisms of Resistance • Bacterial Resistance • Principles of Therapy • Choosing an Antibiotic • Gram positives, gram negatives & anaerobes • Case Scenarios

3. Mechanisms of Action • Goal of antibiotic treatment: • Limit host toxicity • Maximize specific microbe toxicity • Bacteriocidals kill bacteria • Bacteriostatics inhibit further growth • Allowing immune system to regain control

4. Mechanisms of Action • Common bacteriocidals • β-Lactams • Penicillins • Cephalosporins • Carbapenems • Monobactams • Aminoglycosides

5. Mechanisms of Action • Common bacteriostatics • Sulphonamides • Tetracyclines • Chloramphenicol • Macrolides • Erythromycin • Clarithromycin • Azithromycin • Trimethoprim(often used along with sulfonamides i.e. Bactrim)

6. Mechanisms of Resistance • Intrinsic Resistance • Analogous to innate (non-specific) human immunity • Examples: • Obligate anaerobic bacteria to aminoglycosides • Gram (–) bacteria to vancomycin • Acquired Resistance • Analogous to specific action of human immunity • Bug, over time, develops resistance to specific mechanism of action • Mutation of resident genes, or • Acquire new genes and incorporate into own DNA • Major problem with over-prescribing antibiotics • Pt demands (stronger) antibiotic and practitioner gives in (viral URI, viral pharyngitis) • Selects for those organisms with resistance, proliferation, further mutation

7. Principles of Antibacterial therapy • First, attempt to specifically ID the bug if accessible • Obtain culture • Stain specimen and ID under microscope • Cocci • Bacilli • C&S • Choose narrowest spectrum and most inexpensive drug that will effectively eliminate the infection.

8. Principles Of Antibiotic Therapy • Susceptibility • If peak serum concentration of drug is 4-times the MIC (Minimum Inhibitory Concentration) • Breakpoint • Concentration of antibiotic that separates susceptible from resistant bacteria

9. Principles of Antibacterial Therapy • Pharmacodynamics • Concentration dependent • e.g. Aminoglycoside once daily • Time dependent • e.g. Amoxil for pneumococcal AOM • Need to maintain high levels of abx over MIC x number of days • More difficult for drug to reach inner ear • Younger male with UTI • TB therapy

10. Principles of Antibiotic Therapy • Site of Infection – Difficult to treat • Meningitis – blood-brain barrier, some don’t cross at all, others not enough • Bacterial endocarditis – Growth may be difficult to penetrate and often possess both innate and acquired immunity • Osteomylitis – dense tissue, low vascularity • Intraocular infections – no blood in vitreous, special vessels mediate exchange of nutrients with vitreous • Abscesses – encapsulated, thick, fibrous, poorly vascularized • Need to I&D

11. Principles of Antibacterial Therapy • Site of Infection – Easy to Treat • Urinary Tract Infection • High drug concentration in urine due to elimination via kidneys • In the past, PCN purified from urine to reuse before made synthetically

12. Principles of Antibacterial Therapy • Empiric Therapy • Life-threatening infection • Need to treat immediately with best guess of causative organism • Based on signs, symptoms and epidemiology • Need to know most likely causative organism in a given institution • Community-acquired Infection • Need to know most likely causative organism in: • Community • Population • Age group

13. Choice of Antibacterial Drugs • β-Lactams • Penicillins • β-lactamase susceptible – Penicillin G (parenteral) V (oral), ampicillin, amoxicillin, ticarcillin • β-lactamase resistant – Methicillin, oxacillin, nafcillin, cloxacillin, dicloxacillin • Amoxicillin-Clavulanic acid (Augmentin) • Cephalosporins • 1st Generation – Cephalexin, cephradine, cephadroxil • 2nd Generation – Cefaclor, cefoxitin, cefuroxime, cefdinir, ceftibuten • 3rd Generation – Ceftriaxone • 4th Generation - Cefepime • Carbapenems • Imipenem, meropenem, ertapenem • Monobactams • Aztreonam

14. Choice of Antibacterial Drugs • Non-β-Lactams • Vancomycin • Aminoglycosides – streptomycin, gentamicin, tobramycin • Macrolides and Ketolides – erythromycin, azithro-, telithro- • Licosamides – clindamycin • Chloramphenicol • Tetracyclines – tetracyclin, doxycycline, minocycline • Fluoroquinolones – ciprofloxacin, gati-, moxi-, levo-, etc • Rifampin • Metronidazole

15. Choice of Antibacterial Drugs • Penicillin G and V Spectrum • Spirochetes • Treponemapallidum (Syphilis) • Borrelia (Lyme Dz) • Streptococci • Groups A and B • Many strains of S. pneumoniae • Clostridium species • Penicillin G and V Sensitive Diseases • Syphilis • Strept infections groups A and B • Tetanus

16. Choice of Antibacterial Drugs • Ampicillin Spectrum • Enterococcusfaecalis • Salmonella • Haemophilusinfluenzae • Ampicillin Diseases • E. faecalis UTI • Salmonellosis • H. flu AOM & epiglottitis • Amoxicillin-Clavulanic Acid (Augmentin) • Pasturellamultocida • Dog/Cat bite • Wounds obtained in wet environment

17. Choice of Antibacterial Drugs • 1st Generation Cephalosporins Spectrum • Escherichia Coli • Klebsiellapneumoniae • Proteus mirabilis • 1st Generation Cephalosporins Diseases • Community acquired UTI • UTI secondary to indwelling bladder catheter • Klebsiellapneumoniae pneumonia (alcoholics, DM, lung dz) • Abdominal infection • Surgical site/soft tissue infection

18. Choice of Antibacterial Drugs • Oral 2nd Generation Cephalosporins Spectrum • Gram positive cocci (streptococci, staphylococci) • Haemophilusinfluenzae • Oral 2nd Generation Cephalosporins Diseases • Otitis media • Sinusitis • Lower respiratory tract infection

19. Choice of Antibacterial Drugs • Parenteral 3rd Generation Cephalosporins Spectrum • Enteric gram-negative rods • Pseudomonas • Listeria • Parenteral 3rd Generation Cephalosporins Diseases • Gonorrhea (Ceftriaxone) • Salmonellosis • Listeria bacterial menningitis

20. Choice of Antibacterial Drugs • 4th Generation Cephalosporins Spectrum • Gram-positive bacteria • Gram-negative bacteria • P. aeruginosa • Enterobacteriaceae • 4th Generation Cephalosporins Diseases • Intra-abdominal infections • Respiratory tract infections • Skin infections

21. Choice of Antibacterial Drugs • Vancomycin Spectrum • Gram-positive cocci (enterococci, streptococci, staphylococci) • Vancomycin Diseases • Methicillin-resistant staph aureus • Second-line for most gram-positive • P.O. in pseudomembranous colitis • Not absorbed when taken P.O. • Becomes “topical” tx for UC • Use Vanco sparingly and only in demonstrated cases of resistance to β-lactams to prevent MRSA from developing resistance • Not for routine empiric therapy

22. Choice of Antibacterial Drugs • Aminoglycoside spectrum • Gram-negative aerobes • Staph • No activity against anaerobic bacteria or in acidic/low oxygen • Aminoglycoside diseases • SevereURI • Gram-negbacteremia • Tularemia, plague, brucellosis – Streptomycin (2nd line TB)

23. Choice of Antibacterial Drugs • Macrolides spectrum (bacteriostatic) • Gram-positive bacteria • Legionella • Chlamydia • Helicobacter pylori • Macrolides diseases • Streptpharyngitis in PCN-allergic (erythromycin- don’t need broader spectrum if not indicated) • Community-acquired pneumococcal pneumonia • Legionnaire’s disease • Gastric ulcers

24. Choice of Antibacterial Drugs • Tetracyclines spectrum (bacteriostatic) • Gram-positive bacteria • Gram-negative bacteria • Borrelia (Lyme disease) • Chlamydia • Tetracyclines diseases • Bacterial chronic bronchitis • Lyme disease • Skin and soft-tissue infections • Syphillis • Acne vulgaris – suppresses resident P. acnes flora, prevents from chopping non-irritating long chain FA to irritating short-chain FA

25. Choice of Antibacterial Drugs • Sulfonamides & Trimethoprim spectrum • E. Coli • H. flu • Other gram-neg bacteria • Sulfonamides & Trimethoprim diseases • Community-acquired UTI (Bactrim) • Otitis media • Bacterial URI

26. Choice of Antibacterial Drugs • Fluoroquinolones spectrum • Pseudomonas aeruginosa • Other gram-neg bacteria • Fluoroquinolones diseases • UTI • Bacterial gastroenteritis • Community-acquired pneumonia

27. Choice of Antibacterial Drugs • Metronidazole spectrum • Anaerobic bacteria only • Mostly gram-negative • Bacteroides species • Also an anti-parasitic • Metronidazole diseases • Tough to treat anaerobic abscesses of abdomen, brain or lung • Bacterial vaginosis • Drug of choice: Antibiotic-associated pseudomembranous colitis

28. Duration of Therapy & Treatment Failure Vs. Success • Treatment duration varies according to disease • Refer to drug guides for dosage and duration • No trials for many diseases, therefore duration not firmly established • Duration • Not too short – need to fully treat/resolve infection • Need to avoid resistance • Success = no relapse when treatment is d/c • New infection with different organism is considered a success for initial infection • Failure = recurrence of infection with identical organism • Failures need >4 wk course & combination treatment

29. Common Side-Effects and Adverse Reactions • All antibiotics can elicit allergic responses • Mild, annoying rashes, etc. • Anaphylaxis • Stevens-Johnson syndrome • All antibiotics target normal flora in addition to pathogens • May lead to overgrowth of Candida – Yeast Infxn • May lead to overgrowth of Clostridium difficile • Mild diarrhea to severe life-threatening complications (pseudomembranous colitis) • D/C offending antibiotic • Supportive therapy • Drug of choice: Metronidazole (Vancomycin 2nd line)

30. Common Side-Effects and Adverse Reactions • β-Lactams • 1-4% of treatment courses result in allergic reaction • Severe: anaphylaxis, TEN, Stevens-Jonhnson syndrome, pseudomembranous colitis (rare) • Mild: rash, GI upset, diarrhea • Vancomycin • Red Man Syndrome – pruritus, flushing, erythema • Phlebitis at infusion site • Nephrotoxicity and Ototoxicity rare • Aminoglycosides • Nephrotixicity – accumulation in peritubular space • Ototoxicity – can destroy hair cells, auditory/vestibular • Neuromuscular depression with rare respiratory depression

31. Common Side-Effects and Adverse Reactions • Macrolides • Serious adverse reactions very rare • GI side effects – burning, nausea, nomiting (up to 50% of pts) • Hepatotoxicity and ototoxicity rare • QT Prolongation • Lincosamides • GI distress • Pseudomembranous colitis secondary to C. diff toxin (Metronidazole) • Chloramphenicol • Bone marrow suppression • Gray syndrome (cyanosis, hypotension, death) – infants

32. Common Side-Effects and Adverse Reactions • Tetracyclines • Contraindicated in children <8 yrs old • Mottling of permanent teeth • Contraindicated in pregnancy – teratogenicity • GI distress • Phototoxic skin reactions • Sulfonamides and Trimethoprim • Generally safe • Minor skin rashes to erythemamultiforme and SJS, TEN • Hematologic complications – agranulocytosis, anemia • Renal insufficiency caused by crystal formation

33. Common Side-Effects and Adverse Reactions • Fluoroquinolones • GI distress – nausea, diarrhea (<5%) • CNS effects – insomnia, dizziness (<5%) • Phototoxicity • Metronidazole • GI distress – nausea • Metallic taste, stomatitis, glossitis • Contraindicated in pregnancy - mutagenicity Warning: Cautious use of Fluoroquinolones due to risk of tendon ruptures associated with their use. Contraindicated for use in pregnant women and patients < 18 yrs of age because of evidence of cartilage damage in developing joints.

34. Case Scenario 1 • 30 year-old male presents with dysuria and a painful, swollen testicle that is red and tender. • Diagnosis? • Bug? • Drug?

35. Case Scenario 1 • 30 year-old male presents with dysuria and a painful, swollen testicle that is red and tender. • Diagnosis? Orchitis • Bug? Neisseriagonorrhoeae or Chlamydia trachomatis • Drug? Ceftriaxone & Doxycycline

36. Case Scenario 2 • A 50 year-old lifetime smoker presents with productive cough of dark, jelly-like sputum. He has rales in the right upper lung field. His CXR reveals a RUL infiltrate. • Diagnosis? • Bug? • Drug?

37. Case Scenario 2 • A 50 year-old lifetime smoker presents with productive cough of dark, jelly-like sputum. He has rales in the right upper lung field. His CXR reveals a RUL infiltrate. • Diagnosis? Pneumonia • Bug? H. influenza • Drug? Levofloxacin (Levaquin) or Ceftriaxone or Augmentin

38. Case Scenario 3 • A 12 year-old girl suffers a cat bite to her LIF (left index finger). The fingers are flexed and there is redness and tenderness along the flexor tendon surface extending into the forearm. She cannot extend the finger. • Diagnosis? Tenosynovitis • Bug? Pasturella • Drug? Amoxicillin/Clavulanic Acid (Augmentin)

39. Case Scenario 4 • A 35 year-old, healthy, recently sexually active female develops dysuria, urgency, and polyuria. She has suprapubic tenderness and is afebrile. • Diagnosis? • Bug? • Drug?

40. Case Scenario 4 • A 35 year-old, healthy, recently sexually active female develops dysuria, urgency, and polyuria. She has suprapubic tenderness and is afebrile. • Diagnosis? UTI • Bug? E. Coli • Drug? Bactrim

41. Case Scenario 5 • A 17 year-old returns from a rock concert where hundreds of people camped outside near a stream overnight. She has abdominal pain, high fever, and severe, bloody diarrhea. • Diagnosis? • Bug? • Drug?

42. Case Scenario 5 • A 17 year-old returns from a rock concert where hundreds of people camped outside near a stream overnight. She has abdominal pain, high fever, and severe, bloody diarrhea. • Diagnosis? Gastroenteritis • Bug? Shigella • Drug? Ciprofloxacin

43. Case Scenario 6 • A middle-aged man returns for a third episode of a painful, red, warm nodule on the nape of his neck tha recurs despite antibiotics and I&D. • Diagnosis? • Bug? • Drug?

44. Case Scenario 6 • A middle-aged man returns for a third episode of a painful, red, warm nodule on the nape of his neck tha recurs despite antibiotics and I&D. • Diagnosis? Furuncle/Carbuncle • Bug? MRSA • Drug? Vancomycin

45. Case Scenario 7 • A 32 year-old nonsmoker complains of a cough of 3 weeks duration. Placed on amoxicillin 10 days ago without relief. Pt is afebrile. • Diagnosis? • Bug? • Drug?

46. Case Scenario 7 • A 32 year-old nonsmoker complains of a cough of 3 weeks duration. Placed on amoxicillin 10 days ago without relief. Pt is afebrile. • Diagnosis? Pertussis (whooping cough) • Bug? Bordatellapertussis • Drug? Erythromycin

47. Case Scenario 8 • An elderly male from an ECF is hospitalized. He suffered a CVA and has altered consciousness. 2 days s/p admission, he becomes febrile and septic. CXR shows large upper lobe infiltrates. • Diagnosis? • Bug? • Drug?

48. Case Scenario 8 • An elderly male from an ECF is hospitalized. He suffered a CVA and has altered consciousness. 2 days s/p admission, he becomes febrile and septic. CXR shows large upper lobe infiltrates. • Diagnosis? Aspiration pneumonia • Bug? Bacteroidesfragilis • Drug? Clindamycin

49. Case Scenario 9 • A healthy young adult male marathon runner steps on a nail that punctures his running shoe producing a wound in the sole of his left foot. The wound becomes reddened, warm and painful. The infection is localized around the puncture site on exam and the patient’s exam is otherwise normal. • Diagnosis? • Bug? • Drug?

50. Case Scenario 9 • A healthy young adult male marathon runner steps on a nail that punctures his running shoe producing a wound in the sole of his left foot. The wound becomes reddened, warm and painful. The infection is localized around the puncture site on exam and the patient’s exam is otherwise normal. • Diagnosis? Puncture wound, wet environment • Bug? Pseudomonas aeruginosa • Drug? Augmentin (or Cefepime)