Case 2: Yaser Kallas - Sepsis

Antibiotics: Classes

Cell wall inhibitors

• Beta-lactams

  • Penicillins

  • Cephalosporins

  • Carbapenems

• Beta-lactamase inhibitors

• Glycopeptides

Cell membrane disruptors

• Lipopeptides

Protein synthesis inhibitors

• Aminoglycosides

• Tetracyclines

• Macrolides

• Lincosamides

• Oxazolidinones

DNA synthesis inhibitors

• Fluoroquinolones

• Nitroimidazoles

Folic acid synthesis inhibitors

• Sulfonamides

Antimycobacterial drugs

• Nitrofurans

Beta-Lactams: Penicillins

Ex:

• Penecillin G/V

• Oxacillin

• Amoxicillin

• Ampicillin

• Piperacillin

Coverage:

• Gram+

• Neisseria spp. (gram-)

• VRE: Ampicillin

Uses:

• Resp

  • Strep. pharyngitis

  • Pneumonia

• CNS

  • Bacterial meningitis

• Blood

  • Syphilis

Beta-Lactams: Cephalosporins

Ex:

• 1st Gen: Cephalezin, cefazolin

• 2nd Gen: Cefaclor

• 3rd Gen: Ceftriaxone, cefixime

• 4th Gen: Cefepime

• 5th Gen: Ceftaroline

Coverage:

• 1st Gen: Gram+ cocci

• 2nd Gen:

  • Gram+ cocci

  • Gram- bacilli

• 3rd Gen: Gram- (empiric)

• 4th Gen:

  • Gram+ cocci

  • Gram- bacilli

• 5th Gen:

  • MRSA

  • Enterococcus faecalis

Uses:

• 1st Gen:

  • Skin/soft tissue infections

  • Endocarditis

• 2nd Gen:

  • Diabetes-related foot infections

  • Bites

  • Community-acquired pneumonia + comorbidities

• 3rd Gen:

  • Bacterial meningitis

  • Infections in hospitalized pts (pneumonia, sinusitis, pyelonephritis, peritonitis)

• 4th Gen:

  • Complicated UTI

  • Catheter-related infections

  • Pneumonia in hospital

• 5th Gen:

  • MRSA

  • Infective endocarditis

Beta-Lactams: Carbapenems

Ex:

• Meropenem

• Imipenem

Coverage:

• Gram+ and gram- aerobes

• Klebsiella spp.

Uses:

• Resp

  • Pneumonia

    • Hospital-acquired

    • Ventilator

• GU

  • Complicated UTI

• CNS

  • Bacterial meningitis

• Blood

  • Febrile neutropenia

Beta-Lactamase Inhibitors

Ex: Combine with penicillin

• Clavulanate + amoxicillin

• Avibactam + ceftazidime

• Sulbactam + ampicillin

• Tazobactam + piperacillin

Glycopeptides

Ex:

• Vancomycin

• Telavancin

• Dalbavancin

Coverage: MRSA

Uses:

• Resp

  • Pneumonia

• Skin

  • Skin/soft tissue infections

• Heart

  • Endocarditis

• CNS

  • Meningitis

  • Encephalitis

• Blood

  • Bacteremia

• Bone

  • Osteomyelitis

• Surgical prophylaxis

  • Penecillin allergy

Lipopeptides

Ex: Daptomycin

Coverage:

• MRSA

• VRE (ampicillin not available)

Uses:

• Skin

  • Skin/soft tissue infections

• Blood

  • Bacteremia

• NOT FOR:

  • Pulmonary infections

  • CNS infections

Aminoglycosides

Ex:

• Gentamicin

• Tobramycin

• Streptomycin

Coverage:

• Gram-

  • Enterobacteria (E. coli, enterobacter spp., Klebsiella spp.)

• Gram+

  • Mycobacterium (M. tuberculosis)

• Yersinia pestis

Uses:

• Resp

  • Pneumonia

    • Hospital-acquired

    • Ventilator

  • CF

• GU

  • Pyelonephritis

  • Complicated UTI

• Heart

  • Infective endocarditis

• CNS

  • Meningitis

Tetracyclines

Ex:

• Tetracycline

• Doxycycline

• Omadacycline

Coverage:

• Gram+ aerobic

  • Staph

  • Strep

  • Enterococcus

• Gram-

  • Enterobacterales

  • H. influenzae

• Anaerobic

• Intracellular organisms

• Protazoan parasites

Uses:

• Resp

  • Pneumonia

• GI

  • PID

• Blood

  • Malaria

  • Lyme disease

Macrolides

Ex:

• Erythromycin

• Azithromycin

• Clarithromycin

Coverage:

• Gram+

  • Staph

  • Strep

  • Mycoplasma pneumoniae

• Gram-

  • H. pylori

• Atypical

Uses:

• Resp

  • Pneumonia

    • Community-acquired

  • Pertussis

• GI

  • Campylobacter gastroenteritis

  • H. pylori

• GU/STI

  • Chlamydia

  • GU infection

Lincosamides

Ex: Clindamycin

Coverage: Gram+ aerobic + anaerobic

Uses:

• Penicillin allergies

• GAS infections

  • Necrotizing fasciitis

  • Toxic shock syndrome

  • Strep pharyngitis

Oxazolidinones

Ex: Linezolid

Coverage:

• Gram+ aerobic

• MRSA

• VRE (ampicillin not available)

Uses:

• Resp

  • Pneumonia

    • Hospital-acquired

• Skin

  • Skin/soft tissue infections

• Blood

  • Bacteremia

• CNS

  • Meningitis

• Bone

  • Bone + joint infections

Fluoroquinolones

Ex:

• Ciprofloxacin

• Levofloxacin

• Enoxacin

Coverage: Gram-

• Mycoplasma pneumoniae

• Legionella pneumophilia

Uses:

• Resp

  • Pneumonia

    • Community-acquired

    • Atypical

  • COPD exacerbations

• GU/STI

  • Complicated UTI

  • Chlamydia

• GI

  • GI infections (salmonella)

• Bone

  • Bone + joint infections

Nitroimidazoles

Ex:

• Metronidazole

• Tinidazole

Coverage:

• Anaerobic

• Protozoa parasites

Uses:

• GU

  • Bacterial vaginosis

  • PID

  • Trichomoniasis

• GI

  • Abscesses

  • Giardiasis

Sulfonamides

Ex: TMP/SMX

Coverage:

• Gram+

  • MRSA

  • S. aureus

• Gram-

  • Enterobacter

  • E. coli

  • Neisseria meningitides

• Fungi

Uses:

• Resp

  • Pneumonia

  • Pneumocytis

• Skin

  • Skin/soft tissue infections

• GU

  • UTI

• CNS

  • Toxoplasmosis

  • Meningococcal disease (with penicillin allergy)

Nitrofurans

Ex: Nitrofurantoin

Coverage:

• Gram+

  • Enterococci

  • Group B strep

  • S. aureus

  • S. epidermidis

• Gram-

  • E. coli

  • Enterobacter

  • Shigella

  • Salmonella

  • Neisseria

  • Klebsiella

Uses:

• Uncomplicated UTI

Sepsis: Description

Life-threatening organ dysfunction from dysregulated infection response

Sepsis: Epidemiology

Risk factors…

• Young/age age

• Refugee status

• Prolonged admission → Nosocomial infections

• Recent antibiotic or corticosteroid use

• Immunocompromise

  • Chronic disease

  • Malnutrition

  • Smoking

  • Alcohol

  • HIV

  • Cancer + chemo

  • Liver disease

  • Splenectomy

Splenectomy

Increase susceptibility to encapsulated bacteria

Spleen:

• Filter RBCs + platelets = Remove defective cells

• Lymphatic tissue = APC presentation to immature T and B cells = Activation

• Macrophages phagocytose encapsulated bacteria

Sepsis: Etiology

Pathogens:

• Gram+ bacteria

  • S. aureus

  • S. pneumoniae

• Gram- bacteria

  • E. coli

  • Klebsiella spp.

  • Pseudomonas spp.

• Fungi

  • Candida spp.

Causes:

• Resp: Pneumonia

  • Most common

• Abdo: Abscess

• GU: Pyelonephritis