Bacterial Disease and Antibiotics Notes (comprehensive)

Bacteriology and Antibiotics: Comprehensive Notes

  • Bacterial classifications (prokaryotes)

    • Gram stain: Gram-positive (purple) vs Gram-negative (pink) based on membrane composition

    • Oxygen requirements: aerobic vs anaerobic

    • Shape: Coccus (spherical), Bacillus (rod-like), Spirochete (spiral)

    • Environment: intracellular vs extracellular

    • Atypical bacteria

    • Bacteremia: bacteria in the bloodstream

    • Sepsis: bacteremia with toxins causing systemic symptoms/signs

Cell envelope and wall

  • Cell envelope consists of two components found in both Gram-positive and Gram-negative bacteria:

    • Cytoplasmic (cell) membrane

    • Cell wall

  • Key differences:

    • Cell wall thickness is greater in Gram-positive bacteria

    • Gram-negative bacteria possess an outer membrane not found in Gram-positives

  • Functions and implications:

    • The cell wall maintains bacterial shape and protects against osmotic lysis in hypotonic environments

    • Inhibiting cell wall synthesis is usually bactericidal because the bacteria lack a protecting wall

    • Bacterial cell wall synthesis occurs during replication, so inhibitors are more active against rapidly dividing bacteria

    • Cell wall inhibitors are often reduced in effectiveness when used with bacteriostatic antibiotics that slow growth

Gram-positive vs Gram-negative features (visual summary)

  • Gram-positive: thick peptidoglycan layer, teichoic acids, no outer membrane

  • Gram-negative: outer membrane with lipopolysaccharide (LPS), thin peptidoglycan, periplasmic space

  • Illustrative terms (from slide content): Lipoproteins, DNA oligomers, super-antigens (protein), exotoxins (protein) for Gram-positives; outer membrane (OM) and lipopolysaccharide (LPS) for Gram-negatives; endotoxin concept tied to LPS

  • Endotoxin (LPS) is part of Gram-negative cell wall and may be released during growth or antibiotic treatment

Bacterial Pathogenesis – Invasion and Damage

  • Virulence factors enable disease-causing potential:

    • Pili (fimbriae): hair-like projections that promote adhesion to cells, tissue invasion, and adherence to other bacteria

    • Flagella: rotary motility aiding mobility, adhesion, and invasion

    • Enzymes: proteases and other enzymes that breach host defenses

    • Capsules: protection from immune system (phagocytosis evasion)

    • Spores: dormant, highly resistant forms (heat-resistant)

    • Biofilm: slimy extracellular matrix protecting bacteria from immune clearance

    • Toxins: toxins that injure host cells

Toxins

  • Bacterial toxins divide into:

    • Endotoxins: Lipopolysaccharide (LPS) components released from Gram-negative bacteria; can stimulate immune response at low levels but trigger cytokine release and coagulation cascades at high levels

    • Exotoxins: produced inside bacteria and secreted; can damage cell walls or disrupt cellular functions

  • Examples of exotoxins: Botulinum toxin, coagulases, exfoliative toxins, enterotoxins

Bacterial Pathogenesis - Evasion

  • Evasion mechanisms allow bacteria to multiply and cause disease:

    • Enzymes (e.g., proteases) that digest host proteins

    • Capsules that prevent phagocytosis

    • Horizontal gene transfer between bacteria

    • Bacteriophages (viruses) and plasmids (nonchromosomal DNA moving between bacteria via conjugation)

    • Biofilm formation on surfaces (implanted devices, teeth, epithelium)

Major mechanisms of bacterial antimicrobial resistance

  • Enzymatic inactivation or modification of drugs:

    • Beta-lactamase hydrolyzes the beta-lactam ring

    • Aminoglycoside-modifying enzymes (acetylating, adenylating, phosphorylating)

  • Decreased drug uptake or accumulation:

    • Reduced outer membrane permeability (intrinsic or acquired) and impaired transport

    • Antibiotic efflux pumps (e.g., tetracycline resistance)

  • Altered or lacking drug target sites:

    • Altered PBPs (beta-lactam resistance)

    • Altered ribosomal targets (aminoglycosides, macrolides)

    • Altered enzymatic targets (sulfonamides, trimethoprim, rifampin, quinolones)

  • Circumvention of drug action sequences:

    • Hyperproduction of drug targets or competitive substrates (e.g., certain Bactrim resistances)

Killing properties of antibiotics

  • Interval-dependent (time-dependent) killing:

    • The antibiotic exerts killing as long as the drug concentration remains above the MIC

    • Examples: beta-lactams and vancomycin

    • Notable concept: time above MIC governs effectiveness

  • Concentration-dependent killing:

    • The antibiotic continues to kill even after concentrations fall below the MIC due to the Post-Antibiotic Effect (PAE)

    • Higher peak concentration yields greater kill

    • Examples: aminoglycosides and fluoroquinolones

The Body Invaders: Friends or Foes?

  • Friends (commensals): Nonpathogenic microbiota essential for health

    • Colonize skin and mucous membranes; aid digestion; synthesize metabolites

  • Frenemies (opportunists): Usually harmless but cause disease when host defenses are compromised

    • Examples: Streptococcus pneumoniae, Group A Strep, Neisseria meningitidis, Haemophilus influenzae, Klebsiella pneumoniae in certain contexts; E. coli and other GI residents can cause infections when host is compromised

  • Foes (true pathogens): Can cause disease regardless of host status

    • Examples: Staphylococcus aureus, Salmonella typhi, Shigella, Treponema pallidum, Mycobacterium tuberculosis, etc.

General Antibiotic Principles

  • Diagnosis and treatment planning:

    • Determine infection site and host factors (age, immunocompromised status, comorbidities)

    • Identify most likely causative bacteria

    • Treatment modalities: Prophylactic, Empiric, Definitive

  • Key pharmacology concepts:

    • MIC: Minimum inhibitory concentration

    • Susceptible, Intermediate, Resistant categories

    • MBC: Minimum bactericidal concentration

    • Bioavailability: IV vs oral (PO) differences

    • Bacteriostatic vs bactericidal actions

    • Bacteriostatic: inhibits growth, relies on host immune clearance; often via protein synthesis inhibitors (e.g., sulfonamides, tetracyclines, macrolides)

    • Bactericidal: actively kills bacteria (often cell wall inhibitors like beta-lactams or cell membrane disruptors like daptomycin)

    • Severe infections (endocarditis, sepsis, osteomyelitis) often require bactericidal agents

  • Important relationships:

    • Drug activity can be influenced by bacterial growth phase

    • Combination therapy can be used for synergy but may impact activity depending on agents used

Antibiotic Interactions

  • Warfarin interaction: most antibiotics inhibit gut flora that synthesize vitamin K, potentiating warfarin effects

  • Fluoroquinolones: can chelate with cations (Mg, Ca) in the gut reducing absorption

  • Potential impact on oral contraceptives: some antibiotics can affect efficacy

Antibiotic Reactions

  • Hypersensitivity reactions: range from rashes to anaphylaxis; dose- and class-dependent

  • Adverse drug reactions: antibiotics are common causes of severe immune-mediated reactions

  • Cross-reactivity considerations:

    • PCN and other beta-lactams show cross-reactivity; patients with penicillin allergy may tolerate some cephalosporins depending on reaction history

Bacteriology: Staphylococcus aureus

  • Gram-positive aerobe; most virulent Staph species

  • Produces penicillinases (beta-lactamases) allowing MSSA to resist some penicillins

  • MRSA: altered penicillin-binding protein (PBP2a) that reduces beta-lactam efficacy; need non-beta-lactam antibiotics (e.g., vancomycin)

  • Common diseases: skin/soft tissue infections (abscesses), pneumonia (often hospital-acquired), endocarditis

Staphylococcal infections

  • Common presentations: furunculosis, pyogenic lesions, stye, carbuncles, bullous impetigo, paronychia

  • Deep infections: osteomyelitis, bacterial pneumonia, endocarditis

  • Toxin-mediated diseases: Ritter’s disease (scalded skin syndrome), toxic shock syndrome, staphylococcal food poisoning

Streptococcus

  • Hemolysis patterns on sheep blood agar:

    • Alpha (incomplete) hemolysis: Strep pneumoniae (diplococci with capsules), Strep viridans (chains; commensal)

    • Beta (complete) hemolysis: Strep pyogenes, Strep agalactiae

    • Gamma (non-hemolytic)

Streptococcal diseases

  • Pharyngitis: common viral causes; S. pyogenes (Group A) accounts for a minority of pharyngitis cases in adults; other organisms include Arcanobacterium haemolyticum, Neisseria gonorrhoeae, Chlamydia pneumoniae, EBV

  • Upper respiratory infections: sinusitis, otitis media

  • Impetigo, erysipelas, wound/burn infections, scarlet fever

  • Immunologic sequelae: rheumatic fever, acute glomerulonephritis

  • Cellulitis, necrotizing fasciitis, pneumococcal meningitis

Enterococcus

  • Gram-positive cocci: E. faecalis and E. faecium

  • Normal GI tract inhabitants; highly resistant; VRE (vancomycin-resistant enterococcus)

  • Clinically: opportunistic UTIs, wound infections, endocarditis

Anaerobes

  • Definition: cannot thrive in the presence of oxygen due to lack of protective enzymes (peroxidase, catalase, SOD)

  • Clostridia species produce toxins; spore-formers

    • C. botulinum, C. tetani, C. perfringens, C. difficile

Gram-negative aerobes

  • Enteric bacilli (Enterobacteriaceae): primarily Gram-negative rods

  • Normal flora in humans and animals; many opportunistic pathogens

  • Key genera: E. coli, Klebsiella, Proteus, Enterobacter, Salmonella, Shigella, Yersinia, etc.

  • Notable features: endotoxin (LPS) contributes to sepsis; capsules; various beta-lactamase enzymes

Escherichia coli (E. coli)

  • Normal flora; most common cause of UTI; can cause opportunistic infections and diarrheagenic disease

  • Septic shock risk due to LPS endotoxin

Klebsiella pneumoniae

  • Virulence: endotoxin, capsule; antimicrobial resistance (beta-lactamases)

  • Diseases: pneumonia, UTI, bacteremia

Proteus mirabilis

  • Virulence: endotoxin, flagella, urease production

  • Resistance: some beta-lactamases

  • Diseases: UTIs (cystitis, pyelonephritis); can cause stone formation (urolithiasis)

Pseudomonas aeruginosa

  • Highly antibiotic-resistant; thrives in moist environments (hot tubs, pools)

  • Common in CF patients; causes pneumonia, burn-wound infections, endocarditis, otitis externa, osteomyelitis, UTIs

Extended Spectrum Beta-Lactamase (ESBL)

  • Bacterial resistance due to enzymes destroying most beta-lactam antibiotics

  • Common in Gram-negative organisms; MDROs

  • Producers include E. coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae

  • ESBL producers may also produce carbapenemases (KPC)

Antibiotics (drug classes)

  • Cell wall inhibitors: β-lactams (penicillins, cephalosporins, carbapenems), vancomycin

  • Protein synthesis inhibitors: tetracyclines, fluoroquinolones, macrolides, aminoglycosides, linezolid, clindamycin

  • Folate inhibitors: sulfonamides, trimethoprim (TMP-SMX)

  • Others: nitrofurantoin, daptomycin

β-Lactam Drugs: sites of action

  • β-lactams bind to PBPs (penicillin-binding proteins)

  • PBPs drive peptidoglycan synthesis, forming a lattice that provides cell wall integrity

  • Different bacteria have different PBPs and affinities for specific β-lactams, influencing spectrum of activity

β-Lactam Drugs: penicillins

  • Grouped by activity:

    • Narrow-spectrum penicillins: Penicillin G, Penicillin V

    • Penicillinase-resistant penicillins: oxacillin, cloxacillin, dicloxacillin, nafcillin (primarily MSSA)

    • Extended-spectrum penicillins: amoxicillin, ampicillin (better for some Gram-positives and mild Gram-negatives); piperacillin, ticarcillin (active against Pseudomonas)

β-Lactam Drugs – adverse effects (penicillins)

  • Hypersensitivity reactions are common; true penicillin allergy occurs in about 7–23% of patients with a reported history

  • Hypersensitivity arises from degradation products (penicilloic acid) forming antigens

  • Immediate hypersensitivity (IgE-mediated) can cause urticaria or anaphylaxis; other reactions include serum sickness, interstitial nephritis, hepatitis, various rashes

  • Ampicillin can cause a maculopapular rash in patients with infectious mononucleosis; this is not a true drug allergy

  • Penicillin allergy can be confirmed with skin testing using major/minor determinants; injections should be done with readiness to treat anaphylaxis

  • Other adverse effects: gut flora disruption, diarrhea, superinfections (e.g., C. difficile colitis) and pseudomembranous colitis

β-Lactamase inhibitors

  • Clavulanic acid: enhances activity of β-lactams by inhibiting β-lactamases; has little antimicrobial effect by itself; only oral inhibitor is clavulanate

    • Effective against H. influenzae, N. gonorrhoeae, E. coli, Salmonella, Shigella, Staph, Klebsiella, Bacteroides fragilis, Legionella

    • Not effective against Enterobacter, Serratia, Morganella, Citrobacter, Pseudomonas, Acinetobacter

  • Sulbactam (with ampicillin; Unasyn)

  • Tazobactam (with piperacillin; Zosyn and with ticarcillin; Timentin)

β-Lactam Drugs: Cephalosporins

  • One of the largest antibiotic groups; four generations (plus later expansions); semisynthetic

  • Generational activity trends:

    • 1st generation: strong activity against Gram-positive cocci; some Gram-negative bacilli

    • 2nd generation: similar Gram-positive activity with increased Gram-negative activity

    • 3rd generation: broader Gram-negative coverage (Enterobacteriaceae, H. influenzae, M. catarrhalis); some cross BBB penetration for meningitis

    • 4th generation (e.g., cefepime): greater Gram-negative resistance to beta-lactamases; better Pseudomonas activity; BBB penetration

    • 5th generation (ceftobiprole, ceftaroline): expanded activity against MRSA and other resistant organisms

  • First-generation examples: Cefadroxil, Cefazolin (IV), Cephalexin, Cephapirin, Cefradine

  • Second-generation examples: Cefaclor, Cefamandole, Cefotetan, Cefoxitin, Cefprozil, Cefuroxime

  • Third-generation examples: Cefdinir, Cefditoren, Cefixime, Cefotaxime, Cefpodoxime, Ceftazidime, Cefizox, Ceftriaxone, Cefoperazone, Ceftibuten

  • Fourth-generation examples: Cefepime, plus related agents crossing BBB and active against Pseudomonas

  • Fifth-generation examples: Ceftobiprole (Zeftera) and Ceftaroline (Teflaro)

  • Cephalosporin coverage notes:

    • 1st gen: good for many streptococci and MSSA; some Enterobacteriaceae

    • 2nd gen: enhanced Gram-negative coverage

    • 3rd gen: meningitis utility; broader Gram-negative activity

    • 4th gen: Pseudomonas coverage; meningitis utility

    • 5th gen: MRSA and broader Gram-positive/negative coverage

β-Lactam Drugs – adverse effects (cephalosporins)

  • Generally excellent safety; lower hypersensitivity incidence than penicillins

  • Cross-sensitivity with penicillins exists; about 5% of people with penicillin allergy may also be allergic to cephalosporins

  • Mild penicillin-allergic patients often tolerate cephalosporins; severe penicillin allergy (anaphylaxis) generally cautioned against cephalosporins

β-Lactam Drugs: Monobactam

  • Aztreonam: a monocyclic β-lactam; active against many aerobic Gram-negative bacilli including Enterobacter, Citrobacter, Klebsiella, Proteus, and Pseudomonas

  • IV formulation for serious infections; limited cross-sensitivity with penicillins/cephalosporins; can be used in penicillin-allergic patients

  • Adverse effects: hypersensitivity and thrombophlebitis

Penicillins, Cephalosporins, Monobactams, Carbapenems: cross-resistance and considerations

  • Cross-sensitivity concerns exist among β-lactam classes; prior severe reaction influences future choices

  • Carbapenems: broad-spectrum β-lactams with activity against Gram-positive, Gram-negative, and anaerobes (except some organisms like Ertapenem for Pseudomonas)

  • Notably effective against ESBL producers; caution with penicillin allergy due to beta-lactam core structure

β-Lactam Drugs: Carbapenems

  • Examples: Imipenem (Primaxin), Meropenem (Merrem), Meropenem/Vaborbactam (Vabomere; carbapenemase inhibitor only), Ertapenem (Invanz), Doripenem (Doribax)

  • Spectrum: broad coverage including Gram-positive, Gram-negative, and anaerobes; Pseudomonas coverage varies (Ertapenem lacks Pseudomonas coverage)

  • Clinical use: IV therapy for a wide range of severe infections (endocarditis, pneumonia, UTI, intra-abdominal, pelvic, skin/soft tissue, etc.); particularly useful for MDR organisms and mixed infections

  • Important caveat: carbapenems can have cross-sensitivity with penicillins and other β-lactams; avoid in patients with significant penicillin allergy

Vancomycin

  • Glycopeptide active against many Gram-positive cocci/bacilli; includes some MRSA strains

  • Used for infections caused by penicillin-resistant organisms when β-lactams are ineffective

  • Also effective for streptococcal and enterococcal infections (including endocarditis and necrotizing fasciitis) caused by penicillin-resistant organisms

  • Additional activity against Bacillus, Clostridium, Corynebacterium

  • Pharmacokinetics: poorly absorbed orally; IV administration for systemic infections; oral vancomycin for C. difficile GI infections

  • Half-life ~6 hours in normal renal function; prolonged in renal failure

  • Adverse effects: potential nephrotoxicity, ototoxicity; red man syndrome if infused too rapidly

Protein Synthesis Inhibitors

  • Prokaryotic ribosomes: 30S and 50S subunits; Eukaryotic ribosomes are 40S/60S, making selective toxicity possible

Aminoglycosides

  • Mechanism: bind 30S, causing misreading of mRNA and incorrect amino acids incorporation; irreversible and bactericidal

  • Drugs: amikacin, gentamicin, neomycin, streptomycin, tobramycin

  • Administration: IV/IM for systemic infections; often used synergistically with β-lactams

  • Spectrum: highly active against aerobic Gram-negative bacilli; used for serious infections and sepsis; limited monotherapy due to resistance and toxicity concerns

  • Uses: severe life-threatening Gram-negative infections, complicated skin/bone/soft tissue infections, complicated UTIs, sepsis, intra-abdominal infections, endocarditis, neonatal sepsis, ocular/topical uses

  • Specific agents: tobramycin (Pseudomonas), gentamicin (E. coli, Klebsiella, Enterobacteriaceae), amikacin (broadest resistance to aminoglycoside-modifying enzymes), kanamycin, streptomycin (TB regimens; some Enterococcus endocarditis synergy)

Tetracyclines

  • Mechanism: bind 30S, block tRNA access to the ribosome, inhibiting amino acid addition; bacteriostatic

  • Derivatives: doxycycline, minocycline, tetracycline; tigecycline is a glycylcycline

  • Pharmacokinetics: chelate divalent/trivalent cations (Ca, Mg, Fe, Zn); avoid with meals containing these ions; dairy reduces oral bioavailability (less effect on doxycycline/minocycline)

  • Spectrum: broad; includes many Gram-positive and Gram-negative organisms, rickettsiae, spirochetes, mycoplasmas, chlamydiae

  • Key uses: Rocky Mountain spotted fever and other Rickettsia infections; Lyme disease and relapsing fever; alternative to macrolides for Mycoplasma pneumoniae; MRSA skin infections (doxycycline/minocycline)

  • Important contraindications: generally contraindicated in children <8 years due to dental/tooth development effects

Macrolides

  • Drugs: erythromycin, azithromycin, clarithromycin

  • Mechanism: bind 50S ribosomal subunit, inhibit translocation during protein synthesis

  • Pharmacology: erythromycin often oral, also IV; azithromycin and clarithromycin typically oral; some indications use IV for severe infections (e.g., Legionella)

  • Spectrum: effective against many Gram-positives and several Gram-negatives; include Chlamydiae, Mycoplasma pneumoniae, Legionella pneumophila; azithromycin useful for sinusitis/otitis media/bronchitis; single-dose therapy for uncomplicated chlamydial urethritis

  • Specific notes:

    • Erythromycin can cause GI prokinetic effects and drug interactions; shorter half-life; azithro/clarithro have longer half-lives and different dosing schedules

    • Clarithromycin is particularly active against Helicobacter pylori

Clindamycin

  • Source: lincomycin derivative

  • Spectrum: active against Gram-positive cocci and anaerobes (Bacteroides fragilis, Clostridium perfringens); effective against MRSA and penicillin-resistant streptococci in some contexts (necrotizing fasciitis)

Linezolid

  • Class: oxazolidinone; synthetic

  • Mechanism: binds 23S rRNA of 50S, prevents formation of the 70S initiation complex

  • Spectrum: aerobic Gram-positives; active against vancomycin-resistant Enterococcus (VRE) and MRSA pneumonia and skin/soft tissue infections

  • Administration: IV or PO

Antifolate Drugs

  • Sulfonamides: historically broad spectrum; now limited primarily for UTIs in combination regimens (e.g., sulfamethoxazole with trimethoprim)

  • Sulfonamide examples: sulfadiazine (topical for burns), sulfacetamide (ocular infections)

  • Adverse effects: hypersensitivity rashes; serious reactions such as erythema multiforme or Stevens-Johnson syndrome; crystalluria, GI upset, hepatitis, hematologic toxicity; hemolytic anemia risk in G6PD deficiency

  • Trimethoprim: active against many Gram-negatives and a few Gram-positives; often used with sulfamethoxazole (TMP-SMX)

  • TMP-SMX (Bactrim, Septra): bactericidal against some Enterobacteriaceae; first-line for Pneumocystis jirovecii (carinii) pneumonia and Nocardia in immunocompromised patients; UTIs

  • Adverse effects: similar to individual drugs; megaloblastic anemia with low folate intake

Fluoroquinolones

  • Mechanism: inhibit bacterial DNA gyrase (topoisomerase II) and Topoisomerase IV, disrupting DNA replication and transcription

  • Pharmacology: usually oral; some agents IV; absorption can be chelated by divalent cations; dosing frequency varies by agent (Cipro and ofloxacin often bid; newer agents like levofloxacin, moxifloxacin are typically once daily)

  • Spectrum: broad activity against Gram-negative bacteria; newer agents also cover many Gram-positives and atypicals; includes activity against Pseudomonas (especially anti-pseudomonal agents)

  • Indications: UTIs, prostatitis, PID, intra-abdominal infections, bone/joint infections, skin infections, pneumonia; traveler's diarrhea; anthrax post-exposure prophylaxis

  • Cautions: contraindicated in children <18 years; can interact with multivitamins and minerals due to chelation; potential tendon rupture risk, QT prolongation concerns in some patients

Nitrofurantoin

  • Mechanism: reduced by bacterial flavoproteins to reactive intermediates that inactivate/damage bacterial ribosomal proteins and other macromolecules

  • Pharmacokinetics: PO, BID; rapidly excreted in urine; activity primarily in the bladder due to limited plasma levels

  • Administration tips: take with food to improve absorption and reduce GI upset

Daptomycin (Cubicin)

  • Mechanism: cyclic lipopeptide; causes rapid membrane depolarization and potassium efflux, halting nucleic acid and protein synthesis, leading to cell death

  • Spectrum: Gram-positive organisms; active against MRSA, some VRE, and some VRSA strains

  • Clinical use: complicated skin/soft tissue infections, foot ulcers, burns

  • Administration and monitoring: IV once daily; monitor creatine phosphokinase (CPK), renal function, and CBC

Antimicrobial drugs contraindicated in pregnancy (mnemonic-linked list)

  • Sulfonamides

  • Aminoglycosides

  • Fluoroquinolones

  • Erythromycin

  • Metronidazole

  • Tetracyclines

  • Ribavirin

  • Griseofulvin

  • Chloramphenicol

  • Note: many guidelines summarize safety with mnemonics; explicit cautions required for pregnancy planning and fetal safety

Antibiotic Coverage by organism groups

  • MSSA (methicillin-susceptible Staph aureus): broad coverage including penicillins, β-lactam/beta-lactamase combinations, cephalosporins, carbapenems, doxycycline, TMP-SMX, clindamycin, vancomycin, linezolid, tetracyclines, etc. (example list)

  • MRSA (methicillin-resistant Staph aureus): limited β-lactam options; cephalomycins (5th gen) may have activity; non-β-lactams like TMP-SMX, clindamycin, doxycycline/minocycline, linezolid, vancomycin, daptomycin, tigecycline, and some ceftaroline activity

  • Pseudomonas: anti-pseudomonal penicillins (piperacillin/tazobactam, ticarcillin/clavulanate), ceftazidime, cefepime, carbapenems (except ertapenem), aztreonam, fluoroquinolones (levofloxacin, ciprofloxacin), aminoglycosides (gentamicin, tobramycin, amikacin)

  • ESBL producers: often resistant to many penicillins and cephalosporins; carbapenems (e.g., imipenem, meropenem, doripenem) are typically effective; ertapenem in some cases limited by lack of Pseudomonas coverage

Dosing guidelines (selected examples)

  • β-lactams:

    • Amoxicillin: 875 mg twice daily

    • Cephalexin: 500 mg three times daily

    • Ceftriaxone: 1 g IV/IM daily

    • Cefdinir: 300 mg twice daily

    • Ertapenem: 1 g IV/IM daily

    • Piperacillin/tazobactam: 3.375 g IV every 6 hours

  • Tetracyclines and fluoroquinolones:

    • Doxycycline: 100 mg twice daily

    • Levofloxacin: 500 mg daily

    • Ciprofloxacin: 500 mg twice daily

  • Other agents:

    • Vancomycin: 1 g IV twice daily

    • TMP-SMX: trimethoprim-sulfamethoxazole DS tablets twice daily

Specific Guidelines by Infection

  • Lyme disease (Borrelia burgdorferi)

    • Tick-borne disease; can cause neurologic (facial palsy), cardiac symptoms, arthritis

    • First-line therapy: oral antibiotics unless hospitalization is required (cardiac conduction issues, severe manifestations)

    • Doxycycline: 100 mg twice daily or 4.4 mg/kg/day in divided doses

    • Pediatric safety: Short course (<21 days) of doxycycline is considered safe for children per CDC, including those under age 8 in certain scenarios; tick-borne diseases are exceptions for tetracycline use in children when benefits outweigh risks

    • Alternatives: Amoxicillin 500 mg three times daily; Cefuroxime or Ceftriaxone also acceptable; treatment duration typically 10–21 days depending on severity

  • Lyme disease prophylaxis after tick bite (PEP)

    • Indication: high incidence area, recent tick bite, tick removed within 72 hours, engorged tick, Ixodes tick identification if possible, safe use of doxycycline for the patient

    • Doxycycline prophylaxis: a single dose of 200 mg (adults) or 4.4 mg/kg (children <45 kg)

    • If any contraindication to doxycycline, PEP not indicated

    • Decision flow: follow local incidence data and risk assessment

  • Rocky Mountain spotted fever (Rickettsia rickettsii)

    • Peak transmission May–August; symptoms: fever, headache, rash, N/V; high suspicion warranted

    • Treatment: doxycycline preferred for at least 5 days (often 7–10 days); 100 mg BID adults or 4.4 mg/kg/day in two divided doses for children; desensitization if allergy

  • Cholera (Vibrio cholerae)

    • Transmission through contaminated water; symptoms include profuse watery diarrhea and vomiting, dehydration

    • Management: aggressive rehydration; antibiotics as adjunctive therapy

    • First-line antibiotic: doxycycline (single-dose regimen)

    • Alternatives: azithromycin or ciprofloxacin depending on allergy or local resistance

  • Diphtheria (Corynebacterium diphtheriae)

    • Respiratory disease from toxin-producing strains; symptoms mild at onset but can progress

    • Treatment: erythromycin or penicillin

Notes on practical concepts

  • Commensals and host interactions are essential for health, but can become opportunistic pathogens when host defenses are compromised

  • The rise of multidrug-resistant organisms (MDROs) such as ESBL producers and MRSA necessitates careful antibiotic selection and stewardship

  • For severe infections, bactericidal agents are often preferred to ensure rapid bacterial kill

  • Understanding MIC, MBC, and the pharmacodynamics/pharmacokinetics (time- vs concentration-dependent killing) helps optimize therapy

  • Antibiotic safety in special populations (pregnancy and pediatrics) requires attention to drug-specific contraindications and safety profiles

Key LaTeX-formatted concepts (for exam clarity)

  • MIC: extMinimuminhibitoryconcentration(MIC)ext{Minimum inhibitory concentration (MIC)}

  • MBC: extMinimumbactericidalconcentration(MBC)ext{Minimum bactericidal concentration (MBC)}

  • Time above MIC: C(t) > MIC ext{ for a significant fraction of the dosing interval}

  • Post-antibiotic effect: extPAEext{PAE}

  • PBP: extPenicillin−bindingproteins(PBPs)ext{Penicillin-binding proteins (PBPs)}

  • β-lactamase: extEnzymesthathydrolyzetheβ−lactamringext{Enzymes that hydrolyze the β-lactam ring}

  • ESBL: extExtended−spectrumβ−lactamasesext{Extended-spectrum β-lactamases}

  • KPC: extKlebsiellapneumoniaecarbapenemaseext{Klebsiella pneumoniae carbapenemase}

  • LPS: extLipopolysaccharide(endotoxin)inGram−negativebacteriaext{Lipopolysaccharide (endotoxin) in Gram-negative bacteria}

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