Lecture 3&4

The ability of bacteria to survive exposure to antibiotics that would normally kill them or inhibit their growth. Resistance mechanisms include enzyme production (beta-lactamases, carbapenemases), efflux pumps, porin loss, and target modification. CDC estimates over 2.8 million resistant infections and more than 35,000 deaths per year in the United States (2019 data). COVID-19 reversed progress: hospital-onset resistant infections increased 20% during 2020–2022.

Bacteria with a thick peptidoglycan cell wall and no outer membrane. Retain crystal violet stain (appear purple). The thick peptidoglycan layer is the target for beta-lactam antibiotics and vancomycin. Examples in this lecture: Clostridioides difficile, MRSA, VRE, Streptococcus pneumoniae.

Bacteria with a thin peptidoglycan layer and an outer membrane containing lipopolysaccharide (LPS). The outer membrane acts as a permeability barrier, making Gram-negative organisms inherently harder to treat. Examples in this lecture: Acinetobacter baumannii, Enterobacterales (E. coli, Klebsiella), Neisseria gonorrhoeae.

A polymer of sugars and amino acids that forms the bacterial cell wall. Essential for structural integrity — bacteria that cannot synthesize peptidoglycan die. Target of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems) and vancomycin. The peptidoglycan biosynthesis pathway is the basis for the largest class of antibiotics in clinical use.

A component of the outer membrane of Gram-negative bacteria. The Lipid A portion is endotoxin: when Gram-negative bacteria lyse, LPS is released and triggers an inflammatory cascade that can lead to septic shock. Relevant to pharmacy: parenteral drug manufacturing requires endotoxin testing (LAL test) to prevent pyrogenic reactions

Bacterial enzymes involved in peptidoglycan biosynthesis. The molecular target of all beta-lactam antibiotics. Beta-lactams bind PBPs and block cell wall cross-linking, leading to bacterial lysis and death.

The largest class of antibiotics, sharing a beta-lactam ring that binds penicillin-binding proteins (PBPs). Includes penicillins, cephalosporins, and carbapenems. Mechanism: block peptidoglycan cross-linking. Resistance occurs through beta-lactamase enzymes that hydrolyze the beta-lactam ring.

The broadest-spectrum beta-lactam antibiotics (imipenem, meropenem, ertapenem). Resist most beta-lactamases that destroy penicillins and cephalosporins. Reserved for severe or resistant infections where other beta-lactams have failed. When carbapenems fail, the result is CRE — a CDC urgent
threat.

An enzyme produced by bacteria that breaks the carbapenem ring, rendering carbapenems ineffective. The three major types are KPC (Klebsiella pneumoniae carbapenemase), NDM (New Delhi metallo-beta-lactamase), and OXA-48. These enzymes spread on plasmids between bacterial species. Identifying the carbapenemase type determines the treatment: KPC responds to ceftazidime-avibactam; NDM has very limited options (cefiderocol, aztreonam-avibactam)

The most common carbapenemase in the United States. Confers resistance to carbapenems. Treatable with newer beta-lactameta-lactamase inhibitor combinations: ceftazidime-avibactam (first-line), meropenem-vaborbactam, or imipenem-relebactam.

A metallo-beta-lactamase that uses zinc to hydrolyze the carbapenem ring. Surged 460% from 2019 to 2023. Resists nearly all antibiotics including most new beta-lactameta-lactamase inhibitor combinations. Treatment options are limited to cefiderocol or aztreonam combined with avibactam.

Enterobacterales (E. coli, Klebsiella, Enterobacter, and others) that are resistant to carbapenems, the last-line beta-lactam antibiotics. CDC URGENT THREAT. Up to 50% mortality in bloodstream infections. Baseline (2019): 9,000 infections and 600 deaths per year; during COVID: 12,700 infections and over 1,100 deaths. Treatment depends on identifying the carbapenemase type (KPC vs. NDM). Pan-resistant CRE (zero effective drugs) have been reported.

A polymyxin antibiotic discovered in 1949 and abandoned for decades due to nephrotoxicity and neurotoxicity. Brought back as a last resort for multidrug-resistant Gram-negative infections, particularly Acinetobacter baumannii and some CRE. Requires therapeutic drug monitoring (TDM) and renal dose adjustment. Colistin-resistant strains represent truly untreatable infections.

CDC classification system for antibiotic-resistant organisms based on seven factors: clinical impact, economic impact, incidence, ten-year projection, transmissibility, availability of effective antibiotics, and barriers to prevention. Five urgent threats: carbapenem-resistant Acinetobacter, CRE, Clostridioides difficile, drug-resistant Neisseria gonorrhoeae, and Candida auris. Factors 6 (drug availability) and 7 (prevention barriers) are directly influenced by pharmacists

A coordinated program to optimize antibiotic use: right drug, right dose, right duration. Goals: improve patient outcomes, reduce resistance, and minimize adverse effects including C. difficile. Pharmacist responsibilities include prospective audit and feedback, de-escalation when cultures return, reviewing every antibiotic order for indication, and flagging unnecessary fluoroquinolone or clindamycin use. CDC estimates 47 million (30%) of outpatient antibiotic prescriptions in the United States are unnecessary.

First-in-class spiropyrimidinetrione antibiotic. FDA-approved December 2025 for uncomplicated urogenital gonorrhea. Targets bacterial DNA gyrase at a different subunit than fluoroquinolones. Administered as a single oral dose (granules dissolved in water). Approved only for gonorrhea. One of the first new antibiotic classes for gonorrhea in over 30 years.

Novel triazaacenaphthylene antibiotic. FDA-approved December 2025. Dual-target mechanism: inhibits both bacterial DNA gyrase and topoisomerase IV. Oral tablets (8 pills in two doses). Approved for both uncomplicated gonorrhea and urinary tract infections

Staphylococcus aureus resistant to methicillin and other beta-lactam antibiotics due to acquisition of the mecA gene encoding an altered PBP (PBP2a). CDC SERIOUS THREAT. Treatment: vancomycin, daptomycin, linezolid, trimethoprim-sulfamethoxazole (community strains). Covered in Weeks 5–6 with Dr. Mahmud.

Enterococcus faecium or E. faecalis resistant to vancomycin,the drug normally reserved for serious Gram-positive infections. CDC SERIOUS THREAT. Treatment options include linezolid and daptomycin. Covered in Week 6 (peptide antibiotics).

An enzyme produced by certain Enterobacterales (especially E. coli and Klebsiella) that confers resistance to most beta-lactam antibiotics including third-generation cephalosporins. CDC SERIOUS THREAT. Treatment: carbapenems (stewardship: confirm ESBL before committing). Nitrofurantoin is often still active for uncomplicated urinary tract infections — a stewardship opportunity to avoid carbapenem use. Rising in community-onset urinary tract infections

The causative agent of whooping cough. On the CDC watch list for emerging drug resistance. Pharmacists administer the Tdap vaccine, which is the primary prevention strategy. Drug-resistant strains make vaccination even more critical — resistance is a prevention argument for immunization

An emerging sexually transmitted infection on the CDC watch list. Rising azithromycin resistance. Current treatment fallback: moxifloxacin (a fluoroquinolone). Another STI losing treatment options, alongside gonorrhea

Gram-negative bacillus. CDC URGENT THREAT (carbapenem-resistant strains). Primarily an ICU pathogen: causes pneumonia, bloodstream infections, meningitis, and urinary tract infections. Survives weeks on dry hospital surfaces. Multidrug-resistant strains may be susceptible only to colistin. Sulbactam has unusual intrinsic activity against Acinetobacter — ampicillin-sulbactam is sometimes an option. Cycle of spread: contaminated surfaces → healthcare worker hands → vulnerable patient → surfaces. Breaking this cycle requires hand hygiene, surface cleaning, contact precautions, and stewardship simultaneously.

A large order of Gram-negative bacteria that includes E. coli, Klebsiella, Enterobacter, Citrobacter, and Serratia. Normal gut flora that cause serious infections when they escape the gastrointestinal tract. The family from which CRE (Carbapenem-Resistant Enterobacterales) and ESBL-producing strains arise.

A beta-lactameta-lactamase inhibitor combination. First-line treatment for KPC-producing CRE. Avibactam inhibits KPC and OXA-48 carbapenemases (but not NDM metallo-beta-lactamases). Covered in Week 6 with Dr. Mahmud.

A siderophore cephalosporin with a unique mechanism: uses bacterial iron transport systems to enter the cell (a “Trojan horse” strategy). Active against NDM-producing CRE and broadly against difficult-to-treat Gram-negative organisms. One of very few options for NDM infections.

Gram-negative, encapsulated, non-motile bacterium. The #1 CRE species and the #1 cause of hospital-acquired pneumonia in the United States. Accounts for 3–8% of all nosocomial bacterial infections. Colonizes oropharynx and GI tract; spreads by person-to-person contact. Emerging threat: hypervirulent K1/K2 capsule strains cause liver abscess in otherwise healthy patients and can be simultaneously carbapenem-resistant.

A periodic summary of antimicrobial susceptibility testing results for bacterial isolates at a given institution. Used to guide empiric antibiotic therapy before culture results are available. Pharmacist responsibility: maintain, interpret, and use the antibiogram. If local antibiogram shows >10% carbapenem resistance in Klebsiella, suspect CRE and escalate to infectious disease consult.

The most common Gram-negative facultative anaerobe in the human GI tract. Multiple pathotypes: UPEC (uropathogenic, causes ~80% of uncomplicated UTIs), ETEC (enterotoxigenic, #1 cause of traveler’s diarrhea), EHEC (enterohemorrhagic, produces Shiga toxin). Also the #1 cause of Gram-negative bacteremia (urosepsis). ESBL- producing E. coli is a CDC serious threat. In Oregon, pharmacists can prescribe for uncomplicated UTIs — knowledge of E. coli resistance patterns is essential.

Nitrofurantoin 100 mg twice daily for 5 days (avoid if CrCl <30 mL/min). Trimethoprim-sulfamethoxazole (TMP-SMX) DS twice daily for 3 days (only if local resistance <20%). Fosfomycin 3 g single dose (convenient but less effective). Fluoroquinolones: reserve for complicated UTI or pyelonephritis only — stewardship principle.

E. coli pathotype that produces Shiga toxin. Causes bloody diarrhea; sources include undercooked beef, raw milk, spinach, and contaminated water. Approximately 10% of infected children develop hemolytic uremic syndrome (HUS). CRITICAL RULE: suspected EHEC = NO antibiotics (antibiotics lyse bacteria → massive Shiga toxin release → increased HUS risk) and NO antimotility agents (loperamide). Supportive care only. This rule applies to all bloody diarrhea of unknown etiology until EHEC is ruled out.

A triad of hemolytic anemia (red blood cell destruction), acute kidney failure (uremia), and thrombocytopenia (low platelets). Occurs in ~10% of EHEC-infected children. Death rate: 3–5%, mainly children. Triggered by Shiga toxin. Antibiotic use in EHEC increases HUS risk — this is why stopping the antibiotic is the correct pharmacist intervention.

Gram-negative enteric pathogen. Estimated 1.2 million illnesses per year in the United States. Causes diarrhea, fever, and abdominal cramps (onset 12–72 hours). Sources: poultry, eggs, reptile pets, contaminated produce. TREATMENT RULE: most Salmonella gastroenteritis gets NO antibiotics — self-limited illness; antibiotics can prolong fecal shedding. Treat ONLY if: invasive disease (bacteremia), immunocompromised, age <12 months, age >50 with atherosclerosis, or prosthetic devices. Pharmacists administer typhoid vaccine for travelers

Gram-negative enteric pathogen. CDC SERIOUS THREAT (drug-resistant strains). Highly contagious: infectious dose only 10–100 organisms. Causes bloody diarrhea, tenesmus, fever. Unlike Salmonella, Shigella DOES benefit from antibiotics (shortens illness, reduces transmission). But resistance is rising: extensively drug-resistant Shigella (resistant to azithromycin, fluoroquinolones, TMP-SMX, and ampicillin) has been reported, sometimes requiring carbapenems for a GI infection.

Three enteric pathogens, three different antibiotic decisions. Salmonella: usually NO antibiotics (self-limited). Shigella: YES antibiotics (check resistance first). EHEC: NEVER antibiotics (HUS risk). This distinction is a high-value pharmacist knowledge point.

Gram-positive, spore-forming anaerobic bacterium. CDC URGENT THREAT. Not resistant to its treatment drugs — directly CAUSED by antibiotic use. Secretes toxins A and B that damage intestinal lining. Spectrum: asymptomatic carriage → diarrhea → pseudomembranous colitis → toxic megacolon. 250,000 illnesses, 14,000 deaths, $1 billion excess costs per year. 15–35% recurrence rate. Worst offender antibiotics: fluoroquinolones (highest risk), clindamycin, broad-spectrum cephalosporins. PPIs increase risk. Hand hygiene: soap and water, NOT alcohol gel (alcohol does not kill spores).

First-line: oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days (lower recurrence rate). Recurrence prevention: bezlotoxumab (monoclonal antibody against Toxin B). Multiple recurrences: fecal microbiota transplantation or FDA-approved live biotherapeutic products (Vowst, Rebyota). CRITICAL: metronidazole is NO LONGER first-line. Use ORAL vancomycin, not intravenous — IV vancomycin does not reach the colon at therapeutic concentrations.

A macrocyclic antibiotic used for C. difficile infection. Narrow-spectrum: targets C. difficile with minimal disruption to normal gut flora. Lower recurrence rate compared to vancomycin. First-line option per 2021 IDSA guidelines

A monoclonal antibody directed against C. difficile Toxin B. Used alongside standard antibiotic therapy to prevent recurrence of C. difficile infection. Administered intravenously as a single dose.

Gram-negative bacterium causing gonorrhea, a sexually transmitted infection. CDC URGENT THREAT (drug-resistant strains). Estimated 1.6 million cases per year in the United States; 82–87 million globally. Consequences: pelvic inflammatory disease, infertility (both sexes), ectopic pregnancy, neonatal blindness, increased HIV transmission. Every antibiotic class deployed against it has encountered resistance. No vaccine exists.

Ceftriaxone 500 mg intramuscular, single dose (standard of care). NEW (December 2025): zoliflodacin (Nuzolvence) and gepotidacin (Blujepa) are the first new oral treatment classes in over 30 years. Do NOT use oral cephalosporins or fluoroquinolones (>30% resistance). Ensure test-of-cure for pharyngeal gonorrhea. Participate in expedited partner therapy where state law permits

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