a) Physiologic and immunologic changes in pregnancy predisposing to infection [5]

1. Altered cell-mediated immunity
   • To tolerate the semi-allogeneic fetus, there is relative suppression of Th1-type, cell-mediated immunity with relative predominance of humoral/Th2 responses.
   • This reduces control of intracellular pathogens and increases severity or dissemination of some viral, fungal, and intracellular bacterial infections, such as influenza, varicella, listeriosis, and coccidioidomycosis. This is a regulated immune adaptation, not complete immunosuppression.
2. Respiratory changes
   • Elevation of diaphragm, reduced functional residual capacity, and increased oxygen consumption reduce respiratory reserve.
   • Thus pneumonia or influenza can cause hypoxemia and respiratory failure more rapidly.
3. Urinary tract dilatation and stasis
   • Progesterone relaxes ureteric smooth muscle; the gravid uterus compresses the ureters.
   • Hydroureter, hydronephrosis, vesicoureteric reflux, and urinary stasis promote bacteriuria and ascending UTI/pyelonephritis, particularly in the second and third trimesters.
4. Genital tract changes
   • Increased estrogen increases vaginal glycogen and alters vaginal flora/pH, favoring Candida colonization and vulvovaginitis.
   • Increased cervical secretions and pelvic vascularity may also facilitate local infection.
5. Other systemic changes
   • Increased plasma volume and altered renal/hepatic drug handling can lower effective antimicrobial concentrations if dosing is not adjusted.
   • Changes in skin, mucosal barriers, glucose metabolism, and nutritional demands may further increase infection risk in susceptible women.

b) General principles of antimicrobial use and contraindicated drugs in pregnancy [5]

General principles

1. Treat significant maternal infection promptly. Untreated infection can be more dangerous to both mother and fetus than an appropriately selected antimicrobial.
2. Confirm infection where possible. Obtain appropriate cultures before therapy if this does not delay treatment; then use sensitivity results to narrow treatment.
3. Use the safest effective agent.
   • Prefer agents with established pregnancy safety data, especially penicillins, cephalosporins, and azithromycin/clindamycin when clinically appropriate.
   • Use the narrowest effective spectrum, correct dose, and shortest effective duration.
4. Consider gestational age and fetal effects.
   • Risks differ in the first trimester, when organogenesis occurs, and near delivery, when neonatal toxicity may occur.
   • Consider placental transfer, fetal toxicity, maternal allergy, renal/hepatic function, infection severity, and local resistance pattern.
5. Adjust for pregnancy pharmacokinetics.
   • Increased plasma volume, increased glomerular filtration, and altered protein binding may reduce serum drug concentrations, so standard doses may sometimes be inadequate. Monitor clinical response and drug levels when applicable.

Drugs generally avoided or contraindicated