Clinical beta

FMBM is currently in clinical beta. Content is for professional review/testing and must not replace local protocols, senior clinical judgment, or official prescribing references.

Drug Monograph

Trimethoprim-Sulfamethoxazole

Trimethoprim–sulfamethoxazole

Folate pathway inhibitor combination (PO, IV)

MRSAPJPUTIHyperkalemia

Indication

CA-MRSA β€’ UTI β€’ PJP β€’ toxoplasma β€’ Nocardia selected

At a glance

INDICATIONS (CORE USE)

MRSA SSTI/UTI; **PJP** treatment/prophylaxis; **hyperkalemia** especially high-dose IV + CKD + ACEi; **SJS/TEN** class risk.

ADULT DOSE (STANDARD)

DS tablet BID (many infections); PJP 15–20 mg/kg/day TMP component IV divided β€” **distinct**

MAX DOSE

PJP dosing is high β€” monitor K+, creatinine, CBC

Route

PO, IV

PEDIATRIC DOSE

8–12 mg/kg/day TMP component divided BID UTI; PJP higher β€” specialist

Do not miss

Must-not-miss safety points

Major warning

- **Hyperkalemia** β€” TMP like amiloride; worse with ACEi/ARB/spironolactone/CKD - **Stevens-Johnson / TEN** β€” counsel rash/fever/mucosa - **Bone marrow suppression** high-dose / HIV - Folate antagonism β€” avoid in first trimester relative; G6PD hemolysis sulfonamide component

Indications

USE IF: MRSA SSTI, UTI when susceptible, PJP HIV/oncology. AVOID IF: Critical hyperkalemia risk stack; sulfa anaphylaxis; first trimester relative.

Primary

  • Uncomplicated UTI (resistance-dependent) and some pyelonephritis oral
  • CA-MRSA skin infection oral/IV
  • Pneumocystis jirovecii pneumonia treatment and prophylaxis

Secondary

  • Toxoplasma prophylaxis HIV
  • Nocardia (specialist high-dose regimens)

Other

  • Stenotrophomonas maltophilia regimens β€” specialist

Dosing

STANDARD (ADULT PO)

1 DS PO BID (many SSTI/UTI) vs TMP 15–20 mg/kg/day IV divided (PJP) β€” **different regimens**

ADULT DOSE

1 DS PO BID many SSTI/UTI PJP treatment: TMP 15–20 mg/kg/day + sulfa component paired IV divided q6–8h β€” **not DS tablet math**

PEDIATRIC DOSE

TMP mg/kg component dosing β€” always specify component.

MAX DOSE

PJP doses β€” monitor labs aggressively.

Practical Note

CrCl <30 β†’ adjust or avoid depending on indication per label.

Warnings

Clinical warnings

  • Crystalluria β€” hydration
  • Hepatitis

Adverse effects

  • rash
  • hyperkalemia
  • AKI
  • myelosuppression

Contraindications

  • Sulfonamide anaphylaxis
  • Infants <2 months (kernicterus risk historical)

Drug interactions

  • ACEi/ARB/spironolactone β€” K+
  • Warfarin β€” INR
  • Methotrexate β€” toxicity

Special populations

Pediatrics

8–12 mg/kg/day TMP component divided BID UTI; PJP higher β€” specialist

Pregnancy

Avoid first trimester if possible

Lactation

generally compatible term infant; kernicterus sulfonamide neonate theoretical.

Renal impairment

Reduce dose CKD; HD dosing; K+ monitoring. **CrCl scaffold (FMBM β€” titrate to FDA/SFDA label + institutional pharmacy nomogram):** - **CrCl β‰₯50** β†’ standard DS dosing many indications (verify indication-specific tables) - **CrCl 10–50** β†’ ↓ dose or extend interval per label; **K+ surveillance** if ACEi/ARB/spironolactone - **CrCl <10** / **HD** β†’ avoid or high-caution; PJP high-dose **protocol only**; **K+** monitoring

Hepatic impairment

Severe hepatic impairment β€” caution sulfonamide accumulation.

Elderly

K+ + AKI + polypharmacy.

Administration

PO with fluids; IV infusion time per product.

Monitoring

  • Monitor: - ACEi / ARB / spironolactone / CKD stack β†’ **BMP (K+, creatinine)** - High-dose PJP or prolonged course β†’ **CBC** - Rash + fever / mucosal involvement β†’ **stop** β†’ evaluate **SJS/TEN** - BMP 2–3Γ—/week inpatient high-dose PJP - CBC weekly high-dose - K+ day 3–5 outpatient SSTI if on ACEi
  • Recheck: - No clinical improvement at 48–72h β†’ reassess diagnosis, resistance, source control, and drug interactions - If targets not met after reassessment of dose, organ function, and interactions β†’ escalate per protocol (DO NOT continue blindly)

Overdose / toxicity

Clinical Picture

**Life-threatening (first):** **hyperkalemia** with **ECG instability**; **SJS/TEN**; **pancytopenia** with sepsis. **Secondary:** AKI (TMP effect); rash.

Immediate Actions

Stop β†’ BMP, CBC, ECG if K+ concern; fluids; calcium/insulin-glucose if severe hyperK+

Antidote

No specific antidote; treat complications (e.g. hyperkalemia per protocol, anaphylaxis β†’ epinephrine, SJS/TEN β†’ burn/ICU pathway)

Decontamination

Recent PO β†’ charcoal if appropriate

Escalation

SJS/TEN, severe hyperK+ with ECG changes, pancytopenia with sepsis β†’ **ICU** / burn; **AKI β†’ HD** if indicated β€” TMP clearance partially enhanced

Clinical pearls

Common mistakes, resistance logic, and bedside traps

High-Yield Summary

**MRSA + PJP** Swiss army knife. **K+** climbs silently with ACEi + CKD. **PJP dose** is not β€œ1 DS BID.”

Clinical pearls

Stewardship: UTI resistance varies β€” culture first recurrent UTIs. PJP prophylaxis indications HIV/oncology β€” don’t miss transplant thresholds. Folate not routine for short UTI but consider HIV malnutrition prolonged therapy. *Stewardship (all antimicrobials):* Empiric choice β†’ syndrome severity + **local antibiogram**; shortest effective course.

Stewardship & safety

  • K+ monitoring
  • SJS vigilance
  • PJP mg/kg TMP

Pharmacokinetics

Renal elimination; penetrates lung for PJP; CSF in inflamed meninges moderate.

Mechanism of action

Sequential folate inhibition β€” TMP + SMX synergistic.

Common brand names

Global data (no country-specific data available)

Saudi Arabia

(placeholder β€” verify local formulary)

Common trade names are curated examples only β€” formulations and availability vary. Verify the exact product name with your local pharmacy and national regulator before prescribing or dispensing.

Country practice notes

  • Empiric choice β†’ tie to syndrome, severity, and local antibiogram β€” not habit.
  • IV β†’ PO step-down when oral bioavailability and susceptibility allow.
  • Do not use antibiotics for uncomplicated viral illness β€” stewardship.

References

Saudi Arabia

  • SFDA (Saudi Food & Drug Authority)
  • Saudi National Formulary / MOH (where available)

International

  • WHO Model List of Essential Medicines (verify current edition)
  • US FDA or EU EMA product information (when national SmPC is unavailable)
  • Sanford Guide
  • IDSA / ESCMID (indication-specific)
  • Local antimicrobial stewardship / hospital formulary
  • FDA / SFDA / regional product labeling
  • Sanford Guide
  • IDSA / ESCMID (indication-specific)
  • Local antimicrobial stewardship / hospital formulary
  • FDA / SFDA / regional product labeling

Do not miss

  • Uncomplicated viral URI/bronchitis β†’ antibiotics rarely indicated
  • Narrow or stop when susceptibilities + clinical stability allow
  • Hyperkalemic arrest in CKD on TMP-SMX + spironolactone.
  • SJS β€” stop at first mucosal involvement.
  • K+ monitoring
  • SJS vigilance
  • PJP mg/kg TMP