Do corticosteroids impair the effectiveness of antibiotics?

Do Corticosteroids Impair Antibiotic Effectiveness?

Corticosteroids do not directly impair antibiotic effectiveness, but they increase infection risk through immunosuppression and can worsen outcomes if antibiotics are inadequate or if timing is inappropriate. 1, 2

Key Mechanism: Immunosuppression, Not Antibiotic Antagonism

• Corticosteroids suppress the immune system by inducing defects in lymphocyte signaling and reducing inflammatory cell activation, which enhances infection susceptibility rather than blocking antibiotic action 1, 2
• The FDA warns that corticosteroids reduce resistance to new infections, can exacerbate existing infections, increase risk of disseminated infections, and mask signs of infection 2
• Corticosteroids inhibit activation and infiltration of inflammatory cells (macrophages and polymorphonuclear leukocytes) that are essential in the first phase of wound healing and infection control 3

Critical Timing Considerations

• When corticosteroids are given BEFORE adequate antibiotic therapy is established, mortality increases significantly 4
• In animal models of gram-negative bacterial infections, administering corticosteroids prior to antibiotics increased mortality compared to antibiotics alone, while giving corticosteroids after starting antibiotics reduced mortality 4
• For bacterial keratitis, adding topical corticosteroids within 2-3 days of antibiotic therapy (rather than after 4+ days) resulted in better visual outcomes, demonstrating that early concurrent use with antibiotics can be safe 3

When Corticosteroids Are Safe With Antibiotics

The safety of corticosteroids depends entirely on whether the antimicrobial can effectively clear or suppress the infection 5

• For bacterial meningitis, tuberculous meningitis, tuberculous pericarditis, severe typhoid fever, and Pneumocystis pneumonia with moderate-to-severe hypoxemia, corticosteroids with appropriate antibiotics improved patient survival 6
• In bacterial keratitis, the SCUT trial found no increase in adverse events when topical corticosteroids were used with broad-spectrum topical antibiotics, though overall benefit was not conclusively demonstrated 3, 5
• Corticosteroids should only be added after at least 2-3 days of progressive improvement with antibiotic treatment and after pathogen identification 3

Specific Pathogens Where Corticosteroids Are Harmful

• Nocardia infections: Treatment with corticosteroids resulted in poor visual outcomes in bacterial keratitis 3
• Fungal infections: Corticosteroids may exacerbate systemic fungal infections and should be avoided unless needed to control drug reactions 2, 5, 7
• Acanthamoeba keratitis: Observational studies found steroids harmful when started prior to anti-amoebics 5
• Viral hepatitis and cerebral malaria: Corticosteroids were directly harmful in these infections 6

Practical Algorithm for Concurrent Use

Before initiating corticosteroids in patients on antibiotics:

• Screen carefully for infection and ensure any baseline infection is well-treated and "controlled" before starting steroids 1
• Rule out fungal infection, Nocardia, latent tuberculosis, strongyloides, and amebiasis 2
• Screen for hepatitis B infection before immunosuppressive treatment, as reactivation can occur 2

During concurrent therapy:

• Continue monitoring for new infections during treatment and follow-up 1
• In patients with baseline infection receiving corticosteroids, continued antibiotic therapy reduced mortality from 52% to 13% 1
• Use the minimum corticosteroid dose required to achieve the desired clinical effect 3, 1
• Monitor intraocular pressure if using corticosteroids near the eye 3

Dose and duration thresholds for infection risk:

• Significant infection risk occurs with >30 mg prednisone-equivalent dose for >4 weeks, or ≥15 to <30 mg for ≥8 weeks 8
• The infectious complication rate increases with increasing corticosteroid dosages 2
• Consider antimicrobial prophylaxis (tuberculosis, hepatitis B, Strongyloides, Pneumocystis jirovecii) in high-dose or prolonged therapy 8

Common Pitfalls to Avoid

• Never start corticosteroids before establishing adequate antibiotic coverage - this increases mortality in bacterial infections 4
• Do not use corticosteroids in presumed bacterial infections until the organism is identified and the infection is responding to antibiotics 1
• Discontinue or reduce corticosteroids during active infection episodes 1, 8
• Avoid periocular corticosteroid injections without ophthalmology consultation due to vision-threatening complications 9
• Do not assume corticosteroids will "help" inflammation in all infections - they worsen outcomes in fungal, Nocardia, and certain viral infections 3, 2, 6

Special Surgical Considerations

• In surgical patients, corticosteroids significantly increase risk of anastomotic leakage, wound infection, and wound dehiscence by impairing wound healing 3
• Corticosteroids inhibit collagen synthesis, which predisposes to corneal melting in ocular infections and impairs surgical wound healing 3
• Long-term or perioperative corticosteroid use increases gastrointestinal bleeding, peptic ulcer perforation, and sigmoid diverticular perforation risk 3