Empiric antibiotic therapy is the initial treatment given before a specific pathogen is identified, and it’s critical for managing life-threatening infections. This guide summarizes empiric treatment strategies for most clinically important baterias and common infectious diseases.
MRSA vs MSSA vs VISA vs VRSA
Methicillin-resistant Staphylococcus aureus (MRSA) is a global concern in both hospital and community settings. Methicillin is is anti staphilococcal penicillin like Oxacillin, Nafcillin and Dicloxacillin, however Methicillin is no longer in clinical use due to nephrotoxicity, but resistance is defined relative to it.
- Resistance Mechanism: MRSA acquires the mecA gene via horizontal gene transfer. This encodes penicillin-binding protein PBP2a, reducing affinity for beta-lactam antibiotics.
- MSSA: Oxacillin MIC ≤ 2 µg/mL
- MRSA: Oxacillin MIC ≥ 4 µg/mL
Treatment of MSSA:
- Anti-staphylococcal penicillins: Oxacillin, Nafcillin, Dicloxacillin
- Cephalosporins: Cefazolin, Cephalexin
Treatment of MRSA:
- First-line: Vancomycin, Daptomycin
- Alternatives: Linezolid, Tedizolid, Clindamycin, TMP-SMX, Doxycycline, Delafloxacin, Ceftaroline, Ceftobiprole
Note: Ceftaroline is a fifth-generation cephalosporin with unique structure, effective against both MRSA (via PBP2a binding) and penicillin-resistant Streptococcus pneumoniae (via PBP2x binding).
Vancomycin Resistance: VISA, VRSA, and VRE:
- VISA (Vancomycin-intermediate S. aureus): has partial (intermediate) susceptibility to Vancomycin.
- VRSA (Vancomycin-Resistant S. aureus): Complete resistance via vanA gene from vancomycin-resistant Enterococcus (VRE)
Treatment of VISA and VRSA:
- Daptomycin, Linezolid, Tedizolid, Ceftaroline, Quinupristin-Dalfopristin
Vancomycin-resistant Enterococcus (VRE) treatment:
- Linezolid, Daptomycin, Quinupristin-Dalfopristin, Tigecycline, Omadacycline, Eravacycline
Empiric Therapy for Sexually Transmitted Infections (STIs)
- Neisseria gonorrhoeae: Ceftriaxone (single dose)
- Chlamydia trachomatis: Doxycycline
- Trichomonas vaginalis: Metronidazole (single dose for patient and partner)
- Gardnerella vaginalis (bacterial vaginosis): Metronidazole (1st line) or Clindamycin
- Treponema pallidum (Syphilis): single intramuscular dose of benzathine Penicillin G or Doxycycline as alternative for nonpregnant, penicillin-allergic patients.
Urinary Tract Infections (UTIs)
Common pathogens: Escherichia coli (~75%), Proteus mirabilis, Klebsiella spp., Enterococcus spp.
Uncomplicated UTI: (infection is limited to lower urinary tract, for example a simple cystitis in patient with no other medical condition)
- Nitrofurantoin, Fosfomycin, TMP-SMX
Complicated UTI or Pyelonephritis: (Complicated UTI means when there is urinary tract infection in pregnancy, anatomical abnormalities or infection spreads and/or pyelonephritis develop)
- Ceftriaxone, Ciprofloxacin
Gastrointestinal Infections
Clostridioides difficile produces Toxin A and B that damage enterocytes and cause watery diarrhea, pseudomembranous colitis and/or toxic megacolon.
- Treatment: Oral Vancomycin or Fidaxomicin are first-line treatments, Metronidazole is reserved for mild cases or resource-limited settings.
Intra-abdominal Infections
Common pathogens: E. coli, Bacteroides fragilis, Enterococcus spp, anaerobes.
- Mild or Moderate: Ceftriaxone + Metronidazole
- Severe or Perforated: Piperacillin-tazobactam or Meropenem
Vector-Borne Infections
Lyme disease is caused by Borrelia burgdorferi. Globally, the disease is referred to as borreliosis, but it was named Lyme disease after the town of Lyme, Connecticut, where it was first recognized.
- Borrelia burgdorferi:
- Early localized: Doxycycline
- Disseminated (e.g., neurologic or cardiac involvement): IV Ceftriaxone
Respiratory Tract Infections
Community-Acquired Pneumonia (CAP) can be caused by following bacterias:
- “Typical”: Streptococcus pneumoniae, Haemophilus influenzae
- “Atypical”: Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp.
Beta-lactam antibiotics exert their antibacterial effect by inhibiting peptidoglycan synthesis in the bacterial cell wall. Atypical bacteria lack a peptidoglycan cell wall, and therefore, beta-lactam antibiotics are ineffective against them.
For Outpatients: Amoxicillin-clavulanate for typical bacterias + either Azithromycin (preferred) or Doxycycline for atypical coverage. Azithromycin is preferred in pneumonia treatment because it achieves exceptionally high concentrations in lung tissue—up to 10 to 100 times higher than in plasma—due to its excellent pulmonary penetration and high cellular uptake, particularly by phagocytic cells. This pharmacokinetic profile makes it a key component of empiric pneumonia therapy.
For inpatients (non-ICU): combination with Ceftriaxone + Azithromycin or Levofloxacin monotherapy (Fluoroquinolones can cover both “typical” and “atypical” bacterias.)
Note: Avoid macrolides and fluoroquinolones in patients with prolonged QTc interval; use Doxycycline + Cephalosporin instead as they do not further prolong QTc interval.
Hospital or Ventilator-Acquired Pneumonia (HAP / VAP) can be caused by following pathogens: Pseudomonas aeruginosa, MRSA, Klebsiella spp., Acinetobacter baumannii, Enterobacter, E. coli.
- Treatment: Piperacillin-tazobactam or Cefepime to cover Pseudomonas, Klebsiella, Enterobacter and E. coli + Vancomycin or Linezolid for MRSA coverage.
- For suspected or confirmed Acinetobacter baumannii, empiric options include: Meropenem, Colistin or Tigecycline.
Central Nervous System Infections
Common Pathogens for Bacterial Meningitis are:
- Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae,
- Listeria monocytogenes (in immunocompromised or elderly individuals)
Empiric Therapy:
- Ceftriaxone + Vancomycin ± Ampicillin (Ampicillin is added due to Listeria coverage in elderly or immunocompromised individuals)
- Dexamethasone IV: add to empiric antibiotic regimen, it reduces inflammation and edema, reduces risk of hearing loss and mortality.
Bacterial meningitis prevention
For close contacts of patients with bacterial meningitis and for family members, partners, roommates, or individuals who had >8 hours of contact to infected person you need to prescribe antibiotics for chemoprophylaxis of bacterial meningitis. It can be done with either Rifampin, Ciprofloxacin or Ceftriaxone, shown on a picture.
Otitis media
Otitis media may be caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis,
drug of choice is Amoxicillin-clavulanate.
Infective Endocarditis
Native Valve Endocarditis:
- Common pathogens: S. aureus, Enterococcus spp., Viridans streptococci (S. mitis, S. sanguinis, S. oralis, S. salivarius),
- HACEK group consists of Gram-negative bacterias (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) that are part of the normal oral flora. They can cause a small proportion of infective endocarditis, particularly in individuals with pre-existing heart conditions.
Empiric treatment for native valve endocarditis is: Vancomycin + Ceftriaxone combination. Vancomycin covers gram positive bacterias and Ceftriaxone adds synergy and gram negative coverage and it is a drug of choice for HACEK organisms. For patients with suspected oral or GI source Ampicillin-Sulbactam may be used instead of Ceftriaxone in combination with Vancomycin.
Prosthetic Valve Endocarditis:
- Empiric treatment: Vancomycin + Gentamicin + Cefepime or Carbapenem
Vancomycin covers MRSA and streptococci. Gentamicin provides synergistic activity against enterococci and staphylococci. Cefepime offers additional anti-pseudomonal coverage and is often included in empiric regimens. Carbapenems (e.g. Meropenem) may be used instead of Cefepime if multidrug-resistant (MDR) Gram-negative organisms are suspected.
Neutropenic Fever
Neutropenic fever (aka Febrile neutropenia) is a life threatening medical condition characterized by the onset of fever >38 degrees in individuals with neutropenia. Neutropenia is classified on a picture.
When absolute neutrophil count (ANC) is <500 there is increased risk for bacterial infections. In neutropenic fever we need empiric antibiotic that covers: Pseudomonas, E. coli, Klebsiella, Staphylococcus aureus
- First-line treatment is Cefepime, a 4th generation cephalosporin.
- Alternatives: Piperacillin-tazobactam or Meropenem, add Vancomycin if MRSA suspected.
Sepsis
- Cefepime or Piperacillin-tazobactam ± Vancomycin (for MRSA) ± Metronidazole (for Anaerobes)
- Consider Carbapenems for ESBL-producing organisms
- Early fluid resuscitation and ICU support are essential.
Mycobacterial Infections
Tuberculosis is caused by Mycobacterium tuberculosis complex
- Traditional regimen: Isoniazid, Rifampin, Ethambutol, Pyrazinamide (≥6 months)
- Shortened regimen: Isoniazid, Rifapentine, Moxifloxacin, Pyrazinamide (~4 months)
Do Not use shortened regimen if patient has cardiovascular disease, chronic kidney disease, liver failure or if a patient is pregnant. In pregnancy and lactation WHO recommends traditional 6 month regimen with Isoniazid, Rifampin, Ethambutol and Pyrazinamide.
Note: Isoniazid can cause deficiency of Pyridoxine (vitamin B6) and when prescribing Isoniazid it is absolutely important to supplement a patient with Pyridoxine in order to avoid development of peripheral neuropathy, seizures, sideroblastic anemia and pellagra. These side effects are due to Pyridoxine deficiency and are associated during Isoniazid treatment.
Leprosy is caused by Mycobacterium Leprae complex (Mycobacterium leprae and Mycobacterium lepromatosis) it has 2 forms and treatment duration is dependent on a form.
- Tuberculoid form is treated by: Dapsone + Rifampin combination and treatment duration is 12 months.
- Lepromatous form is treated by: Dapsone + Rifampin + Clofazimine combination for 24 months.
Empiric antibiotic therapy requires a careful balance between timely action and informed decision-making. Recognizing likely pathogens based on clinical presentation and patient risk factors is essential for effective initial treatment. Clinical approach to antibacterial management involves taking bacterial cultures before antibiotic exposure, then starting and continuing empiric treatment until the culture results are available. As culture results become available, therapy should always be adjusted accordingly to optimize outcomes and prevent resistance.
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Author: Mamuka Asatiani