====== Antimicrobial therapy ======

**[[Antimicrobial]] [[Therapy]]** refers to the use of agents, such as [[antibiotic]]s, [[antifungal]]s, [[antiviral]]s, and antiparasitics, to treat infections caused by [[microorganism]]s, including [[bacteria]], [[fungi]], [[virus]]es, and parasites. The primary goals of antimicrobial therapy are to eradicate the causative pathogen, minimize harm to the host, and prevent the development of antimicrobial resistance. Here's a general overview:

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### **1. Types of Antimicrobials**
- **Antibiotics**: Target bacteria (e.g., penicillin, ciprofloxacin).
- **Antifungals**: Target fungi (e.g., fluconazole, amphotericin B).
- **Antivirals**: Target viruses (e.g., oseltamivir, remdesivir).
- **Antiparasitics**: Target parasites (e.g., metronidazole, ivermectin).

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### **2. Principles of Antimicrobial Therapy**
- **Empirical Therapy**: Initiated before the exact pathogen is identified, often based on clinical judgment and epidemiological data.
- **Targeted Therapy**: Based on the identification of the pathogen and its susceptibility profile.
- **Prophylactic Therapy**: Used to prevent infections, particularly in high-risk populations or surgical settings.
- **Combination Therapy**: Employing multiple agents to broaden the spectrum, achieve synergistic effects, or prevent resistance.

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### **3. Pharmacokinetics and Pharmacodynamics**
- **Absorption, Distribution, Metabolism, and Excretion**: These factors determine how the antimicrobial reaches and maintains therapeutic levels at the site of infection.
- **Concentration-Dependent Killing**: Efficacy increases with drug concentration (e.g., aminoglycosides).
- **Time-Dependent Killing**: Efficacy relies on maintaining levels above the minimum inhibitory concentration (MIC) for an extended period (e.g., beta-lactams).

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### **4. Resistance and Stewardship**
- **Antimicrobial Resistance (AMR)**: A critical challenge where pathogens no longer respond to treatments due to misuse or overuse of antimicrobials.
- **Antimicrobial Stewardship Programs (ASP)**:
  - Ensure the appropriate selection, dosage, and duration of therapy.
  - Monitor resistance trends.
  - Educate healthcare providers on responsible use.

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### **5. Key Considerations in Antimicrobial Therapy**
- **Host Factors**: Age, immune status, renal/hepatic function, allergies.
- **Pathogen Factors**: Susceptibility patterns, virulence.
- **Drug Factors**: Side effects, drug interactions, cost, and formulation.

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### **6. Examples of Guidelines**
- **Community-Acquired Pneumonia (CAP)**: Empiric therapy often includes beta-lactams combined with macrolides or respiratory fluoroquinolones.
- **Sepsis**: Broad-spectrum antibiotics initiated promptly, later narrowed based on cultures.
- **Tuberculosis**: Long-course therapy with multiple agents like isoniazid and rifampin to prevent resistance.
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[[Postoperative intracranial neurosurgical infection]]s (PINI) complicate < 5% neurosurgeries. Scarce attention was dedicated to the extension and characteristics of its antimicrobial management considering their high morbidity, not negligible mortality, delayed hospital stay and increased healthcare costs.

They analyzed [[retrospective]]ly (2014-2023) 162 PINI from eight Spanish third-level [[academic hospital]]s.

[[Elective]] clean craniotomies after tumor or vascular causes were the leading procedures. [[Epidural abscess]] (24.7%), [[scalp infection]]s (19.8%), [[postsurgical meningitis]] (16.7%) and [[cranioplasty infection]]s (16.7%) were the most frequent PINI. [[Gram negative bacteria]] (38.6%) and Staphylococcus spp (28.6%) were the predominant isolates. Overall 85.2% patients underwent [[pus]] drainage, mostly by [[craniotomy]] (40.3%). Interestingly 34% were already receiving [[antibiotic]]s for extracranial infections before developing PINI while 16.8% did not receive pre-operative antibiotic prophylaxis. In total 77.2% patients started a combined intravenous (IV) antimicrobial therapy, of which 85.2% switched after 5 days to a second-line IV antibiotic regimen, in 41.3% cases combined, after pus culture results, for a median of 21 days. Overall 61.1% patients continued on oral antimicrobials after hospital discharge, 30.3% as a combined regimen, for a median of 42 days. Complete cure was obtained in 81.5% cases, while 11.1% relapsed, 7.4% failed to cure and 6.8% died after PINI complications. In the [[multivariate]] analysis oral antimicrobial therapy after hospital discharge (p = 0.001) was significantly associated with PINI cure with no effect on survival.

They conclude that an extended 6 weeks sequential IV and oral antimicrobial therapy in addition to neurosurgical correction increases PINI cure rate with no effect on survival
((Asensi V, Vázquez-Fernández C, Suárez-Díaz S, Asensi-Díaz E, Carrasco-Antón N, García-Reyne A, Panero I, Muñoz MV, Guerra JM, Arístegui J, Sepúlveda MA, García-Calvo X, Dueñas C, Biosca M, Chiminazzo V, Collazos J. Extended sequential intravenous and oral antimicrobial therapy improves cure rate in postoperative intracranial neurosurgical infections: a Spanish multicenter retrospective study. BMC Infect Dis. 2024 Nov 26;24(1):1345. doi: 10.1186/s12879-024-10204-7. PMID: 39587499.))