| Reference | Subjects and survival/follow up | Treatment groups, dosage and route | Treatment effects |
---|---|---|---|---|
Minocycline (MINO) | Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration [57] | Cross-sectional study of patients with ≥ 6 mths after moderate to severe TBI without surgery, age range 20–65 years, ~ 80% male, follow up at 12 wk and 6 mths | 1. Healthy controls (n = 64) 2. TBI, no MINO (n = 5) 3. TBI + MINO (n = 9) oral (100 mg), twice daily for 12 wk, all patients underwent arterial plasma sampling for NFL to evaluate neurodegeneration,11C-PBR28 PET to determine microglial activation, MRI to determine structural data | 1. Reduced chronic microglial activation 2. Increased plasma levels of NFL |
Effects of minocycline on neurological outcomes in patients with acute traumatic brain injury: a pilot study [58] | Prospective randomized study of moderate to severe TBI patients undergoing surgery within 12 h after admission, age range 42.5 ± 15.8 years with 88.2% male, follow up at 6 mths | 1. TBI + placebo (n = 20) 2. TBI + MINO (n = 14) oral (100 mg), oral twice daily, first dose within 24 h after admission then continued 2 times/day for 7 d | 1. Reduced serum levels of NSE at 5d after admission 2. Improvement of GCS values from 1 d to 5 d after admission 3. No difference of 6-mths survival | |
Doxycycline (DOX) | The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial [59] | Randomized-controlled trial of moderate (GCS: 9–12) and severe TBI (GCS: 3–8) patients admitted < 24 h, age range 18–70 years with 50% male, follow up until 28 d after discharge | 1. TBI + placebo (n = 20) 2. TBI + DOX (n = 20), oral (100 mg), twice daily for 7d | 1. Reduced serum levels of NSE at 3 d and 7 d after admission 2. Increased GCS value at 7 d and at discharge 3. No difference in length of stay, number of deaths and mean survival days |
Vancomycin and Meropenem | Efficacy and safety of intrathecal meropenem and vancomycin in the treatment of postoperative intracranial infection in patients with severe traumatic brain injury [60] | Retrospective analysis of patients with intracranial infection after severe TBI and surgical intervention (craniotomy), age range 30 ± 9 years, 53.5% male, all patients survived until the end of the study (6 mths) | 1. Control group (n = 43), vancomycin (1 g) and meropenem (2 g), i.v. administration for 2 wk every 12 h, and meropenem every 8 h 2. Experimental group (n = 43), vancomycin (20 mg) and meropenem 20 mg, intrathecal administration for two weeks, once daily and meropenem twice daily | Intrathecal administration of antibiotics resulted in 1. Improved response rate (reduced intracranial infection) 2. Faster cure time in experimental group 3. Reduced treatment costs 4. Lower incidence of adverse effects |
combined antibiotics | Effects of antibiotic prophylaxis on ventilator-associated pneumonia in severe traumatic brain injury. A post hoc analysis of two trials [54] | Retrospective analysis using two databases collected from 25 ICUs, age range 23–52 years with 85% male, follow up until 28 d after discharge | 1. Control group, no antibiotic prophylaxis (n = 149) 2. Antibiotic prophylaxis (n = 146), 93% (n = 136) i.v. within 2 d after TBI, 72% of the patients received penicillins (mostly amoxicillin-clavulanate), 23% cephalosporins (mostly 1st or 2nd generation), 4% aminoglycosides, 1% 3rd generation cephalosporins and 0.3% metronidazole | 1. Antibiotic prophylaxis reduced the occurrence and early incidence of ventilator-associated pneumonia 2. Mortality was not affected |
Early antibiotic administration is independently associated with improved survival in traumatic brain Injury [53] | Retrospective study on TBI patients admitted to the ICU, age range 59.7 ± 23 years with 65% male, most patients presented with blunt head trauma, recruitment of patients who survived longer than 48 h after admission | 1. EARLY group: Patients with i.v. administration within 48 h after admission including cefazolin, gentamicin or vancomycin followed by additional antibiotics e.g. penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones or tetracyclines (n = 189) 2. Non-EARLY group: Patients who received antibiotics later than 48 h (n = 299, antibiotics not specified) | 1. EARLY patients were younger than non-EARLY (54.2 ± 22.9 vs. 61.5 ± 22.2 years) 2. EARLY group presented with hypotension, lower GCS values, longer hospital and ICU stay and lower risk of mortality 3. Administration of early antibiotics independently correlated with lower mortality | |
Antibiotic prophylaxis in penetrating traumatic brain injury: analysis of a single-center series and systematic review of the literature [61] | 1. Retrospective single-center study, age range 32 ± 13 years, 20 male and 1 female, follow-up until 31 d after admission. 2. Systematic review of 14 studies including patients with penetrating head injury (total n = 327, sex not specified) | Single-center study: 1. Control, no prophylactic antibiotics 2. Cefazolin monotherapy 3. Various regimens of broad-spectrum antibiotics including vancomycin, ceftriaxone, and metronidazole, i.v. first dose within 24 h after admission, the continued up to 30 d Systematic review: 1. No prophylactic antibiotics 2. Single or combination of antibiotic regimen, i.v. at various time points ranging from single injection intra-operatively to repetitive injections for 3–7 d | Single-center study: Reduced numbers of patients with CNS infection after antibiotic prophylaxis (12%) vs. control (75%). Systematic review: (1) Among all patients from 14 studies, 66% received prophylaxis (2) The proportion of CNS infection in patients with and without prophylaxis was 17% and 19%, respectively 3. Short course of prophylactic antibiotics is recommended; i.v. cefazolin or ceftriaxone every 12 h + metronidazole every 6 h if organic debris is present in the wound |