Table 1 Selected studies reporting treatment effects of antibiotics in human TBI

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