Does ampicillin/sulbactam have any utility in treating brain abscess? (Actinomyces, Fusobacterium, Aggregatibacter sp. polymicrobial abscess). Are adequate concentrations achieved in adults?

Comment by InpharmD Researcher

Limited published data have reported use of ampicillin/sulbactam in treatment of brain abscesses, with case reports describing successful ampicillin/sulbactam treatment of brain abscesses caused by Actinomyces species. Standard dosing has been considered sufficient for central nervous system infections, though individual response may depend on pathogen susceptibility and need for surgical intervention.

Background

Available review articles discuss the potential role of ampicillin sulbactam in treating different infections. A 2002 review article assessed the clinical efficacy of ampicillin/sulbactam in managing severe pediatric infections, highlighting its effectiveness in treating brain abscesses in children. In a study of 21 patients, including those with multiple lesions, treatment at 100/50 mg/kg per day for an average of 48 days was successful, with three deaths unrelated to the infection or therapy (Table 1). Another evaluation of 57 pediatric cases, ranging from 2 months to 16 years old, reported similar outcomes. The findings reinforced ampicillin/sulbactam as a potent empiric therapy for a broad range of pediatric infections, particularly in settings with high beta-lactamase-producing pathogen prevalence. [1], [2]

In general, ampicillin and sulbactam reach high concentration in cerebrospinal fluid (CSF), surpassing the minimum inhibitory concentration (MIC) of key bacterial pathogens. Standard dosing of sulbactam, given as 2 g of ampicillin with 1 g of sulbactam every six hours, has been considered sufficient for crossing the blood-brain barrier though effectiveness may vary based on the extent of meningeal inflammation and the pathogen’s susceptibility. [1], [2]

A 2024 systematic literature review identified 47 eligible reports, encompassing 67 cases of Actinomyces turicensis infections. Most infections involved the anogenital region (31%) or presented as abscess-forming diseases, with concurrent bacteremia observed in 10% of cases. Polymicrobial infection was common, with A. turicensis frequently co-isolated with anaerobes. Empirical treatment strategies varied, though beta-lactams, particularly amoxicillin-clavulanate, were the most frequently used agents; use of ampicillin/sulbactam occurred in 6 cases, though combinations with other antimicrobials and durations of therapy varied. Surgical intervention, including debridement or drainage, was required in 76% of cases. Despite diagnostic challenges, 89% of patients achieved full recovery, while two fatal cases were documented. One case study involving an adult male with a brain abscess caused by A. turicensis is reported in Table 2. [3]

A 1986 pharmacokinetic study characterized the penetration of sulbactam and ampicillin into body fluids and tissues, demonstrating that both compounds extensively diffused into blister fluid, peritoneal fluid, and sputum. While cerebrospinal fluid penetration was generally poor in the absence of inflammation, meningitis facilitated a significant increase in drug concentrations, with sulbactam levels in cerebrospinal fluid reaching up to 32% of serum levels; one patient with a brain abscess had a 9% serum sulbactam level in cerebrospinal fluid. However, discussion on penetration in the presence of specific microorganisms was not discussed. [4]

References: [1] Adnan S, Paterson DL, Lipman J, Roberts JA. Ampicillin/sulbactam: its potential use in treating infections in critically ill patients. Int J Antimicrob Agents. 2013;42(5):384-389. doi:10.1016/j.ijantimicag.2013.07.012
[2] Kanra G. Experience with ampicillin/sulbactam in severe infections. J Int Med Res. 2002;30 Suppl 1:20A-30A. doi:10.1177/14732300020300S104
[3] Imeneo A, Rindi LV, Di Lorenzo A, et al. Brain abscess caused by Actinomyces turicensis in a non-immunocompromised adult patient: a case report and systematic review of the literature. BMC Infect Dis. 2024;24(1):109. Published 2024 Jan 20. doi:10.1186/s12879-024-08995-w
[4] Foulds G. Pharmacokinetics of sulbactam/ampicillin in humans: a review. Clinical Infectious Diseases. 1986;8(Supplement_5):S503-S511.
Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

Does ampicillin/sulbactam have any utility in treating brain abscess? (Actinomyces, Fusobacterium, Aggregatibacter sp. polymicrobial abscess). Are adequate concentrations achieved in adults?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-3 for your response.


Treatment of Intracranial Abscesses: Experience with Sulbactam/Ampicillin
Design

Open prospective study

N= 21

Objective To evaluate the efficacy of sulbactam/ampicillin in patients with intracranial abscesses
Study Groups All patients (N= 21)
Inclusion Criteria Patients admitted with suspected intracranial infection excluding suppurative meningitis, confirmed by CT scan or MRI
Exclusion Criteria Not specified
Methods Patients received intravenous sulbactam/ampicillin (50 and 100 mg/kg/day, respectively) in four divided doses. Surgical intervention was performed in 16 patients, while others were treated with antibiotics alone. Follow-up CT scans were conducted to monitor abscess size reduction
Duration

March 1987 to January 1991

Antibiotic therapy: 48 ± 10 days (range 26-65 days)

Follow-up after completion of therapy: 6 ± 2.4 months

Outcome Measures

Primary: Reduction in size of abscesses within 3 weeks

Secondary: Cure rate, mortality, side effects

Baseline Characteristics Characteristic All patients (N= 21)
Age, years  33 (8-61)
Male 12

Presenting symptoms

Headache

Fever

Lethargy

Nausea and vomiting

Focal neurolog ic deficit

Seizure

Papilledema

Stiffneck

 

18 (86%)

9 (43%)

8 (38%)

7 (33%)

5 (24%)

4 (19%)

4 (19%)

2 (10%)

Results Outcome All patients (N= 21)
Cured 17
Died 3
Reoperated 1

Reduction in abscess size within 3 weeks

21

Brain abscess cultures resulted in the following species: Bacteroides fragilis, Streptococcus pneumoniaes, Staphylococcus aureus, Pepto-streptococcus, Proteus mirabilis, Coagulsse-negative staphylococci 

Adverse Events Side effects of sulbactam/ampicillin were minor and transient, including diarrhea (n= 3) and skin rash (n= 1)
Study Author Conclusions Sulbactam/ampicillin can be used in the treatment of intracranial abscesses, alone or with surgical intervention. It is effective and has minor side effects
Critique The study provides evidence for the efficacy of sulbactam/ampicillin in treating intracranial abscesses, but the small sample size and lack of a control group limit the generalizability of the findings. Further controlled studies are needed to compare its efficacy and safety with other regimens. 
References:
[1] Akova M, Akalìn HE, Korten V, Ozgen T, Erbengi A. Treatment of intracranial abscesses: experience with sulbactam/ampicillin. J Chemother. 1993;5(3):181-185. doi:10.1080/1120009x.1993.11739230

 

Brain abscess Caused by Actinomyces turicensis in a Non-immunocompromised Adult Patient: a Case Report and Systematic Review of the Literature

Design

Case report

Case presentation

A 55-year-old man with a history of alcohol abuse presented with confusion and seizures. Imaging revealed temporal-occipital brain lesions, and intraoperative aspiration identified Actinomyces turicensis and Proteus mirabilis. Initial empiric treatment included ceftriaxone, metronidazole, and linezolid, later optimized to ceftriaxone 2 g q12h monotherapy based on susceptibility results. However, fever and necrotizing lesion of the upper lip and oral cavity followed, thus prompting wound swabbing to determine A. turicensis involvement. The swab returned positive for Herpes simplex virus-1 and carbapenem-resistant Acinetobacter baumannii; thus, ampicillin/sulbactam 3 g q6h was added for coverace of the mucosal lesion isolate and the brain abscess (A. turicensis). Five weeks later, the patient demonstrated significant clinical improvement and radiologic resolution of the abscesses, and was discharged with oral amoxicillin-clavulanate for a total therapy duration of 8 weeks.

Study Author Conclusions

To the best of our knowledge, we hereby present the first case of a brain abscess caused by A. turicensis and P. mirabilis. Brain involvement by A. turicensis is rare and may result from hematogenous spread or by dissemina- tion of a contiguous infection. The infection might be difficult to diagnose and therefore treatment may be delayed

 

References:
[1] Imeneo A, Rindi LV, Di Lorenzo A, et al. Brain abscess caused by Actinomyces turicensis in a non-immunocompromised adult patient: a case report and systematic review of the literature. BMC Infect Dis. 2024;24(1):109. Published 2024 Jan 20. doi:10.1186/s12879-024-08995-w

 

A Rare Case of Brain Abscess Caused by Aggregatibacter aphrophilus and Actinomyces georgiae in an Immunocompetent Child

Design

Case report 

Case presentation

An immunocompetent 10-year-old female experienced a brain abscess caused by Aggregatibacter aphrophilus and Actinomyces. The patient presented with a 10-day history of severe, intractable headache accompanied by visual disturbances, nausea, and vomiting. Notably, she had a history of secundum atrial septal defect and had undergone dental procedures for caries one month prior to admission. Brain MRI resulted in right parietal lobe mass, suggesting brain abscess. Surgical intervention was performed via craniotomy with abscess aspiration, and initial microbial cultures identified A. aphrophilus, a gram-negative coccobacillus commonly associated with invasive infections following dental procedures. Additionally, gram-positive filamentous bacteria were observed, prompting further molecular analysis. Subsequent 16S rRNA sequencing confirmed the presence of A. georgiae, marking the first reported case of central nervous system infection caused by this species in an immunocompetent child. Following surgical drainage, empirical antimicrobial therapy with cefotaxime and metronidazole was initiated but later transitioned at day 17 to ampicillin-sulbactam 3 g every 6 hours based on culture susceptibility results (minimum inhibitory concentration 0.5 mcg/mL). The patient received seven weeks of intravenous treatment followed by one week of oral amoxicillin-clavulanate. Serial imaging demonstrated progressive resolution of the abscess, with MRI at two months confirming complete obliteration of the residual pocket. The patient recovered without neurological sequelae, and subsequent closure of the atrial septal defect was performed without complication.

Study Author Conclusions

In this report, we describe a case of a central nervous system infection caused by Aggregatibacter aphrophilus and Actinomyces pathogens in an immunocompetent child and successful treatment with ampicillin-sulbactam.
References:
[1] Bae S, Lee SJ, Kim YK, et al. A Rare Case of Brain Abscess Caused by Aggregatibacter aphrophilus and Actinomyces georgiae in an Immunocompetent Child. 2023 Dec;30(3):159-164. Pediatr Infect Vaccine. doi:10.14776/piv.2023.30.e16