What is the clinical available evidence for the usage of minocycline in patients with Burkholderia cepacia complex infections?

Comment by InpharmD Researcher

There is very limited evidence supporting the use of minocycline for treating Burkholderia cepacia complex (Bcc) infections, with available data primarily consisting of in vitro studies and case reports. In vitro research has demonstrated adequate bactericidal activity of minocycline against Bcc, with one study suggesting enhanced activity when combined with meropenem. Minocycline is not considered a first-line agent for Bcc infections, and reviews typically recommend its use in combination with other active antibiotics. Overall, there is currently a scarcity of data to support the use of minocycline for the treatment of Bcc infections.

Background

A 2015 review discusses treatment strategies for management of nonfermenter infections, including Burkholderia cepacia complex (Bcc). While discussions were limited, it was noted that minocycline and tigecycline had a susceptibility rate between 5.5 and 44.4%. Therefore, a variable activity is observed. However, tigecycline has poor activity due to drug efflux, so recommendations are limited to minocycline as a second-line or combination agent. [1]

A 2021 study analyzed the susceptibility of minocycline against clinically significant gram-negative pathogens, including Burkholderia spp., in samples collected from the United States and Europe. Minocycline susceptibility was shown to be good overall, though susceptibility towards Burkholderia ssp. Was on the lower end (86.8%) compared to other pathogens. MIC50 was 2 mg/L and MIC 90 was 8 mg/L. Note that the majority of Burkholderia ssp. samples were the Bcc which reported a susceptibility rate of 86.3% in isolation to minocycline. [2]

A 2019 in vitro study evaluated the activity of minocycline against the Bcc, based on the SENTRY Antimicrobial Surveillance Program. Minocycline was found to be effective against the majority of Bcc as 88.1% of the tested bacterial strains were inhibited by minocycline at a concentration of 4 mcg/mL or lower. The MIC50 was 2 mcg/mL, and the MIC90 was 8 mcg/mL. Therefore, minocycline was considered an effective treatment option, although resistance has been observed. [3]

A 2000 publication explored multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. Given the significant resistance of B. cepacia strains to standard antibacterial treatments, the research aimed to evaluate in vitro the effectiveness of various antibiotic combinations. The investigation included 119 multi-drug-resistant isolates and assessed the bactericidal activity of 10 to 15 antimicrobial agents in 225 single, double, and triple antibiotic combinations. Findings highlighted that while 50% of isolates were resistant to all single antibiotics tested, each displayed susceptibility to at least one triple-drug combination. A double antibiotic combination with meropenem and minocycline was bactericidal against 76% of isolates. Triple combinations containing tobramycin and meropenem proved most effective, with bactericidal activity against 81% to 93% of the isolates. [4]

The 2022 article presented a retrospective chart review that involved 44 patients who developed Bcc infections at non-respiratory sites. These patients were admitted between June 2005 and February 2020. Data collection focused on the epidemiological background, associated risk factors, antibiotic regimens employed, and susceptibilities of the Bcc isolates. The primary sites of infection included bacteremia (38.6%), followed by skin and soft tissue infections (36.4%) and vertebral osteomyelitis (18.2%). The majority of the Bcc isolates demonstrated susceptibility to ceftazidime and carbapenems, with trimethoprim-sulfamethoxazole (TMP-SMX) also showing effectiveness. Directed antibiotic therapy based on susceptibility results led to favorable clinical outcomes, highlighting the effectiveness of tailored treatment strategies. One patient in this review received minocycline, but the details of their infection type and disposition were not provided. [5]

References: [1] Abbott IJ, Peleg AY. Stenotrophomonas, Achromobacter, and nonmelioid Burkholderia species: antimicrobial resistance and therapeutic strategies. Semin Respir Crit Care Med. 2015;36(1):99-110. doi:10.1055/s-0034-1396929
[2] Shortridge D, Arends SJR, Streit JM, Castanheira M. Minocycline Activity against Unusual Clinically Significant Gram-Negative Pathogens. Antimicrob Agents Chemother. 2021;65(11):e0126421. doi:10.1128/AAC.01264-21
[3] Flamm RK, Shortridge D, Castanheira M, Sader HS, Pfaller MA. In Vitro Activity of Minocycline against U.S. Isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus Species Complex, Stenotrophomonas maltophilia, and Burkholderia cepacia Complex: Results from the SENTRY Antimicrobial Surveillance Program, 2014 to 2018. Antimicrob Agents Chemother. 2019;63(11):e01154-19. Published 2019 Oct 22. doi:10.1128/AAC.01154-19
[4] Aaron SD, Ferris W, Henry DA, Speert DP, Macdonald NE. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1206-1212. doi:10.1164/ajrccm.161.4.9907147
[5] Kwayess R, Al Hariri HE, Hindy JR, Youssef N, Haddad SF, Kanj SS. Burkholderia cepacia Infections at Sites Other than the Respiratory Tract: A Large Case Series from a Tertiary Referral Hospital in Lebanon. J Epidemiol Glob Health. 2022;12(3):274-280. doi:10.1007/s44197-022-00048-2
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the clinical available evidence for the usage of minocycline in patients with Burkholderia cepacia complex infections?

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Table 1 for your response.


 

Management of Cepacia Syndrome With a Combination of Intravenous and Inhaled Antimicrobials in a Non-Cystic Fibrosis Pediatric Patient

Design

Case report

Case presentation

A 17-year-old male with chronic granulomatous disease (CGD) presented with right upper-lobe pneumonia. He had a history of recurrent Burkholderia cepacia complex (Bcc) pneumonia previously treated with IV ceftazidime monotherapy. Prior to hospitalization, he was on prophylactic sulfamethoxazole-trimethoprim 800-160 mg oral tablet once daily and itraconazole 100-mg capsule once daily. Upon admission, he was empirically started on ceftazidime 2000 mg every 8 hours and IV vancomycin 1000 mg every 8 hours. After becoming hypoxic and requiring mechanical ventilation, a bronchoalveolar lavage (BAL) on day 2 grew 200 colonies of Bcc. The Infectious Diseases service recommended switching ceftazidime to meropenem 1000 mg every 8 hours due to worsening respiratory status.

On day 5, Bcc sensitivities returned, showing sensitivity to ceftazidime, minocycline, and sulfamethoxazole-trimethoprim, but intermediate sensitivity to meropenem. Antibiotic therapy was immediately switched back to ceftazidime 2000 mg every 8 hours, with continued IV vancomycin. Due to continued decline and suspected cepacia syndrome, the regimen was augmented with minocycline 200-mg capsule enterally twice daily, sulfamethoxazole-trimethoprim (6.4 mg/kg trimethoprim) IV every 8 hours, and tobramycin inhaled 300 mg twice daily for synergistic effect. Upon decannulation from ECMO on day 16, tobramycin inhaled 300 mg twice daily was reinitiated. After extubation on day 19, vancomycin was discontinued, and sulfamethoxazole-trimethoprim was transitioned to oral liquid. On day 28, he was discharged to complete an 8-week course of ceftazidime 2000 mg every 8 hours, minocycline 200-mg capsule twice daily, and sulfamethoxazole-trimethoprim (6.4 mg/kg trimethoprim) oral every 8 hours, alongside a steroid taper.

Study Author Conclusions

The combination of nebulized tobramycin, sulfamethoxazole-trimethoprim, ceftazidime, and enteral minocycline together with systemic corticosteroids led to the successful treatment of cepacia syndrome in the setting of necrotizing pneumonia due to B cepacia. Multimechanistic drug therapy may improve clinical outcomes in patients with cepacia syndrome who continue to decline on traditional IV therapy.
References:
[1] Branstetter JW, Yarbrough A, Poole C. Management of Cepacia Syndrome With a Combination of Intravenous and Inhaled Antimicrobials in a Non-Cystic Fibrosis Pediatric Patient. J Pediatr Pharmacol Ther. 2020;25(8):730-734. doi:10.5863/1551-6776-25.8.730