Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis

doi:10.1128/AAC.01746-20

. 2020 Dec 16;65(1):e01746-20.

doi: 10.1128/AAC.01746-20. Print 2020 Dec 16.

Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis

Itaru Nakamura¹, Tetsuo Yamaguchi², Kotaro Aoki³, Yuri Miura¹, Satoko Sato¹, Hiroaki Fujita¹, Hidehiro Watanabe¹

Affiliations

¹ Department of Infection Prevention and Control, Tokyo Medical University Hospital, Tokyo, Japan.
² Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University, Tokyo, Japan tetsuo.yamaguchi@med.toho-u.ac.jp.
³ Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University, Tokyo, Japan.

PMID: 32958715
PMCID: PMC7927830
DOI: 10.1128/AAC.01746-20

Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis

Itaru Nakamura et al. Antimicrob Agents Chemother. 2020.

. 2020 Dec 16;65(1):e01746-20.

doi: 10.1128/AAC.01746-20. Print 2020 Dec 16.

Authors

Itaru Nakamura¹, Tetsuo Yamaguchi², Kotaro Aoki³, Yuri Miura¹, Satoko Sato¹, Hiroaki Fujita¹, Hidehiro Watanabe¹

Affiliations

¹ Department of Infection Prevention and Control, Tokyo Medical University Hospital, Tokyo, Japan.
² Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University, Tokyo, Japan tetsuo.yamaguchi@med.toho-u.ac.jp.
³ Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University, Tokyo, Japan.

PMID: 32958715
PMCID: PMC7927830
DOI: 10.1128/AAC.01746-20

Abstract

We applied combination antibiotic therapy to treat vertebral osteomyelitis and a psoas abscess caused by glycopeptide-intermediate (MIC, 2 μg/ml) and daptomycin-nonsusceptible (>2 μg/ml) methicillin-resistant Staphylococcus aureus The Etest synergy test showed the largest synergistic effects for imipenem/cilastatin and fosfomycin. Whole-gene sequencing showed amino acid changes in SA0802, SA1193 (mprF), and SA1531 (ald). Four weeks of combination treatment using imipenem/cilastatin (1.5 g per day) and fosfomycin (4.0 g per day) resulted in clinical improvement.

Keywords: Etest synergy test; antibiotic combination; fosfomycin; imipenem; whole genome analysis.

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Comment in

Case Commentary: Imipenem/Cilastatin and Fosfomycin for Refractory Methicillin-Resistant Staphylococcus aureus Infection: a Novel Combination Therapy.
Sakoulas G. Sakoulas G. Antimicrob Agents Chemother. 2020 Dec 16;65(1):e02039-20. doi: 10.1128/AAC.02039-20. Print 2020 Dec 16. Antimicrob Agents Chemother. 2020. PMID: 33020155 Free PMC article.

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Tedeschi S, Giannitsioti E, Mayer C. Tedeschi S, et al. Microorganisms. 2025 Apr 23;13(5):963. doi: 10.3390/microorganisms13050963. Microorganisms. 2025. PMID: 40431135 Free PMC article. Review.
Case Commentary: Imipenem/Cilastatin and Fosfomycin for Refractory Methicillin-Resistant Staphylococcus aureus Infection: a Novel Combination Therapy.
Sakoulas G. Sakoulas G. Antimicrob Agents Chemother. 2020 Dec 16;65(1):e02039-20. doi: 10.1128/AAC.02039-20. Print 2020 Dec 16. Antimicrob Agents Chemother. 2020. PMID: 33020155 Free PMC article.
Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia.
Wenzler E, Adeel A, Wu T, Jurkovic M, Walder J, Ramasra E, Campion M, Cerny J, Theodoropoulos NM. Wenzler E, et al. Infect Dis Rep. 2021 Sep 8;13(3):843-854. doi: 10.3390/idr13030076. Infect Dis Rep. 2021. PMID: 34563001 Free PMC article.
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Pignatti M, Dolci G, Zamagni E, Pascale R, Piccin O, Ammar A, Zeneli F, Miralles MEL, Mancuso K, Cipriani R, Viale P, Pacini D, Martin-Suàrez S. Pignatti M, et al. Microorganisms. 2023 Nov 3;11(11):2699. doi: 10.3390/microorganisms11112699. Microorganisms. 2023. PMID: 38004712 Free PMC article.

References

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1. Tsukimori A, Nakamura I, Okamura S, Sato A, Fukushima S, Mizuno Y, Yamaguchi T, Matsumoto T. 2014. First case report of vancomycin-intermediate sequence type 72 Staphylococcus aureus with nonsusceptibility to daptomycin. BMC Infect Dis 14:459. doi:10.1186/1471-2334-14-459. - DOI - PMC - PubMed
1. Yamaguchi T, Suzuki S, Okamura S, Miura Y, Tsukimori A, Nakamura I, Ito N, Masuya A, Shiina T, Matsumoto T. 2015. Evolution and single-nucleotide polymorphisms in methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to vancomycin and daptomycin, based on determination of the complete genome. Antimicrob Agents Chemother 59:3585–3587. doi:10.1128/AAC.05159-14. - DOI - PMC - PubMed

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[1] Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF, Infectious Diseases Society of America. 2011. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 52:e18–e55. doi:10.1093/cid/ciq146. - DOI - PubMed

[2] Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF, Infectious Diseases Society of America. 2011. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 52:e18–e55. doi:10.1093/cid/ciq146. - DOI - PubMed

[3] Blot SI, Vandewoude KH, Hoste EA, Colardyn FA. 2002. Outcome and attributable mortality in critically ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Arch Intern Med 162:2229–2235. doi:10.1001/archinte.162.19.2229. - DOI - PubMed

[4] Blot SI, Vandewoude KH, Hoste EA, Colardyn FA. 2002. Outcome and attributable mortality in critically ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Arch Intern Med 162:2229–2235. doi:10.1001/archinte.162.19.2229. - DOI - PubMed

[5] Miro JM, Anguera I, Cabell CH, Chen AY, Stafford JA, Corey GR, Olaison L, Eykyn S, Hoen B, Abrutyn E, Raoult D, Bayer A, Fowler VG, International Collaboration on Endocarditis Merged Database Study Group. 2005. Staphylococcus aureus native valve infective endocarditis: report of 566 episodes from the International Collaboration on Endocarditis Merged Database. Clin Infect Dis 41:507–514. doi:10.1086/431979. - DOI - PubMed

[6] Miro JM, Anguera I, Cabell CH, Chen AY, Stafford JA, Corey GR, Olaison L, Eykyn S, Hoen B, Abrutyn E, Raoult D, Bayer A, Fowler VG, International Collaboration on Endocarditis Merged Database Study Group. 2005. Staphylococcus aureus native valve infective endocarditis: report of 566 episodes from the International Collaboration on Endocarditis Merged Database. Clin Infect Dis 41:507–514. doi:10.1086/431979. - DOI - PubMed

[7] Tsukimori A, Nakamura I, Okamura S, Sato A, Fukushima S, Mizuno Y, Yamaguchi T, Matsumoto T. 2014. First case report of vancomycin-intermediate sequence type 72 Staphylococcus aureus with nonsusceptibility to daptomycin. BMC Infect Dis 14:459. doi:10.1186/1471-2334-14-459. - DOI - PMC - PubMed

[8] Tsukimori A, Nakamura I, Okamura S, Sato A, Fukushima S, Mizuno Y, Yamaguchi T, Matsumoto T. 2014. First case report of vancomycin-intermediate sequence type 72 Staphylococcus aureus with nonsusceptibility to daptomycin. BMC Infect Dis 14:459. doi:10.1186/1471-2334-14-459. - DOI - PMC - PubMed

[9] Yamaguchi T, Suzuki S, Okamura S, Miura Y, Tsukimori A, Nakamura I, Ito N, Masuya A, Shiina T, Matsumoto T. 2015. Evolution and single-nucleotide polymorphisms in methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to vancomycin and daptomycin, based on determination of the complete genome. Antimicrob Agents Chemother 59:3585–3587. doi:10.1128/AAC.05159-14. - DOI - PMC - PubMed

[10] Yamaguchi T, Suzuki S, Okamura S, Miura Y, Tsukimori A, Nakamura I, Ito N, Masuya A, Shiina T, Matsumoto T. 2015. Evolution and single-nucleotide polymorphisms in methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to vancomycin and daptomycin, based on determination of the complete genome. Antimicrob Agents Chemother 59:3585–3587. doi:10.1128/AAC.05159-14. - DOI - PMC - PubMed

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Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis

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Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis

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