Skip to main content

Tazobactam/ceftolozane and tobramycin combination therapy in extensively drug-resistant Pseudomonas aeruginosa infections in severe burn injury: a case report

Abstract

Background

Combination therapy with tazobactam/ceftolozane (TAZ/CTLZ) and high-dose aminoglycosides has been reported to be efficacious in extensively drug-resistant (XDR)-Pseudomonas aeruginosa infection. However, there are no reports of efficacy in XDR-P. aeruginosa infection for combination therapy with low-dose aminoglycosides and TAZ/CTLZ. Herein, we describe a rare case of severe burn injury patients with persistent bacteremia due to XDR-P. aeruginosa, which was successfully treated with TAZ/CTLZ and low-dose tobramycin (TOB).

Case presentation

A 31-year-old man was admitted to the intensive care unit with severe burn injury involving 52% of the total body surface area and a prognostic burn index of 79.5. The patient had recurrent bacterial infections since admission, and blood cultures collected on the 37th day of admission revealed the presence of P. aeruginosa strains that were resistant to all β-lactams and amikacin (AMK). The results of the antimicrobial synergistic study showed no synergistic effect of low-dose meropenem (MEPM) and AMK combination therapy. The patient had acute renal failure, and it was difficult to increase the dose of MEPM and AMK, respectively. Thus, we initiated TAZ/CTLZ 1.5 g/8 h instead of the AMK and MEPM combination therapy on the 43rd day of hospitalization. Low-dose TAZ/CTLZ was continued because of prolonged renal dysfunction and resulted in a transient clinical improvement. However, the dosage of TAZ/CTLZ could be increased as the renal function improved, but despite an increased TAZ/CTLZ dose, bacteremia persisted, and the blood cultures remained positive. Thus, TOB was added to TAZ/CTLZ at low doses for synergistic effect against Gram-negative bacteria. Blood cultures collected after initiation of combination therapy with TAZ/CTLZ and low-dose TOB were negative on two consecutive follow-up evaluations. Thereafter, although the patient had several episodes of fever and increased inflammatory response, blood cultures consistently tested negative, and all of the wounds healed. On the 93rd day, due to the good healing progress, the patient was transferred to another hospital.

Conclusions

TAZ/CTLZ and low-dose TOB combination therapy showed the potential for synergistic effects. Our present report suggests a novel synergistic treatment strategy for rare cases that are refractory to the treatment of infections, such as XDR-P. aeruginosa infection.

Introduction

Burn patients in the out of acute-phase of their injury experience a range of clinical problems [1], with one key factor being the higher prevalence of drug-resistant bacteria [2], which further complicates their treatment. In particular, Pseudomonas aeruginosa causes systemic infections through wound infections and is associated with an increased mortality in burn care units [3].

Tazobactam/ceftolozane (TAZ/CTLZ) is a novel antibacterial drug combination, comprising a cephalosporin (ceftolozane) and a beta (β)-lactamase inhibitor (tazobactam) [4]. This drug is effective against P. aeruginosa [5]; however, TAZ/CTLZ is not effective against carbapenemase-producing strains [6] but is effective against AmpC- and extended-spectrum β-lactamase-producing strains. TAZ/CTLZ has demonstrated high activity against P. aeruginosa, in vitro [7] and is expected to be effective against 90% of primary β-lactam-resistant strains [8]. Therefore, TAZ/CTLZ might be effective against multidrug-resistant (MDR) and extensively drug-resistant (XDR)-P. aeruginosa isolates. However, MDR- and XDR-P. aeruginosa strains have decreased susceptibility to β-lactams, quinolones, and aminoglycosides, and monotherapy with any antibiotic has limited efficacy. Notably, combination therapy with β-lactams and aminoglycosides or quinolones may be considered empirical for the treatment of severe P. aeruginosa infections [9]. High-dose aminoglycoside antibiotics have been shown to be effective against XDR-P. aeruginosa in combination therapy with TAZ/CTLZ [10, 11]; however, to our knowledge, there are no reports of efficacy for combination therapy with low-dose aminoglycosides used synergistically with TAZ/CTLZ.

Herein, we describe the first case of severe burn injury with persistent bacteremia due to XDR-P. aeruginosa, which was successfully treated with a combination of TAZ/CTLZ and low-dose tobramycin (TOB).

Case presentation

A 31-year-old man was admitted to the intensive care unit with severe burn injury involving 52% of the total body surface area and a prognostic burn index of 79.5. The clinical data recorded at the time of hospitalization are presented in Table S1. After hospitalization, an escharotomy was immediately performed, and fluid resuscitation and mechanical ventilatory management were initiated. Devices, such as central venous catheter, arterial line, and flexible double lumen catheter, were inserted. The patient developed acute kidney injury (AKI) and received continuous renal replacement therapy (CRRT) immediately after hospitalization.

The first surgical debridement was performed on the 3rd day of hospitalization. On the fourth day of hospitalization, the patient developed fever and decreased blood pressure. Meropenem (MEPM) and linezolid (LZD) were initiated as treatment for septic shock. Blood and wound culture results revealed the presence of Klebsiella species, Serratia marcescens, Enterobacter cloacae complex, and several other indigenous skin bacteria. Based on the susceptibilities of the bacterial species that were identified, MEPM and LZD were replaced with sulbactam/ampicillin (SBT/ABPC) and ceftazidime (CAZ) to target bacteria, excluding indigenous skin bacteria. Subsequently, the surgical debridement was performed on the 5th and 10th days of hospitalization. Since the clinical course was favorable and blood samples collected and cultured at the follow-up evaluation were negative for the target bacteria, both SBT/ABPC and CAZ administration were discontinued after the 5-day regimen.

The second skin graft surgery was performed on the 29th day after admission; carbapenem-resistant P. aeruginosa was detected for the first time in the burn wounds and in sputum cultures collected before grafting (Table 1). Amikacin (AMK) monotherapy was selected as a perioperative therapeutic strategy for burn wounds (Fig. 1). However, because the patient was receiving CRRT support for AKI due to burns, the blood levels of AMK did not reach the target peak concentration required for therapeutic effect. Furthermore, trough concentrations remained high; therefore, the dose was reduced and continued. AMK blood concentration results are shown in Table S4. Thereafter, a chest X-ray showed partial loss of permeability in the right lung field, and an increased inflammatory response was confirmed, possibly due to postoperative ventilator management, suggesting the possibility of ventilator-associated pneumonia. As AMK diffuses poorly in the lung tissue, MEPM was included as a treatment for pneumonia caused by P. aeruginosa, and the ventilator was weaned off. However, the blood sample collected at the follow-up evaluation revealed β-lactams and AMK-resistant P. aeruginosa. The drug susceptibility results of P. aeruginosa detected in blood cultures (blood culture samples at days 37, 41, 50, and 56) are shown in Table 1. The antimicrobial synergistic study of P. aeruginosa was conducted using the Eiken breakpoint checkerboard plate (BC plate®) (Fig. 2). The results were analyzed using the interpretive criteria defined by the Clinical and Laboratory Standards Institute. Notably, the low-dose MEPM and AMK combination therapy did not exhibit a synergistic effect. Due to the patient’s AKI complications, it was difficult to increase the MEPM and AMK doses.

Table 1 Antibiotic sensitivity test results of the isolated Pseudomonas aeruginosa
Fig. 1
figure 1

Clinical course of this case. Abbreviations: AMK, amikacin; BT, body temperature; CRP, C-reactive protein; TAZ/CTLZ, tazobactam/ceftolozane; MEPM, meropenem; TOB, tobramycin

Fig. 2
figure 2

Antimicrobial Synergy Study – Checkerboard Testing Abbreviations: AMK, amikacin; AZT, aztreonam; CAZ, ceftazidime; CPFX, ciprofloxacin; CL, colistin; MEPM, meropenem; PIPC, piperacillin; RFP, rifampicin. Representation of a checkerboard assay where the synergistic effect of two antibiotics is depicted. In this illustration, “no growth” is represented in white, and “growth” is represented in black

Therefore, we initiated TAZ/CTLZ 1.5 g/8 h instead of the AMK and MEPM combination therapy on the 43rd day of hospitalization (Fig. 1). Although the antimicrobial susceptibility test of TAZ/CTLZ could not be performed on the day of hospitalization, the results of the genetic analysis confirmed that P. aeruginosa that was isolated was a non-carbapenemase-producing strain. The patient could be weaned off from CRRT on the 40th day of hospitalization, but low-dose TAZ/CTLZ was continued because of prolonged renal dysfunction, which resulted in a transient clinical improvement. The third skin graft surgery was performed on the 46th day of hospitalization. However, fever and an increased inflammatory response were observed, and XDR-P. aeruginosa was detected on the blood culture as in previous blood cultures. The treatment could have failed due to underdosing with TAZ/CTLZ or bacterial resistance to TAZ/CTLZ at that time. Therefore, the TAZ/CTLZ dose was increased to 3 g/8 h in accordance with the renal function.

The fourth skin graft surgery was performed on the 57th day of hospitalization. However, despite an increased TAZ/CTLZ dose, bacteremia persisted, and the blood cultures remained positive. Because of the limited therapeutic effect of TAZ/CTLZ monotherapy, the TOB susceptible to this isolate (180 mg/24 h) was initiated. TOB was added on TAZ/CTLZ at low doses for synergistic effect against Gram-negative bacteria. The therapeutic drug monitoring results of TOB are shown in Table S2. Blood cultures collected after initiation of combination therapy with TAZ/CTLZ and TOB were negative on two consecutive follow-up evaluations. Since the blood cultures were negative, the patient’s persistent bacteremia was considered to be under control. Moreover, since P. aeruginosa may become resistant to TAZ/CTLZ with long-term use, a higher dose of TOB was considered in order to switch to standard therapy for Gram-negative bacteria. In addition, since the clinical course was favorable, TOB was increased as standard monotherapy against Gram-negative bacteria, and the peak concentration measured on the 69th day of hospitalization reached the therapeutic response range. Combination therapy with TAZ/CTLZ and TOB was continued for 10 days, and then treatment with TOB as a monotherapy was continued for the remainder of the treatment period, which was set at 14 days after negative blood cultures. Thereafter, although the patient had several episodes of fever and increased inflammatory response, blood cultures consistently tested negative, and all of the wounds healed. On the 93rd day of hospitalization, due to the good healing progress, the patient was transferred to another hospital.

Although susceptibility testing of TAZ/CTLZ was not possible, we performed retrospective antimicrobial susceptibility testing of TAZ/CTLZ on P. aeruginosa isolated from blood cultures as an additional analysis (Table S3). The results from samples collected before TAZ/CTLZ administration showed that one of the isolates was resistant, while another showed intermediate susceptibility.

Discussion

This report describes a significant clinical case where TAZ/CTLZ and low-dose TOB combination therapy was successfully used to treat XDR-P. aeruginosa infection in a patient with severe burns. To our knowledge, this treatment approach has not been previously reported.

In patients with severe burns, infection is the most common complication that is associated with an increased mortality risk [3]. The burn wound is initially colonized by a higher proportion of Gram-positive bacteria with continued antimicrobial therapy, these bacteria are often replaced by Gram-negative ones [12]. A 50% increase in mortality has been reported in patients with burns having Gram-negative bacteremia compared with those without bacteremia [13]. Moreover, due to the increasing antibiotic resistance, the treatment of infections has become difficult and has contributed to the increased mortality rate. Furthermore, MDR-P. aeruginosa causes 4–60% of nosocomial infections, which leads to high mortality and morbidity in patients with burns [14, 15]. Therefore, controlling P. aeruginosa and preventing the development of antibiotic-resistant strains is crucial for infection control in burn wards and successful treatment of burns. In this case, XDR-P. aeruginosa was detected within 1 month after the first positive blood culture, and bacteremia caused by this isolate persisted; thus, controlling XDR-P. aeruginosa was necessary for the successful treatment of this patient.

Combination therapy with more than two antibiotics with anti-P. aeruginosa activity is recommended for the treatment of severe P. aeruginosa infections to decrease the risk of treatment failure. Among the effective regimens, the β-lactam and aminoglycoside combination is frequently used, and this combination is effective against MDR-P. aeruginosa infections [16, 17]. In this case, the MEPM and AMK combination therapy used to treat XDR-P. aeruginosa infection did not result in any clinical improvement. A possible cause of treatment failure was that this patient had AKI and was receiving low doses of MEPM and AMK. In support of this, a synergistic study of antibacterial activity against resistant P. aeruginosa showed that the combination of MEPM and AMK at low doses did not show a synergistic effect (Fig. 2).

A recent study reported that TAZ/CTLZ therapy is more effective than colistin, polymyxin, or aminoglycoside-based regimens, in severe P. aeruginosa infections. The CEFTABUSE registry results showed that the 14-day clinical cure rates of TAZ/CTLZ administration were more effective than those of aminoglycosides and polymyxin, although the difference was not statistically significant [18]. A retrospective cohort study showed that TAZ/CTLZ administration was independently associated with clinical cure compared with colistin- or aminoglycoside-based regimens [19]. These two studies indicated that the incidence of AKI was significantly lower with the TAZ/CTLZ treatment group, indicating that TAZ/CTLZ can be an effective option for patients with renal dysfunction or those with a high risk of nephrotoxicity. However, in this case, treatment with TAZ/CTLZ monotherapy failed to suppress the persistent bacteremia caused by resistant P. aeruginosa. This could be due to the fact that retrospective P. aeruginosa drug susceptibility testing had revealed a TAZ/CTLZ-resistant strain.

In our case, persistent bacteremia caused by resistant P. aeruginosa was controlled after initiation of combination therapy with TAZ/CTLZ and low-dose TOB. We believe that the fact that blood cultures became negative on two consecutive follow-up evaluations after the start of combination therapy with TAZ/CTLZ and TOB proves the effectiveness of the combination therapy. The success of this combination therapy supported two previous reports [10, 11]. An in vitro study has assessed the efficacy of a combination therapy of TAZ/CTLZ and an aminoglycoside [10], demonstrating that the TAZ/CTLZ and AMK combination therapy has synergistic effects and may therefore be useful in treating MDR-P. aeruginosa infections. In another study conducted on febrile neutropenic patients with concurrent TAZ/CTLZ -resistant P. aeruginosa infection, the combination of TAZ/CTLZ and TOB synergistically decreased the respective minimal inhibitory concentration values [11]. Thus, in our case, the addition of TOB improved the anti-microbial effects and possibly enhanced the efficacy of TAZ/CTLZ. One difference between these two previous reports and the present case is the dosage of TOB. In these two previous studies, the dosing settings were 25 mg/kg/q24h for AMK and 7 mg/kg/q24h for TOB, which were capable of reaching the target peak concentrations required for therapeutic effects. In our case, TOB was initiated at a dose of 3 mg/kg, which is much lower than the dose required to achieve the target peak concentration to produce a therapeutic effect (5–7 mg/kg/q24h). Furthermore, renal function at the time of TOB initiation in this patient was eGFRcreat > 130 mL/min/1.73 m2, a condition suspicious for augmented renal clearance (ARC). Previous reports suggest that the recommended dose of TOB in patients with ARC is 7 mg/kg/day to achieve pharmacodynamic goals [20]. It has also been reported that split doses or higher doses may be required to reach target peak concentrations in severe burn patients with increased volume of distribution and increased clearance [21, 22]. Generally, when TOB is administered at a low dose for its synergistic effects against Gram-negative bacteria, its peak concentration is not routinely measured. However, actual measured TOB trough concentrations (Table S2) and patient factors also suggest that the effective peak concentration has not been reached. Despite a low dose of TOB for persistent bacteremia, the success in achieving negative blood culture results suggests an enhanced synergistic efficacy of the TAZ/CTLZ and TOB combination therapy.

We did not select quinolones as an antibiotic treatment option for XDR-P. aeruginosa. Although quinolones constitute effective therapeutic options for P. aeruginosa infections, a meta-analysis indicated that the use of quinolones increased the risk of MDR- or XDR-P. aeruginosa compared with that of resistant or susceptible P. aeruginosa [23]. Therefore, the use of quinolones was avoided here to prevent P. aeruginosa from acquiring multidrug or extensive drug resistance.

In our case, TAZ/CTLZ susceptibility testing of P. aeruginosa-resistant strains was performed retrospectively, which has rarely been reported of P. aeruginosa strains that acquired resistance prior to TAZ/CTLZ exposure in Japan. The stability of TAZ/CTLZ against the main resistance mechanisms of P. aeruginosa, such as OprD deficiency, increased AmpC production, and drug excretion proteins [6, 24], underscores that TAZ/CTLZ resistance can result from the intense use of other β-lactam antibiotics that can induce or inhibit AmpC production, independently of TAZ/CTLZ use [25]. Therefore, it is possible that the use of multiple β-lactam antibiotics during the 1-month burn treatment period contributed to the development of TAZ/CTLZ resistance. However, the mechanisms driving TAZ/CTLZ resistance need to be further explored. Notably, the combination of TAZ/CTLZ and low-dose aminoglycoside antibiotics may be an effective antimicrobial treatment option, even in P. aeruginosa strains that exhibit TAZ/CTLZ resistance.

A limitation of this study is that no antimicrobial synergism study of TAZ/CTLZ and TOB was conducted; therefore, TOB monotherapy may have been more effective than TAZ/CTLZ and TOB synergistic therapy. Therefore, future antimicrobial synergistic studies of TAZ/CTLZ and low-dose aminoglycosides in vitro should be conducted to clearly distinguish between additive and synergistic effects. However, we consider it a clinically serious finding that in the present case, treatment with TAZ/CTLZ and low-dose TOB resulted in negative blood cultures for XDR-P. aeruginosa bacteremia resistant to TAZ/CTLZ.

In conclusion, this case highlights the efficacy of a combination therapy with TAZ/CTLZ and low-dose TOB in managing persistent XDR-P. aeruginosa bacteremia in patients with severe burns. Furthermore, the combination of TAZ/CTLZ with low-dose TOB is a promising antimicrobial option for TAZ/CTLZ-resistant P. aeruginosa infections. Further research is warranted to validate the findings of this study and explore the potential benefits and limitations of this regimen.

Availability of data and materials

Not applicable.

Abbreviations

TAZ/CTLZ:

Tazobactam/ceftolozane

MDR:

Multidrug-resistant

XDR:

Extensively drug-resistant

TOB:

Tobramycin

AKI:

Acute kidney injury

CRRT:

Continuous renal replacement therapy

MEPM:

Meropenem

LZD:

Linezolid

SBT/ABPC:

Sulbactam/ampicillin

CAZ:

Ceftazidime

AMK:

Amikacin

ARC:

Augmented renal clearance

References

  1. Norbury W, Herndon DN, Tanksley J, Jeschke MG, Finnerty CC. Infection in burns Surg Infect (Larchmt). 2016;17:250–5.

    Article  PubMed  Google Scholar 

  2. Li L, Dai JX, Xu L, et al. Antimicrobial resistance and pathogen distribution in hospitalized burn patients: A multicenter study in Southeast China. Medicine (Baltimore). 2018;97:e11977.

    Article  PubMed  Google Scholar 

  3. Fournier A, Voirol P, Krähenbühl M, et al. Antibiotic consumption to detect epidemics of Pseudomonas aeruginosa in a burn centre: A paradigm shift in the epidemiological surveillance of Pseudomonas aeruginosa nosocomial infections. Burns. 2016;42:564–70.

    Article  PubMed  Google Scholar 

  4. Sader HS, Rhomberg PR, Farrell DJ, Jones RN. Antimicrobial activity of CXA-101, a novel cephalosporin tested in combination with tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis strains having various resistance phenotypes. Antimicrob Agents Chemother. 2011;55:2390–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Craig WA, Andes DR. In vivo activities of ceftolozane, a new cephalosporin, with and without tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, including strains with extended-spectrum β-lactamases, in the thighs of neutropenic mice. Antimicrob Agents Chemother. 2013;57:1577–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhanel GG, Chung P, Adam H, et al. Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs. 2014;74:31–51.

    Article  CAS  PubMed  Google Scholar 

  7. Sid Ahmed MA, Abdel Hadi H, Hassan AAI, et al. Evaluation of in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against MDR Pseudomonas aeruginosa isolates from Qatar. J Antimicrob Chemother. 2019;74:3497–504.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Goodlet KJ, Nicolau DP, Nailor MD. In Vitro comparison of ceftolozane-tazobactam to traditional beta-lactams and ceftolozane-tazobactam as an alternative to combination antimicrobial therapy for Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017;61:e01350-e1417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bassetti M, Vena A, Croxatto A, Righi E, Guery B. How to manage Pseudomonas aeruginosa infections. Drugs Context. 2018;7:212527.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Galani I, Papoutsaki V, Karantani I, et al. In vitro activity of ceftolozane/tazobactam alone and in combination with amikacin against MDR/XDR Pseudomonas aeruginosa isolates from Greece. J Antimicrob Chemother. 2020;75:2164–72.

    CAS  PubMed  Google Scholar 

  11. So W, Shurko J, Galega R, Quilitz R, Greene JN, Lee GC. Mechanisms of high-level ceftolozane/tazobactam resistance in Pseudomonas aeruginosa from a severely neutropenic patient and treatment success from synergy with tobramycin. J Antimicrob Chemother. 2019;74:269–71.

    CAS  PubMed  Google Scholar 

  12. Wanis M, Walker SAN, Daneman N, et al. Impact of hospital length of stay on the distribution of Gram negative bacteria and likelihood of isolating a resistant organism in a Canadian burn center. Burns. 2016;42:104–11.

    Article  PubMed  Google Scholar 

  13. Sharma BR. Infection in patients with severe burns: causes and prevention thereof. Infect Dis Clin North Am. 2007;21(745–59):ix.

    PubMed  Google Scholar 

  14. Morales E, Cots F, Sala M, et al. Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. BMC Health Serv Res. 2012;12:122.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Biswal I, Arora BS, Kasana D, Neetushree. Incidence of multidrug resistant Pseudomonas aeruginosa isolated from burn patients and environment of teaching institution. J Clin Diagn Res 2014; 8: DC26–9.

  16. Dundar D, Otkun M. In-vitro efficacy of synergistic antibiotic combinations in multidrug resistant Pseudomonas aeruginosa strains. Yonsei Med J. 2010;51:111–6.

    Article  CAS  PubMed  Google Scholar 

  17. Tait JR, Bilal H, Rogers KE, et al. Effect of different piperacillin-tazobactam dosage regimens on synergy of the combination with tobramycin against Pseudomonas aeruginosa for the pharmacokinetics of critically ill patients in a dynamic infection model. Antibiotics (Basel). 2022;11:101.

    Article  CAS  PubMed  Google Scholar 

  18. Pogue JM, Kaye KS, Veve MP, et al. Ceftolozane/tazobactam vs polymyxin or aminoglycoside-based regimens for the treatment of drug-resistant Pseudomonas aeruginosa. Clin Infect Dis. 2020;71:304–10.

    Article  CAS  PubMed  Google Scholar 

  19. Vena A, Giacobbe DR, Mussini C, et al. Clinical efficacy of ceftolozane-tazobactam versus other active agents for the treatment of bacteremia and nosocomial pneumonia due to drug-resistant Pseudomonas aeruginosa. Clin Infect Dis. 2020;71:1799–801.

    Article  CAS  PubMed  Google Scholar 

  20. Hobbs ALV, Shea KM, Roberts KM, Daley MJ. Implications of augmented renal clearance on drug dosing in critically Ill patients: A focus on antibiotics. Pharmacotherapy. 2015;35:1063–75.

    Article  CAS  PubMed  Google Scholar 

  21. Bracco D, Landry C, Dubois MJ, Eggimann P. Pharmacokinetic variability of extended interval tobramycin in burn patients. Burns. 2008;34:791–6.

    Article  PubMed  Google Scholar 

  22. Conil JM, Georges B, Breden A, et al. Increased amikacin dosage requirements in burn patients receiving a once-daily regimen. Int J Antimicrob Agents. 2006;28:226–30.

    Article  CAS  PubMed  Google Scholar 

  23. Raman G, Avendano EE, Chan J, Merchant S, Puzniak L. Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2018;7:79.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Livermore DM, Mushtaq S, Ge Y, Warner M. Activity of cephalosporin CXA-101 (FR264205) against Pseudomonas aeruginosa and Burkholderia cepacia group strains and isolates. Int J Antimicrob Agents. 2009;34:402–6.

    Article  CAS  PubMed  Google Scholar 

  25. Torrens G, Hernández SB, Ayala JA, et al. Regulation of AmpC-driven β-lactam resistance in Pseudomonas aeruginosa: different pathways, different signaling. mSystems 2019; 4: e00524–19.

Download references

Acknowledgements

We thank the Departments of Emergency Medicine and Infection Control and Laboratory Medicine, as well as all the colleagues at our institution, for their contribution to the medical care of the patient at Sapporo Medical University Hospital.

Funding

This study was not funded.

Author information

Authors and Affiliations

Authors

Contributions

YI wrote the first draft of this manuscript. RK, HI, and YF were involved in patient's pharmaceutical care and revised the manuscript. TI, HI, SU, and SF advised on the interpretation of the therapeutic course in this case and revised the manuscript. ST, EN, and MF supervised the writing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masahide Fukudo.

Ethics declarations

Ethics approval and consent to participate

For this case report, the need for ethics approval and consent to participate was waived by the institutional review board.

Consent for publication

Written consent for publication was obtained from the patient as a comprehensive consent form upon admission to the intensive care unit.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1

. Laboratory data. Table S2. Blood concentration level of tobramycin. Table S3. Antimicrobial susceptibility testing of tazobactam/ceftolozane against Pseudomonas aeruginosa. Table S4. Blood concentration level of amikacin.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ibe, Y., Kakizaki, R., Inamura, H. et al. Tazobactam/ceftolozane and tobramycin combination therapy in extensively drug-resistant Pseudomonas aeruginosa infections in severe burn injury: a case report. J Pharm Health Care Sci 9, 25 (2023). https://doi.org/10.1186/s40780-023-00294-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40780-023-00294-x

Keywords