Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function

Abstract

Fosfomycin has been used to treat carbapenem‐resistant Acinetobacter baumannii (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different dosage regimens of CRAB treatment in critically ill patients based on their renal function. Monte Carlo simulations were conducted to assess the probability of achieving time above the minimum inhibitory concentration (T > MIC) of 80% and 100% and to determine the cumulative fraction response (CFR) against institutional MICs. Our results demonstrated that administering fosfomycin 20–24 g/day to individuals with normal renal function (CrCl ≥60 mL/min) achieved the target at a MIC of ≤64 and ≤32 μg/mL during the first 24 h of treatment and at steady state, respectively. Notably, those with renal impairment achieved higher MIC values at a steady state despite dosage reduction. None of the regimens reached the target CFR. Our study suggested that administering fosfomycin at least 20 g/day to those with normal renal function provides sufficient exposure throughout the treatment course when the MIC value is ≤32 μg/mL. Less aggressive dosing regimens are advisable for patients with renal impairment. Additional clinical studies are necessary to verify our suggestions.

Study Highlights.

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Fosfomycin has been used to treat Carbapenem‐resistant Acinetobacter baumannii (CRAB) infections. The optimal dosing regimens for critically ill patients, especially those with renal impairments, have not been thoroughly studied.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study utilized Monte Carlo simulations to assess the probability of achieving the pharmacokinetic/pharmacodynamic (PK/PD) targets of several fosfomycin dosage regimens for the treatment of CRAB infection in critically ill patients with varying degrees of renal function.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study provides optimized fosfomycin dosing regimens for treating CRAB infections in critically ill patients with different degrees of renal function. The findings emphasize the potential benefits of employing less aggressive dosing strategies in individuals with renal impairment to minimize the risk of adverse events while still achieving the target drug exposure.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study demonstrates the utility of Monte Carlo simulations in guiding optimal dosage regimens to attain PK/PD targets for treating drug‐resistant pathogens, including CRAB. The findings encourage further investigation of effective regimens through clinical study.

INTRODUCTION

Acinetobacter baumannii is widely acknowledged as a source of hospital‐acquired infections in severely ill individuals, particularly those with ventilator‐associated pneumonia and catheter‐related bloodstream infections. ¹ The organism commonly acquires various mechanisms of resistance, including an increased expression of efflux pumps, decreased permeability, and synthesis of carbapenemase enzymes. These mechanisms result in resistance to carbapenems and other antibiotics that are generally reserved for the treatment of severe infections. The increasing global prevalence of carbapenem‐resistant A. baumannii (CRAB) presents a significant public health concern. Patients who are infected with CRAB have a higher risk, twice as much, of developing sepsis, septic shock, and mortality compared with those who have the susceptible strain. ² Promptly initiating effective antibiotics is essential for mitigating unfavorable outcomes associated with the infection. Selecting the effective antibiotic, however, remains challenging due to its resistance to multiple classes of antibiotics. Repurposing old antibiotics by utilizing them in combination may be a valuable strategy for CRAB treatment.

Fosfomycin, a cell wall synthesis inhibitor, is one of the reserved antibiotics used in combination for the treatment of CRAB. This agent penetrates effectively into serum, urine, cerebrospinal fluid, skin, and lung tissue ³ and exhibits in vitro synergistic or additive effects against CRAB when combined with other antibiotics, including colistin, imipenem, and sulbactam. ⁴ , ⁵ , ⁶ Consequently, various fosfomycin combination regimens, such as fosfomycin–colistin, fosfomycin–carbapenems, and fosfomycin–tigecycline, have been used in clinical practice to treat CRAB ⁷ , ⁸ due to their promising in vitro activities. Previous clinical studies highlighted that treatment with a fosfomycin combination regimen associated with more favorable microbiological outcomes ⁸ and improved survival rates. ⁷ , ⁹ Nonetheless, the optimal dosage of fosfomycin showed inconsistency and was not thoroughly evaluated in the clinical studies.

Fosfomycin exhibits limited binding to plasma proteins and is extensively distributed throughout several tissues. ³ It is mainly excreted unchanged in the urine by glomerular filtration. Previous population pharmacokinetic study of fosfomycin in critically ill patients demonstrated a substantially lower clearance (CL) and larger volume of distribution (Vd) compared with healthy subjects. ¹⁰ Additionally, the pharmacokinetics of fosfomycin exhibit high interindividual variability, especially in critically ill patients. ¹⁰ Therefore, pharmacokinetic/pharmacodynamic (PK/PD) studies have played a crucial role in optimizing dosage for drug‐resistance pathogens, achieving a balance between effectiveness and safety. ¹¹ , ¹² Although previous PK/PD studies have identified the optimal dosage of fosfomycin for treating CRAB in critically ill patients, ¹³ , ¹⁴ these studies are unable to provide specific dosage recommendations for individuals with impaired renal function. Renal impairment, especially in critically ill patients, has been found to have a considerable impact on fosfomycin concentration and the ability to reach the desired pharmacodynamic target. ¹⁰ Thus, this study aimed to evaluate the optimal dosage regimens of intravenous fosfomycin for CRAB treatment in critically ill patients according to renal function.

METHODS

Microbiology

The CRAB clinical isolates were obtained from patients admitted to Maharaj Nakorn Chiang Mai Hospital, Thailand, between January 1, 2019 and January 31, 2023. Fosfomycin minimal inhibitory concentration (MIC) was determined using the Epsilometer test (Etest) method. Briefly, the Etest strip (BioMérieux, USA) reinforced with glucose‐6‐phosphate (Liofilchem, Italy) was applied to the surface of the Mueller–Hinton agar plate (Biomedia, Thailand). The MIC value was read from the scale where the eclipse edge intersects the strip.

Pharmacokinetic/pharmacodynamic (PK/PD) target indices

The PK/PD study of fosfomycin in a neutropenic murine thigh infection model demonstrated that the time above the minimal inhibitory concentration (T > MIC) value of 76.4% corresponded to a 1 − log₁₀ CFU kill of Pseudomonas aeruginosa. ¹⁵ Due to the paucity of in vitro data against A. baumannii, the T > MIC values of 80% and 100% were utilized as our PK/PD targets.

Pharmacokinetic simulation

The Monte Carlo simulations were conducted using NONMEM® (version 7.3, Icon Development Solution, Ellicott City, MD, USA). The model and PK parameters were obtained from the previously published population pharmacokinetics of fosfomycin in critically ill patients. ¹⁰ In brief, the pharmacokinetics of fosfomycin were described by a two‐compartment model with zero‐order input and first‐order elimination. The between‐subject variability was included in the clearance (CL) and volume of distribution of the central compartment (V_C). Simulated concentrations were obtained by taking into account both inter‐subject variability and residual unexplained variability in order to account for parameter uncertainty. The values of pharmacokinetic parameters used in the simulations are presented in Table S1. Fosfomycin concentrations were simulated from various intravenous dosing regimens based on the manufacturer's recommendation (Kent Pharma UK Limited) ¹⁶ and our suggestions. The evaluated fosfomycin dosage ranged from 4 to 24 g/day, given every 6 to 24 h by 1‐, 4‐h, or continuous infusion, as shown in Table 1. Each dosing regimen was simulated for critically ill patients with low (40–60 kg) and high (61–80 kg) body weights, and various degrees of renal function estimated by Cockcroft‐Gault equation (15–29, 30–59, 60–89, and 90–120 mL/min). The assignment of body weight and renal function values to each individual in each group was conducted randomly. A total of 10,000 virtual patients were simulated for each body weight and renal function category for every dosing regimen.

TABLE 1.

Simulated intravenous fosfomycin dosage regimens.

Total daily dose (g)	Dosing regimens	Administration (h)
24	8 g q8hr a	1
		4
	6 g q6hr	1
		4
	8 g LD then 16 g CI b
20	4 g LD then 16 g CI b
18	6 g q8hr a	1
		4
16	4 g q6hr	1
		4
	8 g q12hr a	4
12	4 g q8hr a	4
	6 g q12hr a	1
8	4 g q12hr a	1
	2 g q6hr	1
6	2 g q8hr	1
4	2 g q12hr a	1

Abbreviations: CI, continuous infusion; g, grams; hr, hours; LD, loading dose; q, every.

^a Dosage regimens modified from the manufacturer's recommendation.

^b The loading dose was administered over 30 min, followed immediately by the maintenance doses.

The probability of target attainment (PTA) was calculated as the percentage of simulated patients that had a probability of achieving the defined PK/PD target for a given dosing regimen across various MICs. The cumulative fraction response (CFR) was calculated from PTAs based on the MIC distribution of fosfomycin against CRAB from Maharaj Nakorn Chiang Mai Hospital, Thailand. Dosing regimens that attained at least 90% of PTA and CFR were considered optimal for the documented and empirical treatment of CRAB infection, respectively.

All procedures adhered to the ethical standards of the Helsinki Declaration. Ethics approval for the study was granted through an exemption review by the Research Ethics Committee of the Faculty of Medicine, Chiang Mai University (Approval No: NONE‐2565‐08880), including a waiver of informed consent.

RESULTS

MIC distribution

A total of 57 non‐duplicated CRAB isolates were obtained from various clinical specimens, including sputum, blood, urine, and pus, over the study period. The majority of clinical specimens (84.46%) were sputum. The MIC ranged from 128 to >1024 μg/mL. The MIC50 and MIC90 values were 256 and >1024 μg/mL, respectively (Figure 1).

FIGURE 1.

MIC distribution of fosfomycin against 57 CRAB clinical isolates.

PK/PD simulations

The probability of achieving 100% T > MIC within the first 24 h of treatment and 80% T > MIC at a steady state for each fosfomycin dosing regimen in critically ill patients with varying degrees of renal function is presented in Figures 2 and 3. The probability of achieving T > MIC was similar between low and high body weights (data were not shown).

FIGURE 2.

Probability of achieving 100% T > MIC at the first 24 h for each fosfomycin dosage regimen in critically ill patients with various degrees of renal function. (a) CrCl 90–120 mL/min, (b) CrCl 60–89 mL/min, (c) CrCl 30–59 mL/min, (d) CrCl 15–29 mL/min. The bar plot represents the relative frequency of the institutional MIC distribution across MICs.

FIGURE 3.

Probability of achieving 80% T > MIC at the steady state for each fosfomycin dosage regimen in critically ill patients with various degrees of renal function. (a) CrCl 90–120 mL/min, (b) CrCl 60–89 mL/min, (c) CrCl 30–59 mL/min, (d) CrCl 15–29 mL/min. The bar plot represents the relative frequency of the institutional MIC distribution across MICs.

Within the first 24 h of treatment, all fosfomycin dosing regimens achieved a PTA above 90% at an MIC of ≤16 μg/mL, regardless of renal function. The maximum MIC for achieving a PTA above 90% was 64 μg/mL. A daily dosing regimen of 24 g/day, with an 8 g loading dose followed by a 16 g continuous infusion, achieved a PTA above 90% at an MIC of 64 μg/mL in patients with a CrCl of 90–120 mL/min. None of the fosfomycin regimens reached over 90% PTA for the MIC50 and MIC90 of 256 and >1024 μg/mL, respectively.

At a steady state, the majority of fosfomycin dosing regimens achieved a PTA above 90% at an MIC of ≤32 μg/mL. A PTA above 90% was attained for most of the regimens at a maximum MIC of 64 μg/mL, solely among patients with a CrCl <60 mL/min. Administering a daily dose of 20–24 g, either with an 8 g loading dose or a 4 g loading dose followed by a 16 g continuous infusion, achieved a PTA above 90% PTA at a MIC of 32 μg/mL in patients with a CrCl of ≥60 mL/min. None of the fosfomycin regimens attained over 90% PTA for the MIC50 and MIC90 of 256 and >1024 μg/mL, respectively.

All fosfomycin dosing regimens demonstrated less than 90% CFR against the MIC distribution of the CRAB clinical isolates (Tables S2 and S3).

DISCUSSION

Although fosfomycin has been proposed as a potential treatment for CRAB, the most effective dosing regimens for this medication have not been thoroughly studied. Furthermore, there is a lack of knowledge addressing the adjustment of dosage based on renal function. This study is the first assessment of several fosfomycin dosing schedules in critically ill individuals with various degrees of renal function.

The MIC range of fosfomycin against CRAB observed in this study was 128 to >1024 μg/mL, consistent with findings reported in the related studies (128–2048 μg/mL). ¹³ , ¹⁴ The considerably high MIC50 and MIC90 values observed also align with prior studies, corresponding to 256 and >1024 μg/mL, respectively. ¹³ , ¹⁴ However, a study conducted at a tertiary care hospital in Thailand reported lower MIC50 (128 μg/mL) and MIC90 (256 μg/mL) values, encompassing a broader range of 32 to >2048 μg/mL. ¹⁷ The discrepancy in MIC results could be attributed to the differences in antibiotics consumption rates and infection control strategies among institutions. These consistently high MIC values strongly indicate the potential benefit of PK/PD‐based dosing optimization for enhancing fosfomycin effectiveness.

Fosfomycin demonstrated a concentration‐dependent killing effect against Enterobacterales, including Escherichia coli and Klebsiella pneumoniae. Conversely, it exhibited a time‐dependent killing effect in Staphylococcus aureus and Pseudomonas aeruginosa, with effectiveness primarily associated with T > MIC. ¹⁵ , ¹⁸ , ¹⁹ , ²⁰ Given the limited in vitro data on fosfomycin's efficacy against A. baumannii, this study chose T > MIC values of 80% and 100% as PK/PD targets based on the time‐dependent killing effect observed in P. aeruginosa. ¹⁵ These targets were chosen considering the shared microbiological characteristic of non‐lactose fermentation observed in both A. baumannii and P. aeruginosa. Maintaining a 100% T > MIC for time‐dependent antimicrobials could also enhance clinical and microbiological responses among patients with severe infections. ²¹ These targets have been used in previously published PK/PD studies of fosfomycin against A. baumannii. ¹³ , ¹⁴

Physiological changes caused by critical illness have an impact on several pharmacokinetic parameters of antimicrobial agents, especially those that are water‐soluble. These changes in pharmacokinetic (PK) can have a substantial effect on the concentration of drugs and the attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets. ²² A prior population pharmacokinetic study of fosfomycin in critically ill patients revealed decreased clearance and increased volume of distribution in comparison to noncritically ill individuals. ¹⁰ The study revealed considerable variability in fosfomycin clearance during the treatment course, ranging from 2.06 to 5.57 L/h on days 1–7 after drug administration. Additionally, the significant impact of creatinine clearance and body weight was suggested for fosfomycin clearance and volume of distribution. Given that this is the only population pharmacokinetic (PK) model available for critically ill patients, we employed it in our simulations to accurately represent the pharmacokinetics of fosfomycin in this particular patient population. The model integrated all relevant pharmacokinetic parameters and important variables to simulate drug concentrations throughout the treatment regimen in critically ill patients with different body weights and renal functions. Assessing the efficacy of each regimen involved calculating %PTA and %CFR during the initial 24 h (first day) and at the steady state (fifth day), thereby ensuring the attainment of PK/PD targets throughout the treatment period.

In our simulations, we observed consistent achievement of PK/PD targets among critically ill patients with low (40–60 kg) and high (61–80 kg) body weights, albeit with a slight variation in attainment percentage. This finding is consistent with a previous PK study, which recommended similar dosage regimens due to the negligible impact of body weight on PK/PD target achievement. ²³

Early initiation of appropriate antimicrobial treatment has been documented to improve clinical outcomes in critically ill patients with severe infection. ²⁴ , ²⁵ However, administering conventional dosages during the early stage of treatment often leads to inadequate serum concentrations, resulting in unfavorable clinical outcomes. ²⁶ , ²⁷ Although the significance of early appropriate therapy is acknowledged, none of the previous studies have examined the optimal dosage of fosfomycin for the initial stage of CRAB treatment, particularly within the first 24 h. Our simulation results showed that all fosfomycin dosing regimens had a probability of over 90% to achieve 100% T > MIC within the first 24 h, regardless of renal function, when the MIC value was ≤16 μg/mL. Notably, the regimens with a loading dose followed by continuous infusion attained the target at a higher MIC of ≤64 μg/mL, even in those with normal renal function (CrCl ≥60 mL/min). This finding aligns with a previous PK study, which observed significantly improved MIC achievement during the first 24 h of treatment with a continuous infusion strategy. ²⁸ However, thrombophlebitis associated with the continuous infusion may pose a burden for certain individuals, particularly those with problematic veins. ²⁸ Our simulations showed that administering 24 g/day by intermittent (1‐h) or prolonged (4‐h) infusion resulted in a MIC achievement of ≤32 μg/mL. This suggested that these dosage regimens could potentially be used as alternate treatment options for this population. Remarkably, we noted that when the same daily dosage was given, higher dosages provided at each interval resulted in a higher achievement of MICs in patients with impaired renal function. However, similar phenomena were not found in individuals with normal renal function. This may be attributed to the fact that patients with impaired renal function display greater drug accumulation, resulting in a prolonged duration of fosfomycin concentration above the MIC.

The results from our study showed that at the steady state, the highest manufacturer's recommended daily dose of 24 g/day ¹⁶ achieved approximately 90%PTA at an MIC value of 32 μg/mL in critically ill patients with normal renal function. This finding is consistent with the previous PK study suggesting that fosfomycin administered at a dose of 24 g/day achieved a desired T > MIC target at the highest MIC of 32 μg/mL. ²⁹ Despite this, additional research has demonstrated that the PK/PD target can be met at this dosage, even with a higher MIC value of 128 μg/mL. ¹³ , ¹⁴ Variations in the utilized PK parameters and the defined PK/PD target could explain this discrepancy. Although these studies utilized the same population PK model, the clearance values applied in the simulations varied as a result of the fluctuation in clearance values throughout the course of treatment. In our study, the clearance value on the fifth day was utilized for simulations to ensure steady‐state conditions across various levels of renal function. Furthermore, those studies did not examine the substantial influence of renal function on fosfomycin concentrations. ¹³ , ¹⁴ Additionally, the use of different PK/PD targets in each study—both AUC_0‐24/MIC and T > MIC—may partially account for this discrepancy. However, the relevant PK/PD target of fosfomycin against A. baumannii remains limited and is still under debate. Several published PK/PD studies ¹³ , ¹⁴ consequently adopted the target from P. aeruginosa. Our study utilized the T > MIC, considering its association with a 1 − log₁₀ killing effect on P. aeruginosa. ¹⁵ Moreover, optimizing T > MIC offers an additional advantage in preventing the emergence of resistant subpopulations. ¹⁵ , ³⁰

For patients with normal renal function, we observed that prolonged and continuous infusion improved the achievement rates at the steady state, which aligns with previous PK studies. ¹⁴ , ³¹ This is not surprising as fosfomycin exhibits time‐dependent characteristics. Unfortunately, this improvement was not observed among those with impaired renal function (CrCl <60 mL/min). Furthermore, prolonged and continuous infusion is correlated with decreased occurrences of electrolyte imbalance, including hypokalemia and hypernatremia. ³² Thus, these approaches can increase the probability of attaining desired PK/PD outcomes while minimizing the risk of adverse events.

The influence of renal function on fosfomycin clearance was significant. ¹⁰ Patients with normal renal function required a maximum daily dose of 24 g to achieve a PTA greater than 90% at an MIC of ≤32 μg/mL. Patients with impaired renal function required lower dosages to achieve the same target. Patients with a CrCl between 30 and 59 mL/min and 15 and 29 mL/min achieved a PTA of over 90% at an MIC value of ≤64 μg/mL with a total daily dose of at least 16 g (4 g every 6 h) and 6 g (2 g every 8 h), respectively. Although it was recommended that patients with impaired renal function require a lower dose of fosfomycin, the target was found to be achieved at a higher MIC when the lower dose was administered. For instance, in patients with normal renal function, the recommended dose of 20 g/day resulted in achieving a PTA greater than 90% at a MIC of ≤32 μg/mL, while patients with CrCl between 30 and 59 mL/min would achieve a PTA greater than 90% at a MIC of ≤64 μg/mL with the recommended dose of 16 g/day. Interestingly, this finding was not observed in the previous PK study, ²³ which could contribute to the difference in the desired PK/PD target as we discussed earlier. Nevertheless, it is important to acknowledge that although these regimens show promising levels of %PTA, they have not undergone assessment in clinical studies, and certain high‐dosage regimens were above the recommended doses provided by the manufacturer. ¹⁶ Therefore, clinicians must carefully assess the potential advantages and disadvantages of administering such high doses. The dosage reduction in those with impaired renal function is suggested to mitigate the potential adverse effects of electrolyte imbalance.

The results from our study revealed that none of the fosfomycin regimens attained a CFR above 90% against the institution's MIC distribution, which is consistent with results from previous studies. ¹³ , ¹⁴ Based on a previous PK study of fosfomycin, a mean maximum concentration of 357 ± 28 μg/mL was observed, ³³ which is much lower than the MIC90 of 1024 μg/mL in our setting. The markedly low CFR suggests that fosfomycin monotherapy might not be an appropriate option for empirical treatment of CRAB infections in our institution and other settings with similarly high resistance rates. However, in vitro studies have indicated that combining fosfomycin with other antibiotics reduced its MIC against CRAB. ⁴ , ¹³ , ¹⁴ , ³⁴ Likewise, several clinical studies have reported improved clinical or microbiological outcomes with fosfomycin combination therapy. ⁷ , ⁸ , ⁹ Fosfomycin combination therapy may be considered an option for treating CRAB infections, particularly in settings with available MIC data to guide treatment decisions. Nevertheless, our simulation indicated that its effectiveness might be limited to infections with MIC below 32 and 64 μg/mL in patients with normal and impaired renal function, respectively. Thus, it is recommended to explore other combined drugs for treating CRAB infections with higher MICs.

Providing optimal antibiotic dosing requires a thorough understanding of PK/PD principles. Our study demonstrates the value of computerized simulations as a translational tool to effectively bridge the gap between theoretical PK/PD principles and real‐world dosing practices. This approach could enhance treatment precision and effectiveness for critically ill patients, potentially improving patient outcomes. However, our study has some limitations. First, the population pharmacokinetic model used in our simulations was developed with a small sample size, which may affect its ability to identify significant covariates. However, based on the model evaluation findings, it appears that the model adequately described the pharmacokinetics and their variability of fosfomycin in critically ill patients. Despite this limitation, the simulation results obtained from our study provide useful information for guiding the optimal dosing regimen of fosfomycin in critically ill patients. Second, the susceptibility was conducted using the Etest method, which exhibited a categorical agreement of 64.3% with the standard agar dilution method in A. baumannii. ³⁵ Although this discrepancy might affect the interpretation of fosfomycin MIC results, the MIC distribution, MIC50, and MIC90 remained consistent with findings from previous studies employing the agar dilution method. ¹³ , ¹⁴ Additionally, the MIC values were obtained from a teaching hospital with a high resistance rate. Consequently, dosing regimens tailored specifically to CFR might not directly apply to other settings with substantially lower resistance rates. Finally, the suggestion of certain dosing regimens in our study was based solely on PK/PD target achievement results with limited or no supporting clinical data. Therefore, it is crucial to carefully consider the risks and advantages associated with employing these regimens, while acknowledging the need for confirmation through clinical investigations. Furthermore, the findings of our study specifically explored the use of fosfomycin as a monotherapy. Nevertheless, the results could provide suggestions for optimal fosfomycin dosing when the MIC of fosfomycin in combination with the specific agent is known.

CONCLUSIONS

Our study suggests that administering fosfomycin at a daily dose of at least 20 g/day proves successful in providing sufficient exposure to critically ill patients with normal renal function, when the MIC value is ≤32 μg/mL. Furthermore, among this cohort of patients, the administration of prolonged fosfomycin infusion resulted in a higher percentage of %PTA. With regard to those experiencing a decline in renal function, it is advisable to use less aggressive dosing regimens in order to maintain a balance between the potential risks and benefits. Combining fosfomycin with other active agents is suggested to enhance the likelihood of achieving the PK/PD target and potentially improve clinical outcomes. Additional clinical investigations are necessary for verifying our suggestions.

AUTHOR CONTRIBUTIONS

N.T., P.L., and B.P. wrote the manuscript. N.T., P.W., and B.P. designed the research. N.T., A.C., S.C., S.L.P., and B.P. performed the research. N.T., P.L., and B.P. analyzed the data.

FUNDING INFORMATION

This work (Grant No. RGNS 65‐066) was supported by the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation (OPS MHESI), Thailand Science Research and Innovation (TSRI), and Chiang Mai University. The funding sources have no role in the study design, data collection, analysis and interpretation, or report writing.

CONFLICT OF INTEREST STATEMENT

The authors declared no competing interests in this work.

Supporting information

Tables S1‐S3

Tidwong N, Chanruang A, Chupradit S, et al. Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function. Clin Transl Sci. 2024;17:e70038. doi: 10.1111/cts.70038

DATA AVAILABILITY STATEMENT

The supporting data are available upon reasonable request from the corresponding author.