Is it clinically meaningful to wait for a CK level to return before giving first dose of daptomycin?

Comment by InpharmD Researcher

A literature search did not identify any studies directly evaluating safety or clinical outcomes associated with withholding the first dose of daptomycin until baseline creatinine kinase (CK) levels return to normal. Daptomycin’s prescribing information recommends weekly CK monitoring during therapy and more frequent monitoring with concomitant statin use or renal impairment; however, timing of the baseline CK level relative to administration of the first daptomycin dose is not clearly outlined. Available evidence shows that elevated baseline CK is a risk factor for subsequent development of rhabdomyolysis as opposed to an outright contraindication to daptomycin, especially in patients on concomitant statin therapy, patients with renal impairment, or patients with other rhabdomyolysis risk factors (e.g., higher doses, obesity). Data show that the effect of daptomycin on rhabdomyolysis is cumulative and not immediate, with elevations typically occurring after 7 to 10 days of daptomycin therapy; however, CK elevations after 2 to 3 doses have also been reported. As such, administration of just the first daptomycin dose in the setting of elevated CK is generally unlikely to cause harm, but caution in proper dosing and routine laboratory and clinical monitoring should still be practiced.
Background

Rhabdomyolysis is reported to be an uncommon serious adverse effect reported with daptomycin use. It can be life-threatening in severe cases and lead to renal failure depending on the severity of muscle damage. Creatinine phosphokinase (CPK) is recommended as the monitoring parameter for probable rhabdomyolysis during daptomycin therapy. While most cases describe the onset of symptoms and CPK elevation to occur within seven to ten days of starting daptomycin, there are many cases that describe early onset muscle pain with CPK elevations after two to three doses. In general, frequent monitoring of CPK is necessary for early diagnosis of such complications. One case report describes weekly CPK monitoring, which mirrors the prescribing information recommendation. In general, the risk of rhabdomyolysis with daptomycin increases with higher doses (8 mg/kg/day) compared to the standard dose (6 mg/kg/day) and in patients who had dose intervals shorter than 24 hours. The risk of rhabdomyolysis also increases in patients with baseline renal impairment, concomitant statin use, and obesity. The mechanism of daptomycin-related rhabdomyolysis has been attributed to its pharmacology as it binds to the skeletal muscle cell membrane, causing membrane disruption, leakage of creatine kinase affected myofibers, and cell death. [1], [2]

A 2022 combined meta-analysis of 7 observational studies with a U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) disproportionality analysis (N= 4548), and a 2022 systematic review and meta-analysis of 16 observational studies (N= 6614) assessed whether concomitant statins increase daptomycin-associated musculoskeletal toxicity. In the 2022 combined analysis, statins increased odds of experiencing rhabdomyolysis (odds ratio [OR] 3.83; 95% confidence interval [CI] 1.43 to 10.26) but not myopathy (OR 1.72; 95% CI 0.95 to 3.12); the FAERS component of this mixed study reported OR 5.69 for myopathy and OR 5.77 for rhabdomyolysis. The 2022 meta-analysis found more CPK elevation exceeding the ULN with statins (OR 2.55; 95% CI 1.78 to 3.64) and CPK ≥5× ULN (OR 1.89; 95% CI 1.06 to 3.35), and more rhabdomyolysis (OR 11.60; 95% CI 1.81 to 74.37). Baseline CPK appeared only indirectly: one included cohort identified it as a risk factor, and every study carried high confounding risk partly because adjustments for baseline CPK were not conducted. Neither study, however, evaluated clinical or safety effects associated with withholding the first daptomycin dose pending baseline CPK results. [3], [4]

Background References: [1] Mettwali H, Elder K. Dose-independent daptomycin associated rhabdomyolysis: Case report. J Basic Clin Pharma October-2018;9(3): 286-288.
[2] Abdelnabi M, Leelaviwat N, Liao ED, Motamedi S, Pangkanon W, Nugent K. Daptomycin-induced rhabdomyolysis complicated with acute gouty arthritis. Am J Med Sci. 2023;365(5):450-456. doi:10.1016/j.amjms.2023.01.005
[3] Samura M, Takada K, Hirose N, et al. Incidence of elevated creatine phosphokinase between daptomycin alone and concomitant daptomycin and statins: A systematic review and meta-analysis. Br J Clin Pharmacol. 2022;88(5):1985-1998. doi:10.1111/bcp.15172
[4] Chuma M, Nakamoto A, Bando T, et al. Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis. Clin Infect Dis. 2022;75(8):1416-1422. doi:10.1093/cid/ciac128
Relevant Prescribing Information

Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), has been reported with the use of daptomycin. Rhabdomyolysis, with or without acute renal failure, has been reported. [5]

Patients receiving daptomycin should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. In patients who receive daptomycin, CPK levels should be monitored weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment with daptomycin. In adult patients with renal impairment, both renal function and CPK should be monitored more frequently than once weekly. [5]

In Phase 1 studies and Phase 2 clinical trials in adults, CPK elevations appeared to be more frequent when daptomycin was dosed more than once daily. Therefore, daptomycin should not be dosed more frequently than once a day. Daptomycin should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels >1,000 U/L (~5× ULN), and in patients without reported symptoms who have marked elevations in CPK, with levels >2,000 U/L (≥10× ULN). In addition, consideration should be given to suspending agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors, temporarily in patients receiving daptomycin. [5]

Relevant Prescribing Information References: [5] Daptomycin injection. Prescribing information. Aspiro Pharma Limited; 2023.
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Is it clinically meaningful to wait for a CK level to return before giving first dose of daptomycin?

Level of evidence

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


Please see Tables 1-5 for your response.

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors
Design

Multicenter, retrospective, observational study

N= 220
Objective To determine the safety of coadministration of daptomycin with statin therapy among hospitalized patients
Study Groups

Daptomycin with statins (n= 49)

Daptomycin alone (n= 171)
Inclusion Criteria Patients ≥18 years of age hospitalized who received daptomycin for a minimum of 7 days with concurrent statin therapy for at least 24 h
Exclusion Criteria Not specified
Methods Data collection from medical records and standardized case report forms. Creatinine phosphokinase (CPK) monitoring was at the discretion of the treating clinician. CPKs were considered baseline from 1 month prior to the day of initiation of daptomycin therapy. Logistic regression models were used to predict adverse events.
Duration January 2005 to May 2010
Outcome Measures

Incidence of serum CPK levels ≥1,000 U/liter, documented myalgias or muscle pains, discontinuation of therapy due to increased serum CPK levels
Baseline Characteristics   Daptomycin and statin (n= 49) Daptomycin only (n= 171)
Age (mean ± SD) (yr) 63.02 ± 13.14 56.50 ± 16.70
Male 30 (61.22%) 110 (64.33%)
Race - Caucasian 37 (75.51%) 113 (66.08%)
Race - African American 11 (22.44%) 49 (28.65%)
Body mass index 18.5–24.9 kg/m2 5 (10.20%) 45 (26.32%)
Body mass index 25.0–29.9 kg/m2 9 (18.37%) 35 (20.47%)
Body mass index 30–34.99 kg/m2 10 (20.41%) 29 (16.96%)
Body mass index 35–39.99 kg/m2 12 (24.49%) 26 (15.20%)
Body mass index ≥40 kg/m2 13 (26.53%) 36 (21.05%)
Creatinine clearance (mean ± SD) (mL/min) 70.47 ± 47.21 86.52 ± 57.81
Weight (mean ± SD) (kg) 105.80 ± 25.82 99.01 ± 33.96
Daptomycin absolute dose (mean ± SD) (mg) 706.20 ± 198.20 641.50 ± 189.40
Daptomycin dose (mean ± SD) (mg/kg) 6.78 ± 1.33 6.75 ± 1.54

Statin

Atorvastatin

Simvastatin

Pravastatin

Rosuvastatin

Lovastatin

Unknown

 

14 (28.57%)

22 (44.9%)

7 (14.29%)

3 (6.12%)

2 (4.08%)

1 (2.04%)

 

-

-

-

-

-

-
Results   Daptomycin and statin (n= 49) Daptomycin only (n= 171) p-value
CPK ≥1,000 U/liter 5 (10.20%) 9 (5.26%) 0.3152
Presence of myalgias/muscle pains 3 (6.12%) 5 (2.92%) 0.3809
Patients requiring discontinuation of therapy due to musculoskeletal toxicity 3 (6.12%) 6 (3.51%) 0.4205

The unadjusted logistic regression analysis showed that compared to patients using daptomycin alone, those using both daptomycin and statin were associated with 2.05 times the risk of experiencing musculoskeletal side effects (OR 2.05; 95% CI 0.65 to 6.41). Results were similar after controlling for potential confounders. 

There was no statistically significant association (OR 4.60; 95% CI 0.47  to 44.60) between experiencing CPK elevations with high (≥40mg) vs low statin (<40 mg) doses. Similar results were obtained for lower daptomycin doses (~4mg/kg) (OR 2.84; 95% CI 0.84 to 9.60).
Adverse Events Overall musculoskeletal toxicity was numerically higher in the combination group but not statistically significant. Myalgias were noted in 6.1% of patients receiving combination therapy compared to 2.9% receiving daptomycin alone. CPK elevations >1,000 U/liter occurred in 10.2% of the combination group compared to 5.3% in the daptomycin-alone group.
Study Author Conclusions Concomitant administration of daptomycin and statin therapy was associated with higher rates of CPK elevation and myalgias, but these were not statistically significant. Statin therapy should not prevent the use of daptomycin when clinically indicated.
Critique The study's retrospective design limits the ability to establish causality. The sample size may not be sufficient to detect rare events, leading to potential type II error. The study did not assess the impact of other myotoxic drugs or baseline CPK levels for all patients nor did it stratfiy its findings by baseline CPK at the initiation of daptomycin therapy. The reference agent for the high vs low statin dose definition was not reported in the study (presumed to be simvastatin as the most commonly studied coadministered statin, but this was not confirmed in the study). Despite these limitations, the study provides valuable insights into the safety of daptomycin and statin coadministration.
Table 1 References:
[6] Bland CM, Bookstaver PB, Lu ZK, Dunn BL, Rumley KF; Southeastern Research Group Endeavor (SERGE-45). Musculoskeletal safety outcomes of patients receiving daptomycin with HMG-CoA reductase inhibitors. Antimicrob Agents Chemother. 2014;58(10):5726-5731. doi:10.1128/AAC.02910-14

 

Safety of High-Dose Daptomycin in Patients With Severe Renal Impairment

Design

Retrospective, single-center cohort study in Taiwan

N= 164

Objective

To evaluate the safety of daptomycin in patients with severe renal impairment

Study Groups

High dose (≥9 mg/kg) (n= 37)

Standard dose (<9 mg/kg) (n= 127)

Inclusion Criteria

Adults treated with daptomycin at National Taiwan University Hospital with severe renal impairment (defined as creatinine clearance [CrCl] <30 mL/min or receipt of renal replacement therapy [RRT])

Exclusion Criteria

Incomplete medical records, daptomycin treatment duration <3 days; patients whose creatinine kinase (CK) elevation was attributed mainly to surgery, trauma, or seizure were excluded from the safety analysis

Methods

Retrospective electronic medical record review using a standardized case report form. The high dose daptomycin definition (≥9 mg/kg) vs standard dose (<9 mg/kg) was adapted from a prior study in the same hospital system that associated ≥9 mg/kg/day with better survival in vancomycin-resistant enterococcal (VRE) bacteremia. Dosing frequencies were every 24 hours, every 48 hours, or three times weekly with dialysis. CK elevation was defined as CK >1,000 U/L during daptomycin therapy; attribution to daptomycin was judged by two clinical pharmacists. Patients with no CK measured during treatment were assumed to have no CK elevation. Treatment success was defined as resolution of clinical signs and symptoms, no need for additional antibiotic therapy, and documented pathogen eradication at end of therapy.

Duration

January 2013 to June 2016

Outcome Measures

Primary: percentage of patients with CK elevation (>1,000 U/L)

Secondary: mean daptomycin dose in patients with vs without CK elevation, factors independently associated with CK elevation (multivariate analysis), treatment success in patients with bloodstream infections

Baseline Characteristics

  

High dose

(n=37)

Standard dose

(n=127)

p-value

Mean age, years

68.3 ± 15.5

68.0 ± 16.8

0.937

Male

20 (54.1)

67 (52.8)

0.889

Mean body weight, kg

53.2 ± 10.2

60.0 ± 12.0

<0.001

Obesity

1 (2.7)

9 (7.4)

0.459

Intensive care unit admission

23 (62.2)

84 (66.1)

0.655

CrCl <30 mL/min (no RRT)

6 (16.2)

21 (16.5)

0.963

Dialysis

25 (67.6)

76 (59.8)

0.395

Continuous renal replacement therapy (CRRT)

0

13 (10.2)

0.042

Acute kidney injury (AKI)

6 (16.2)

17 (13.4)

0.663

Mean daptomycin dose, mg/kg

10.8 ± 2.5

7.1 ± 1.4

<0.001

Dosing frequency: once daily / every 48 hours / three times weekly

6 (16.2) / 29 (78.4) / 2 (5.4)

7 (5.5) / 100 (78.7) / 20 (15.7)

0.076 / 0.962 / 0.168

Bloodstream infection

27 (73.0)

64 (50.4)

0.015

Prior antibiotic use

30 (81.1)

75 (59.1)

0.014

Concurrent statin, fibrate, or colchicine

3 (8.1)

12 (9.4)

1.000

CK followed during therapy

25 (67.6)

83 (65.4)

0.803

Mean CK measurements per week

0.7 ± 0.8

0.8 ± 1.3

0.946

Results

  

High dose

(n=37)

Standard dose

(n=127)

p-value

CK elevation >1,000 U/L

4 (10.8)

2 (1.6)

0.025

CK elevation, excluding patients without CK measured

16.0%

2.4%

0.025

Endpoint

CK elevation

(n=6)

No CK elevation

(n=158)

p-value

Mean daptomycin dose, mg/kg

9.3 ± 1.2

7.9 ± 2.3

0.034

Baseline CK levels in the 6 patients with CK elevations ranged from 10 to 53 U/L.

Multivariate analysis: High-dose daptomycin was the only factor independently associated with CK elevation (OR 7.46; 95% CI 1.22 to 45.69; p= 0.03).

CK elevation by dosing frequency: once daily 1/13 (7.7%), every 48 hours 5/129 (3.9%), three times weekly 0/22 (0%); p= 0.484.

CK elevation by concurrent statin, fibrate, or colchicine: 1/15 (6.7%) with vs 5/149 (3.4%) without; p=0.443.

Patients with CK elevation (n= 6): baseline CK 10–53 U/L (not measured in 1 patient); peak CK 1,299–4,697 U/L; onset during courses of 7–31 days; 4 of 6 received ≥9 mg/kg and 5 of 6 received every 48 hours dosing.

Treatment success, bloodstream infection (n=91): 51.6% overall; 60.9% for monomicrobial MRSA and 40.6% for monomicrobial VRE (not reported by dose group).

Adverse Events

CK elevation >1,000 U/L in 6/164 (3.7%) overall (high dose 4/37 [10.8%] vs standard dose 2/127 [1.6%]); muscle symptoms (muscle soreness or myalgia) in 3 of the 6 patients; symptoms could not be assessed in 2 patients due to intubation/poor consciousness. Rhabdomyolysis was not specifically reported. CK elevations resolved in all 6 patients.

Study Author Conclusions

In patients with severe renal impairment, high dose (≥9 mg/kg) daptomycin therapy may result in a significantly higher incidence of CK elevation. More frequent CK monitoring is warranted to avoid potential harm in this population.

Critique

This study provides real-world safety data for high-dose daptomycin in a population that is mostly on RRT and largely excluded from trials, but it is limited by its retrospective design, only 6 CK elevation events, lack of daptomycin serum concentrations, and the assumption that the 34.1% of patients without CK measured had no elevation, which likely underestimates incidence. All CK elevations occurred during therapy in patients whose baseline CK was normal or unmeasured, supporting ongoing (more than weekly) CK monitoring during high-dose therapy in severe renal impairment rather than reliance on the baseline value alone. Time to CK elevations was not reported, nor were CK elevations correlated to baseline CK elevation prior to initiation of daptomycin therapy despite all patients who experienced CK elevations having normal CK at baseline.
Table 2 References:
[7] Tai CH, Shao CH, Chen CY, Lin SW, Wu CC. Safety of high-dose daptomycin in patients with severe renal impairment. Ther Clin Risk Manag. 2018 Mar 13;14:493-499. doi:10.2147/TCRM.S159587

A Retrospective Multisite Case-Control Series of Concomitant Use of Daptomycin and Statins and the Effect on Creatine Phosphokinase
Design

Multicenter, retrospective, case-control study

N= 3658
Objective To evaluate the risk of creatinine phosphokinase (CPK) elevation in concomitant use of daptomycin and statins compared to daptomycin alone
Study Groups

Daptomycin alone (n= 2787)

Daptomycin + statin (n= 871)
Inclusion Criteria Adult patients 18 years and older who had been on daptomycin for over 72 hours, as either inpatients or outpatients, and patients who received multiple courses of daptomycin
Exclusion Criteria Patients with baseline elevated CPK, missing follow-up CPKs, or did not have at least 2 CPKs completed during therapy
Methods Patients were identified by electronic health records of daptomycin pharmacy administration codes. CPK elevation was defined as elevation at 5 times the upper normal limit (>1000 U/L). Logistic regression was used to analyze data, controlling for sex, race, BMI, and other risk factors.
Duration April 2004 to April 2016
Outcome Measures

Primary: Incidence of CPK elevation

Secondary: Hazard ratio for CPK elevation, adjusted for potential risk factors
Baseline Characteristics   Daptomycin group (n= 2787) Concurrent statin group (n= 871) p-value
Age, mean, (standard deviation) 59.2 (16.3) 66.2 (12.7) <0.001
Male, n (%) 1346 (48.5%) 478 (54.9%) 0.001
Race - Caucasian 2147 (77%) 662 (76%)  
Race - African American 496 (17.8%) 177 (20.3%)  
Race - Other 144 (5.2%) 32 (3.7%)  
Elevated body mass index (%) 448 (16.1%) 183 (21.0%) 0.001
Transplant (%) 100 (3.6%) 9 (1.0%) <0.001
Surgery (%) 1528 (54.8%) 474 (54.4%) 0.834
Diabetes (%) 823 (29.5%) 431 (49.5%) <0.001
Cancer (%) 1043 (37.4%) 264 (30.3%) <0.001
Myocardial infarction (%) 103 (3.7%) 103 (11.8%) <0.001
Chronic kidney disease (%) 1181 (42.2%) 454 (52.1%) <.001
Myalgia (%) 191 (6.9%) 56 (6.4%) 0.663
Rhabdomyolysis (%) 0 (0%) 0 (0%) 1.00
Baseline creatine phosphokinase (%) 2255 (80.9%) 709 (81.4%) 0.748
Elevated peak CPK (%) 90 (3.2%) 26 (3%) 0.236
Of the 871 patients receiving statins (in addition to daptomycin), 370 (42.5%) received atorvastatin, 238 (27.3%) re ceived simvastatin, 180 (20.7%) received pravastatin, 49 (5.6%) received rosuvastatin, 17 (1.95%) received lovastatin, and 17 (1.95%) others received other statins. Statins dose ranged from 5 mg to 80 mg daily, with a modular dose being 20 mg to 40 mg.
Results   Daptomycin alone (n= 2787) Daptomycin + statin (n= 871) p-value
Incidence of CPK elevation 90 (3.2%) 26 (3%) 0.85
Hazard ratio for CPK elevation 1.05  - 0.85
Adverse Events No instances of rhabdomyolysis were reported during the study period in patients on daptomycin therapy in either group.
Study Author Conclusions Concomitant use of daptomycin and statin did not show an increased risk of CPK elevation. Clinicians may consider concomitant use of daptomycin and statin therapy with weekly CPK monitoring.
Critique The study's retrospective design may lead to incomplete inclusion bias and potential missing values due to uncontrolled frequency and timing of CPK lab draws. However, it is the largest series evaluating CPK elevations in patients on daptomycin and statins, conducted across different hospital settings, which enhances its generalizability.
Table 3 References:
[8] Lehman B, Neuner EA, Heh V, Isada C. A Retrospective Multisite Case-Control Series of Concomitant Use of Daptomycin and Statins and the Effect on Creatine Phosphokinase. Open Forum Infect Dis. 2019;6(11):ofz444. Published 2019 Nov 7. doi:10.1093/ofid/ofz444

Factors affecting creatine phosphokinase elevation during daptomycin therapy using a combination of machine learning and conventional methods
Design

Population-based, retrospective, observational cohort study

N= 706
Objective To identify independent factors affecting daptomycin-induced musculoskeletal toxicity using a combination of machine learning and conventional statistical methods
Study Groups All patients (N= 706)
Inclusion Criteria Adult patients who received daptomycin
Exclusion Criteria Duration of daptomycin therapy <3 days; baseline creatinine phosphokinase (CPK) values not measured; baseline CPK value >200 IU/L; CPK values not measured during daptomycin therapy; operation during daptomycin therapy; age <18 years; other missing values
Methods Multiple logistic regression analyses were performed to identify independent factors affecting CPK elevation. Decision tree analyses were used to detect combinations of factors that change CPK elevation risk. Two definitions of musculoskeletal toxicity were employed: elevation of CPK value more than twice from baseline and >200 IU/L, and >1000 IU/L
Duration October 2011 to December 2020
Outcome Measures

Primary: Factors affecting CPK elevation during daptomycin therapy

Secondary: Combination of risk factors that changes the risk of each CPK elevation by decision tree analysis; risk of CPK elevation between the combination of each statin and daptomycin
Baseline Characteristics   All patients (N= 706)
Age, median years (IQR) 74 (63–82)
Male 436 (61.8%)
Body weight, kg, median (IQR) 56.4 (47.6–65.7)
Estimated over body weight 47 (6.66%)
Results   All patients (N= 706)
CPK elevation >200 IU/L 83 (11.8%)
CPK elevation >1000 IU/L 17 (2.41%)
There were no significant baseline differences in statin agent use between patients with and without CPK elevation. However, in both CPK elevation groups, significantly more patients received hydrophobic statins.
Adverse Events Not specified
Study Author Conclusions This novel approach revealed new risk factors for CPK elevation. High-risk patients require frequent CPK monitoring.
Critique The study's retrospective design may limit the ability to detect all symptoms of musculoskeletal toxicity. The causal relationship between daptomycin and CPK elevation could not be fully assessed due to potential confounding factors. Additionally, the study was limited by the exclusion of many patients, which may affect the generalizability of the findings.
Table 4 References:
[9] Lehman B, Neuner EA, Heh V, Isada C. A Retrospective Multisite Case-Control Series of Concomitant Use of Daptomycin and Statins and the Effect on Creatine Phosphokinase. Open Forum Infect Dis. 2019;6(11):ofz444. Published 2019 Nov 7. doi:10.1093/ofid/ofz444

Incidence and risk factors for musculoskeletal adverse effects associated with daptomycin in patients receiving outpatient parenteral antimicrobial therapy
Design

Single-center, retrospective cohort study

N= 127
Objective To evaluate the incidence and risk factors for creatinine phosphokinase (CPK) elevation and musculoskeletal adverse effects in patients receiving daptomycin outpatient antimicrobial therapy (OPAT)
Study Groups All patients (N= 127)
Inclusion Criteria Patients 18 years or older receiving outpatient antibiotic monitoring for daptomycin with at least two documented CPK laboratory values
Exclusion Criteria Lack of follow-up CPK values
Methods Retrospective analysis of patients receiving daptomycin OPAT. Daptomycin dosed using adjusted body weight for patients with obesity. Standard weekly monitoring of complete blood count, complete metabolic panel, and CK was performed. Data collected from inpatient and outpatient EHRs and home antibiotic pharmacy consult database.
Duration July 1, 2016, to September 30, 2022
Outcome Measures

Primary: Incidence of CPK elevation >500 U/L

Secondary: CPK elevation >1,000 U/L or >2,000 U/L; development of myopathy, myalgia, or rhabdomyolysis; discontinuation of daptomycin therapy; hospital admission due to daptomycin-related adverse event
Baseline Characteristics   Total (N = 127) CPK > 500 (n = 15) CPK < 500 (n = 112) p-value
Male 70 (55.1%) 12 (80%) 58 (51.8%) 0.039
Age, years 56 (46–63) 58 (45–66) 55 (46–61.5) 0.400
Body mass index (BMI), kg/m2 28.2 (24–34.8) 27.1 (25.1–34.8) 28.6 (23.8–34.2) 0.872
Serum creatinine (SCr), mg/dL .9 (.6–1.3) 1.2 (.9–2.2) .8 (.6–1.2) 0.008
Creatine phosphokinase (CPK), U/L 38 (24.5–73) 57 (30–156) 36 (23–72) 0.073
Results   Total (N = 127) CPK > 500 (n = 15) CPK < 500 (n = 112) p-value
CPK>500 U/L 15 (11.8%)  - - -
Time-to-event, days 13 (9–16) -  - -
Development of rhabdomyolysis 5 (3.9%) 5 (33.3%) 0 (0%) <0.001
Daptomycin discontinuation 16 (12.6%) 12 (80%) 4 (3.6%) <0.001
Daptomycin-related hospital readmission 4 (3.1%) 4 (26.7%) 0 (0%) <0.001
Adverse Events CPK elevation greater than 500 U/L (11.8%), myopathy or myalgia (5.5%), rhabdomyolysis (3.9%), hospital readmission due to rhabdomyolysis (3.1%).
Study Author Conclusions The incidence of CPK elevation was similar to previously reported rates. This study supports weekly lab monitoring for patients on higher doses of daptomycin in the OPAT setting.
Critique The study provides valuable insights into the incidence and risk factors for CPK elevation in patients receiving daptomycin OPAT. However, its retrospective design and single-center nature may limit generalizability. The reliance on patient-reported outcomes and physician documentation could lead to underreporting of adverse events. Further studies are needed to confirm these findings and explore additional risk factors.
Table 5 References:
[10] Wiley MB, Bennett KK, Siegrist EA, Neely SB, Sassine J, White BP. Incidence and risk factors for musculoskeletal adverse effects associated with daptomycin in patients receiving outpatient parenteral antimicrobial therapy. Antimicrob Steward Healthc Epidemiol. 2025 Jul 31;5(1):e169. doi:10.1017/ash.2025.10087