Daptomycin has the activity against gram positive bacteria causing skin and skin structure infections (SSTIs), bacteremia, right-sided infective endocarditis. This drug is reserved as alternative treatment for infections caused by methicillin-resistant Staphylococcus aureus.
 

Objective: The purpose of this study was to determine whether daptomycin use at a community hospital met the current evidence-based clinical guideline.
 

Keywords: Daptomycin; Vancomycin; MRSA; Sstis. 

Design/Setting/Patients/Intervention/Main Outcome/Results/Conclusions

The study was a retrospective descriptive patient chart review from January 1 to June 27, 2014. Patients were excluded if they did not meet the age requirements. The following data were reviewed: patient age, past medical history, antibiotic regimen, result value from microbial organisms and chemistry lab, indication of antibiotic, and provider’s note. Creatinine clearance (CrCl) was calculated by Cockcroft-Gault formula. To maintain the confidentiality, all data were recorded without patient identification. If patient was on vancomycin less than 1 day, it was considered as an incomplete dosing regimen. All the data were evaluated with MRSA infection and skin and soft tissue infections clinical practice guidelines by the Infectious Diseases Society of America (ISDA). 70 patients received the medication with 8% for off-label indications. The ISDA guideline recommends dose for osteomyelitis is 6mg/kg. Two patients were treated with 7mg/kg and 8mg/kg was given to one patient. Poor renal function may be the reason for choosing daptomycin over vancomycin due to less prevalence of the side effect. However, only 12% of patients had impaired renal function. The package insert recommends dosage adjustment based on renal function, such as, every 24 hour if CrCl > 39mL/min and every 48 hours if CrCl

Vancomycin has been used for many years in practice, but its’ effect on the kidneys and extensive monitoring can be limiting. Over the years, newer agents have come out such as daptomycin, tigecycline, linezolid, ceftaroline and telavancin which have been used as alternative agents. The use of these agents; however, can be limited in the community hospital due to cost and formulary issues. Therefore, it is important to evaluate that these agents are being used correctly for the appropriate indications to lower cost and to prevent unnecessary resistance. This is why this study is relevant to current practice to help us determine if daptomycin is being utilized properly and if not, how best to improve it. The next steps would be to study other drugs that are listed above to see if they are being utilized correctly and conduct and educational program for the hospital if they are not being utilized correctly.

                                  
3. Introduction and Objective, Limitations, Conclusion

Daptomycin is a cyclic lipopeptide bactericidal antibiotic approved by the Food and Drug Administration for the treatment of complicated skin and skin structure infections (cSSSI) and Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis. It is not indicated for the treatment of pneumonia because its activity is inhibited by pulmonary surfactant. [1] Daptomycin is also recognized as an alternative for the treatment of infections caused by vancomycin-resistant enterococci.[2,3]The proposed mechanism of action is a rapid depolarization of cell membrane potential via interfering with the integrity of bacterial cell wall structure, which results in bacterial cell death.[4]

Daptomycin is available as injection for intravenous (IV) use (Cubicin). The most common adverse effects include diarrhea (11.7%), vomiting (11.7%), and pain in throat (8.3%). Other serious adverse effects include rhadomyolysis, renal failure (2.2-3.3%), asthmatic and pulmonary eosinophilla (8.3%) [5].

Daptomycin’s usual dosage regimen is 4mg/kg once daily for complicated skin and skin structure infections (cSSSI) for 7 to 14 days and 6mg/kg once daily for S. aureus bacteremia for 2 to 6 weeks.[Package insert recommends dosage adjustment based on renal function, either every 24 hours if CrCl more than 30 mL/min or 48 hours if CrCl less than 30 mL/min.

The efficacy of daptomycin for treatment of cSSSI due to MRSA was demonstrated in a randomized trial demonstrating that the clinical success rate was similar to that of vancomycin, which is the standard of care for S. aureus bacteremia and right-side endocarditis. [6] The current practice guidelines for management of SSTIs recognize both vancomycin and daptomycin as empiric and defined therapies for purulent SSTIs. However, vancomycin is clearly defined as the drug of choice for treatment of SSTIs caused by MRSA. It also recommends initiating vancomycin until MRSA is ruled out for surgical site infections (SSIs) with indurations and erythema [7].

The development of resistance to daptomycin remains rare. Due to numerous daptomycin resistance reports and the unknown exact resistance mechanism, hospital P&T Committees often reserve the use of daptomycin for treatment of MRSA strains with vancomycin-resistance or vancomycin treatment failure to prevent possible bacterial resistance and preserve the utility[8-12].

The primary study objective was to determine whether daptomycin use met the current clinical guideline. The secondary objectives were as follows: to determine the number of patients who had failed previous therapy with vancomycin before switching to daptomycin or based on pharmacokinetic parameters or were not good candidates for vancomycin therapy, to quantify the frequency of administration of daptomycin, to describe the indication for which daptomycin was prescribed, to describe the dosage regimen, including doses based on mg/kg body weight and to determine whether the dosage interval was appropriate for patients according to their renal function.

The study is a retrospective descriptive patient chart review from January 1 to June 27, 2014. The study was exempt from IRB approval based on the hospital’s IRB policy for retrospective chart review of identity protected subjects. Eligible patients were at least 18 years of age and had received daptomycin at the hospital for bacterial infections, including skin and soft tissue infections (SSTIs), osteomyelitis, bacteremia, urinary tract infections (UTIs), and pneumonia. Patients were excluded if they did not meet the age requirements. The following data were reviewed: patient age, past medical history, antibiotic regimen, result value from microbial organisms and chemistry lab, indication for antibiotic, and providers’ note. Creatinine clearance (CrCl) was calculated by the Cockcroft Gault formula. To maintain confidentiality, all data was recorded without patient identification. If patient was on vancomycin less than 1 day, it was considered an incomplete dosing regimen. All data was evaluated for appropriateness using MRSA infection and SSTI clinical practice guidelines by the Infectious Diseases Society of America (IDSA).

Daptomycin was prescribed and administered for 70 patients during the study period.

Most patients (51 of 70) received daptomycin for skin and soft tissue infections, 7 out of 70 for osteomyelitis, 5 out of 70 for a urinary tract infection, 4 out of 70 for bacteremia and 3 out of 70 for pneumonia for which daptomycin is ineffective. Table 1 demonstrates the percentage of patients who received treatment for which indication. Twenty-one percent of patients received daptomycin for off-label indications. Table 2 discusses the dosages received by each patient and table 3 demonstrates the number of patients who had abnormal renal function. Table 4 shows how many patients had received vancomycin prior to receiving daptomycin. Descriptive statistics were used to analyze this data.

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Table 1:Number of daptomycin admissions on each disease state

 

Table 2: Dosages administered to each skin and soft tissue infection patient

 

Table 3: Number of patients who had either normal or abnormal renal function

The primary study objective was to determine whether daptomycin use met the current clinical guideline. Daptomycin was not always utilized correctly with the appropriate dosing from guidelines. The dosing for skin and soft tissue infections is 4 mg/kg once daily for 7 to 14 days according to the IDSA guidelines5, but three patients were treated with 8 mg/kg and eighteen patients were treated with 6 mg/kg based on provider preference and unknown reasons. The IDSA guidelines state the dose for osteomyelitis is 6 mg/kg, but two patients were given 7 mg/kg and one patient 8 mg/kg again for provider preference and unknown reasons. As mentioned in table 4, 31 patients were started on vancomycin before switching to daptomycin due to various reasons while 39 were not on vancomcyin prior to daptomycin for which reasons were not recorded. It was found that the frequency of administration of daptomycin is quite high and not always correctly in line with the guidelines. Daptomycin was used correctly for the right indications (i.e,, osteomyelitis, skin and soft tissue infections, UTI and bacteremia) except for the one time it was used for pneumonia. The dosages varied as discussed above and were not always in line with the guidelines for various reasons. The patients who had abnormal renal function (eight out of seventy) were given proper dosing according to the renal adjustment parameters in the package insert.

Future studies should focus on proper utilization of other agents which cover MRSA and looking into reasons behind why agent(s) are not utilized properly and how to better educate providers at the hospital.

Table 4: Number of vancomycin administration before daptomycin initiation

The biggest limitation of our study was the limited number of patients. Another limitation was the unknown reasons for choosing different doses of daptomycin which may not be in the guidelines and the variability of providers and ways of practicing. Also, progress notes were not always accurate and we had limited data as only half of the system is electronic and the other half is on paper charts.

In conclusion, we found that daptomycin is not always being utilized correctly according to the guidelines in some situations, but for the most part it is. This drug is recommended as an alternative treatment for MRSA infections by clinical guidelines and for antimicrobial stewarship purposes, including limiting resistance and availability of cost effective options. Due to numerous daptomycin resistance reports and the unknown exact resistance mechanism, hospital P&T Committees often reserve the use of daptomycin for treatment of MRSA strains with vancomycin-resistance or vancomycin treatment failure to prevent possible bacterial resistance and preserve the utility. This study will help us in further looking at the use of daptomycin when it is ordered and providing proper education to physicians and pharmacists. 

1. Silverman JA, Mortil LI,  Vanpraagh AD (2005) Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis 191:12:2149.

2. Mangili A, Bica I, Snydman DR, Hamer DH (2005) Daptomycin-resistant, methicillin-resistant Staphylococcus aureusbacteremia. Clin. Infect Dis 40:1058 -1060.

3. Vouillamoz J, Moreillon  P, Giddey M, Entenza JM (2006) Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci. J Antimicrob Chemother 58:1208-1214.

4. Cubicin, Lexington MA (2013) Cubist Pharmaceuticals.

5. Micromedex Healthcare series: DRUGDEX® System.

6. Fowler VG, Boucher, Helen W, Corey R, Abrutyn E, et al. (2006) Daptomycin versus standard therapy for bacteremia and endocarditis cause by Staphylococcus aureus. N Engl J Med 355:7:653

7. Stevens DL,  Bisno AL, Chambers HF, Dellinger EP, Ellie Goldstein  JC, et al. (2014) Practice guidelines for the diagnosis and management of skin and soft tissue infections: update by the infectious diseases society of America. Clin Infect Disl 15:59:2:147-59.

8. Bayer AS, Schneider T, Sahl HG (2013) Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall. Annals of NY Academy of Sciences 1277: 139-158.

9. Hayden MK, Rezai K, Hayes RA (2005) Development of daptomycin resistance in vivo in methicillin-resistant Staphlococcus aureus. J Clin Microbiol 43:5285-5287.

10. Lewis JS II, Owens A, Cadena J (2005) Emergence of daptomycin resistance in Enterococcus faecium during daptomycin therapy. Antimicrob. Agents Chemother  49:1664-1665.

11. Munoz-price LS, Lolans K Quinn JP (2005) Emergence of resistance to daptomycin during treatment of vancomycin-resistant Enterococcus faecalis infection. Clin Infect Dis 41:565-566.

12. Fox B, Bland SE (2011) UWHC Guidelines for the Use of Daptomycin (Cubicin). UWHC P&T Committee.