Daptomycin - A Powerful Solution Against Bacteremia

Overview:

Daptomycin is an antimicrobial agent that has wide applications in the healthcare industry. The prime authority of the United States that is responsible for regulating medicines - the Food and Drug Administration (FDA), endorsed the use of Daptomycin for several forms of blood infections. These blood infections are generally coined by the medical term bacteremia. Apart from the FDA-approved applications, Daptomycin is also employed for various other infective conditions that develop in the human body. Its usage is not restricted to a specific age group of the population.

Drug Group:

Daptomycin falls under the group of cyclic lipopeptide antibiotics. It is a novel and promising class of antibiotics which is produced from natural products. It is proven to be effective against a wide range of gram-positive bacteria.

Available Doses and Dosage Forms:

• Dosage Forms: Daptomycin is preferred to be given via veins in the form of intravenous shots or infusion. It is marketed in powder and liquid form, which can be reconstituted to form the injection liquid.

• Available Doses: The powder and liquid are mixed together such that the reconstituted mix can deliver 50 milligrams of Daptomycin per milliliter of the mix. The dosage of Daptomycin can be determined carefully considering the age of the patient, the stage of the infection, and the health status of the person.

For Patients:

What Is Bacteremia?

Bacteremia is a health condition where live and active bacteria that are capable of inducing infections propagate through the blood. These floating bacteria are free to establish an infection somewhere within the body. Routinely encountered bacteria include Staphylococcus aureus, Pneumococcus, Escherichia coli, group A Streptococcus, and Pseudomonas aeruginosa. Bacteremia, as such, is not life-threatening; however, once the floating bacteria establishes infections in the body, it can precipitate grave blood infections called septicemia. Bacteremia rarely poses challenges in healthy individuals, but in individuals with considerably compromised immunity, it easily precipitates septicemia and other associated complications. Urinary tract infections (UTI) and respiratory tract infections are the two potential sources that can induce the development of bacteremia. However, it is not restricted to these two infections. Any sort of infectious focus can lead to bacteremia. Even certain dental procedures do bring about bacteremia. However, those are generally brief and momentarily and get cleared off by the body. Antibiotics are the mainstay treatment for bacteremia, and the treatment is largely designed by considering the patient’s immune status.

How Does Daptomycin Work?

Daptomycin belongs to a specific category of antibiotic that works to contain bacterial infection. Daptomycin influences the functions of bacterial outer covering (cell membrane) by attaching to the outer envelope. Once the cell membrane activities are remarkably hampered, it reflects in the internal processes in the bacterial cells. The synthesis of necessary proteins and genetic material will also get interrupted, and eventually, it gives rise to the death of the bacterial cells.

How Effective Is Daptomycin?

Daptomycin therapy is initiated to tackle bacteremia and to get the blood cleared of bacteria. If bacteremia is left unattended, it can then progress into septicemia and can endanger the person’s life. Daptomycin works to kill the live bacteria floating in the blood. It is effective for both adults and younger populations over one year of age. Studies have proven the efficacy of Daptomycin in settling various complex bacterial skin infections and bacteremia induced by Staphylococcus aureus bacterial species. However, it is not advisable for other infections like pneumonia (pus gathering in the lung tissues).

What Are the Things to Inform the Doctor Before Taking the Drug?

• Certain patients might have a history of reaction towards Daptomycin or related medicines. Individuals who have had a prior encounter with the medicine should report the undesired events to the concerned doctor. In case the patient encounters sudden allergic symptoms following Daptomycin administration, it necessitates instantaneous medical attention.

• The doctor should be made aware of all other ailments that the patient suffers before initiating Daptomycin therapy. In addition, the details of concomitant medications should be discussed with the doctor to ensure the safe administration of Daptomycin and to prevent unexpected drug-to-drug reactions.

• Pregnant patients should keep their doctor updated regarding pregnancy because whatever medicines are taken during pregnancy carry the risk of influencing the growth and development of the child in the womb. To ensure the safety of the developing child, pregnancy status should be informed without fail before starting the treatment. If the patient undergoing therapy with Daptomycin is detected to be pregnant, then seek the doctor's advice before continuing with the therapy.

How Is Daptomycin Administered?

Daptomycin is preferred to be administered to the patient's body via a vein. It can be either in the form of an injection or infusion (controlled and restricted delivery of medicinal fluid into the circulation). The availability of the drug following oral intake is considerably less, and hence it is not advised to be taken orally. In intravenous infusion, 0.9 percent saline solution is used as the medium for infusion.

What Are the Side Effects of Daptomycin?

There are certain adverse effects associated with the administration of Daptomycin. Some of the frequently encountered side effects include the following:

• Muscle weakness and neurological issues, like tingling sensations in the legs and arms, are some of the notable side effects of Daptomycin.

• Daptomycin is known to induce allergic reactions at the point of injection. It is often accompanied by mild swelling and erythema (redness).

• An unreasonable hike in body weight and gastrointestinal issues, like stomach aches and diarrhea with blood streaks, are the routinely elicited side effects of Daptomycin.

• In addition, Daptomycin also induces lingering headaches, fatigue, and dizziness (vertigo). The person experiences trouble in attaining deep sleep.

• Certain patients are reported to have skin reactions in the form of tiny blisters (bleb-like projections) and rashes. Some patients do develop associated itching over the skin, which can be irritating and troubling.

• Patients may experience a frequent tendency to urinate, which is often coupled with a burning sensation. The urine color also gets altered and attains an abnormally dark color.

• Chest pain, strenuous breathing, short breaths, and a puffy face are some of the critical effects of Daptomycin.

• Fever, chills, cough, throat pain, urinary infections, and other signs of infection are also reported with Daptomycin therapy.

Missed Dose:

The chance of missing a dose is quite rare, as Daptomycin is given as shots or infusions in hospital settings. However, if the patient fails to get administered Daptomycin while under therapy, get the medicine as soon as possible to ensure sufficient drug concentration in the blood to deal with the bacteremia.

Overdose:

Daptomycin overdosage requires prompt treatment to get the blood cleared off the heavy medicine load. Dialysis (kidney function carried out with the help of external equipment) will be initiated to deal with the overdose concentration in the bloodstream. However, the rate of Daptomycin elimination is remarkably low, which is compensated by using a high-flux membrane (filter with larger pores) for dialysis.

Storage:

Daptomycin is advised to be stored in powder form under 68 to 77 degrees Fahrenheit. The medicine should be reconstituted during the time of injection or infusion. The reconstituted form is not preferred to be stored for longer periods. The powder form comes in a vial of 10-milliliter capacity, and the powder accounts for 500 milligrams of the medicine.

For Doctors:

Indications:

FDA endorsed the following indications for Daptomycin:

• Bacteremia (blood infection induced by Staphylococcus aureus).

• Complicated skin and skin structure infections (cSSSI).

• Bacteremia encompassing right-sided infective endocarditis (triggered by Methicillin-resistant and Methicillin-susceptible bacterial isolates).

In addition to the above-given indications, Daptomycin is also employed for various other ailments as off-label medicine (not endorsed by FDA). Some of the off-label uses include the following:

• Diabetic foot.

• Septic arthritis.

• Vancomycin-resistant enterococcal (VRE) infections.

• Intracranial abscess.

• Staphylococci or enterococci-induced prosthetic joint infections.

• Osteomyelitis.

• Cerebrospinal fluid (CSF) shunt infection.

Dose:

The dosage of Daptomycin varies with the condition for which it is administered, health status, and age of the person.

1. Bacteremia: For adult patients suffering from bacteremia, intravenous administration of Daptomycin in the form of injection is advised. The recommended daily dose is 6 mg per kg (milligram per kilogram) of body weight. The treatment period ranges from two to six weeks, depending on the severity of the blood infection.

2. Complicated Skin and Skin Structure Infections: For adult patients with cSSSI, 4 milligrams (mg) of Daptomycin per kilogram (kg) of body weight is advised to be given once daily for a period of one or two weeks. It can be given as either injection or infusion. Injection should be given over two minutes, while the infusion is given for half an hour.

In the case of pediatric patients under the age category of 1 to 17 years, intravenous infusion is advised either for half an hour or one hour period. Infusion over one hour is recommended for children under one to seven age category, and for the rest of the pediatric patients, infusion over half an hour is preferred. The daily dosage regimen for pediatric patients under 12 to 17 years is 5 mg per kg; for 7 to 11 years is 7 mg per kg; for 2 to 6 years is 9 mg per kg; and for 1 to 2 is 10 mg per kg.

Dosing Considerations:

The dosage of Daptomycin should be modified in case the patient has impaired kidney function. In patients with collapsed creatinine clearance, Daptomycin administration is given once in two days only.

What Are the Pharmacological Actions of Daptomycin?

• Mechanism of Action: Daptomycin is bactericidal in function. Upon encounter with specific bacteria, Daptomycin attaches to the bacterial cytoplasmic membrane. Following this, the membrane potential undergoes sudden depolarization. This collapse in the membrane potential remarkably impacts bacterial cellular functions, like protein and nucleic acid synthesis. Impaired functions in the bacterial cell eventually contribute to the death of the bacteria. In this way, Daptomycin gears down the active bacterial count in the skin and blood.

• Pharmacodynamics: Daptomycin works effectively against several gram-positive bacteria like Staphylococcus aureus, Streptococcus species, vancomycin-resistant Enterococci, and Clostridium perfringens. The bactericidal activity of Daptomycin is directly proportional to the concentration of the drug in the bloodstream. As it is intravenously introduced into the bloodstream, the drug action is initiated promptly without much delay.

• Pharmacokinetics: Once Daptomycin is directly infused into the circulation, the drug molecules attach to certain plasma proteins, particularly albumin. There is only limited information regarding metabolism. Unlike other medicines, Daptomycin is not chiefly processed by liver enzymes. However, certain studies have figured out negligible concentrations of Daptomycin metabolites following intravenous administration. The elimination of Daptomycin is carried out by the kidneys via urine and feces. A larger proportion of Daptomycin is eliminated through urine.

Toxicity:

There are no scientific reports available concerning the toxicity of Daptomycin. Certain non-clinical studies have proven that Daptomycin holds no potential for carcinogenesis or mutagenesis in animals. It was found that the fertility of the animals remains unaffected with Daptomycin therapy.

Clinical Studies:

Clinical studies were conducted to analyze the effectiveness of Daptomycin in dealing with bacteremia by comparing it with a standard drug (Vancomycin, Gentamicin, Oxacillin). The study could not demonstrate an appreciable difference in effectiveness and points out that Daptomycin is an equally effective alternative medicine for bacteremia. The study has also concluded that the time taken by Daptomycin therapy to tackle bacteremia is more or less comparable with the standard medicines.

What Are the Contraindications of Daptomycin?

• Prior experience of allergy or reaction, or hypersensitivity upon exposure to Daptomycin or other related medicine is an obvious contraindication for Daptomycin therapy.

• Geriatric patients with considerable impairment in kidney functions are prone to develop Daptomycin toxicity issues even with normal dosage.

Warnings and Precautions:

• Anaphylaxis: Exaggerated allergic reactions are reported with the administration of Daptomycin, and hence the patient should be closely monitored for signs of hypersensitivity reactions. In the event of allergic reactions, the Daptomycin therapy should be discontinued with immediate effect. These reactions are potentially dangerous and entail immediate medical assistance to safeguard the patient’s life.

• Eosinophilic Pneumonia: Certain study reports concluded the association of Daptomycin with eosinophilic pneumonia. Two to four weeks of Daptomycin therapy often precipitates manifestations like fever, diffuse pulmonary infiltrates, hypoxic respiratory insufficiency, dyspnea, organizing pneumonia, and other potential lung diseases. The respiratory condition exhibited dramatic improvement upon stoppage of Daptomycin.

• Myopathy: Daptomycin can trigger weakness and sores in the muscles due to an upliftment in the creatinine phosphokinase level (CPK) in the body. Hence periodic monitoring of kidney functions and enzyme levels should be carried out to keep track of other possible complications of Daptomycin. Nonclinical studies have concluded an increased susceptibility of muscular issues in the younger population rather than the adult population following Daptomycin therapy. The development of myopathy is closely linked with dosage frequency. Hence it is advised to restrict the frequency to once a day. In addition to myopathy, rhabdomyolysis is also occasionally reported following Daptomycin therapy.

• Peripheral Neuropathy: Post-marketing surveillance of Daptomycin revealed certain neurological issues like peripheral neuropathy following the therapy. Hence doctors are advised to look for manifestations of peripheral neuropathy in patients undergoing Daptomycin therapy.

• Clostridium Difficile-Associated Diarrhea: Daptomycin, being antimicrobial, modifies the healthy microbial colony that is normally present in the human body. It eventually results in the preferential exacerbation of a specific microbe called Clostridium difficile. This overgrowth eventually brings about Clostridium difficile-associated diarrhea (CDAD).

• Compromised Efficacy: The efficiency of Daptomycin gets partially compromised in patients with remarkably impaired kidney functions. As a result, the anticipated response toward Daptomycin cannot be achieved in such patients. Therefore, the renal status of the patient should be assessed beforehand to ensure the effectiveness of the medicine.

• Bacteremia Relapse: At times, even after Daptomycin therapy, the bacteremia persists, and it primarily indicates the non-responsiveness of the bacteria towards Daptomycin. It is frequently encountered upon bacterial resistance to Daptomycin. In such cases, blood cultures and sensitivity should be tested to identify the susceptible medicine for the condition, and the treatment should be modified accordingly.

What Are the Drug Interactions of Daptomycin?

Simultaneous administration of Daptomycin and hydroxymethylglutaryl coenzyme A (HMG Co-A) reductase inhibitors enhance the chance of developing myopathy. Statins raise the CPK level, which, when combined with Daptomycin, amplifies the CPK level further. It eventually potentiates muscular toxicity.

Specific Considerations:

• Daptomycin During Pregnancy: There is no specific study report published for the guidance of administration of Daptomycin in pregnant ladies. Though the non-clinical studies could not reflect any birth defects in the developing fetus, Daptomycin administration is routinely restricted during pregnancy.

• Daptomycin During Breastfeeding: Any drug that is administered to lactating women poses challenges in milk production and bears the risk of passing the medicine into the child through breast milk. Certain studies have concluded that 0.1 percent of the total dose that is administered to the lactating mother gets into the breastfed child. Hence, Daptomycin is generally not recommended during breastfeeding.