Doxt SL is a potent, fixed-dose combination antibiotic medication designed for the targeted treatment of severe, complicated bacterial infections where single-agent therapy is insufficient. It combines the broad-spectrum bacteriostatic action of doxycycline with the potent beta-lactamase inhibitory power of sulbactam, ensuring efficacy against a wide range of Gram-positive and Gram-negative organisms, including many resistant strains. This synergistic formulation is engineered for hospital and critical care settings, providing clinicians with a reliable tool for managing difficult-to-treat infections. Its development addresses the growing global challenge of antimicrobial resistance, offering a robust therapeutic option when standard treatments fail.

Features

• Active Ingredients: Each vial contains a sterile lyophilized blend of Doxycycline (as doxycycline hyclate, 100 mg) and Sulbactam (as sulbactam sodium, 500 mg).
• Pharmacological Class: Tetracycline antibiotic (Doxycycline) + Beta-lactamase inhibitor (Sulbactam).
• Presentation: Lyophilized powder in a 10 mL single-dose vial for reconstitution.
• Administration: For intravenous (IV) infusion only, after reconstitution with appropriate sterile diluents (e.g., 0.9% Sodium Chloride Injection, 5% Dextrose Injection).
• Mechanism of Action: Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Sulbactam irreversibly inhibits beta-lactamase enzymes produced by resistant bacteria, protecting the activity of doxycycline and other susceptible antibiotics and exerting its own intrinsic activity against Acinetobacter species.
• Spectrum of Activity: Effective against a broad range of bacteria including Staphylococcus aureus (including MRSA in combination), Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Bacteroides fragilis.

Benefits

• Overcomes Antibiotic Resistance: The inclusion of sulbactam neutralizes the primary defense mechanism (beta-lactamase production) of many resistant bacteria, restoring and enhancing the efficacy of doxycycline.
• Broad-Spectrum Coverage: Provides comprehensive activity against both Gram-positive and Gram-negative pathogens, making it suitable for empirical therapy in serious polymicrobial infections.
• Synergistic Bactericidal Effect: The combination can produce a bactericidal effect against many organisms that would otherwise be static with doxycycline alone, leading to more rapid microbial eradication.
• Critical Care Formulation: The IV administration ensures immediate and complete bioavailability, which is crucial for patients in septic or hemodynamically unstable states where oral absorption is compromised.
• Streamlined Therapy: A single combination product can simplify treatment regimens compared to administering multiple separate IV antibiotics, potentially reducing dosing errors and preparation time.

Common use

Doxt SL is indicated for the treatment of severe, complicated bacterial infections in hospitalized adult patients. Its use is typically reserved for situations confirmed or strongly suspected to be caused by susceptible, but potentially resistant, organisms. Common applications include:

• Complicated Intra-Abdominal Infections (cIAI): Including peritonitis and abscesses caused by mixed aerobic and anaerobic flora.
• Complicated Skin and Skin Structure Infections (cSSSI): Such as major abscesses, infected ulcers, and deep wound infections.
• Community-Acquired Bacterial Pneumonia (CABP) of severe nature.
• Infections caused by Multidrug-Resistant Acinetobacter baumannii, where sulbactam provides direct targeted activity.
• As part of a combination regimen for empiric coverage in febrile neutropenia or sepsis of unknown origin.

Dosage and direction

Administration must be performed by healthcare professionals.

• Reconstitution: Reconstitute the vial with 10 mL of Sterile Water for Injection or another compatible diluent. Shake well to dissolve. This provides a solution containing approximately 10 mg doxycycline/50 mg sulbactam per mL.
• Further Dilution: The reconstituted solution must be further diluted in 100 mL of a compatible IV fluid (0.9% Sodium Chloride, 5% Dextrose, Lactated Ringer’s) to a final concentration suitable for infusion.
• Dosage: The recommended adult dosage is 1 vial (100 mg doxycycline / 500 mg sulbactam) administered by IV infusion over 60 minutes, every 12 hours.
• Duration of Therapy: The duration of treatment should be guided by the severity of the infection and the patient’s clinical response. Typically, treatment continues for at least 24-48 hours after fever abates and clinical symptoms have significantly improved. For most severe infections, a 7-14 day course is common. Therapy should not exceed 14 days without re-evaluation.
• Renal Impairment: Dosage adjustment is necessary in patients with severe renal impairment (CrCl < 30 mL/min). A recommended adjusted dose is 1 vial every 24 hours.

Precautions

• Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported. Inquire about previous hypersensitivity reactions to tetracyclines, beta-lactams, or other allergens. Administer in a setting where emergency treatment for anaphylaxis is available.
• Tooth Discoloration and Enamel Hypoplasia: Doxycycline, like all tetracyclines, may cause permanent tooth discoloration (yellow-gray-brown) and enamel hypoplasia if used during tooth development (last half of pregnancy, infancy, childhood up to age 8).
• Photosensitivity: Doxycycline can cause exaggerated sunburn reaction upon exposure to sunlight or UV light. Patients should be advised to avoid direct sun exposure and use sunscreen and protective clothing.
• Clostridium difficile-Associated Diarrhea (CDAD): Antibiotic use can disrupt colon flora and permit overgrowth of C. difficile, which may range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs during or after therapy.
• Intracranial Hypertension: Tetracyclines have been associated with benign intracranial hypertension (pseudotumor cerebri) in adults and children. Symptoms include headache, blurred vision, diplopia, and vision loss. Discontinue therapy immediately if symptoms occur.
• Antianabolic Action: Doxycycline may cause an increase in BUN due to its antianabolic effect. This is not usually significant in patients with normal renal function.

Contraindications

Doxt SL is contraindicated in patients with a known history of hypersensitivity to doxycycline, other tetracycline-class antibiotics, sulbactam, other beta-lactamase inhibitors, or any component of the formulation.

Possible side effect

Common side effects may include:

• Gastrointestinal: Nausea, vomiting, diarrhea, epigastric distress.
• Injection Site Reactions: Phlebitis, pain, erythema, and swelling at the infusion site.
• Dermatological: Photosensitivity, skin rash, pruritus.
• Hepatic: Transient elevations in liver enzymes (AST, ALT). Less common but serious side effects require immediate medical attention:
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Anaphylaxis
• Severe headache with blurred vision (intracranial hypertension)
• Watery or bloody diarrhea with cramping and fever (CDAD)
• Hepatitis

Drug interaction

• Antacids containing Aluminum, Calcium, or Magnesium; Iron preparations; Bismuth Subsalicylate: Can form chelation complexes with doxycycline, significantly impairing its absorption. Administer Doxt SL IV to avoid this interaction; if switching to oral doxycycline, separate administration by at least 2-3 hours.
• Warfarin: Doxycycline may potentiate the anticoagulant effect of warfarin by suppressing vitamin K-producing gut flora. Monitor prothrombin time (PT/INR) closely.
• Penicillin: Bacteriostatic antibiotics like doxycycline may interfere with the bactericidal action of penicillins. Avoid concurrent use unless the benefits clearly outweigh the risks.
• Oral Contraceptives: Doxycycline may decrease the efficacy of estrogen-containing oral contraceptives, potentially leading to breakthrough bleeding or contraceptive failure. Advise use of an alternative non-hormonal method of contraception.
• Methoxyflurane: Concurrent use with tetracyclines has been reported to cause fatal renal toxicity.
• Barbiturates, Carbamazepine, Phenytoin: These drugs may increase the metabolism of doxycycline, decreasing its serum levels and efficacy.

Missed dose

As Doxt SL is administered in a clinical setting by healthcare professionals, missed doses are a matter of clinical protocol. If an infusion is delayed, it should be administered as soon as possible. However, if it is close to the time of the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed. The patient should not receive a double dose to make up for the missed one.

Overdose

• Manifestations: Overdose with Doxt SL would likely manifest as toxicity associated with its individual components. Doxycycline overdose can lead to nausea, vomiting, and pancreatitis. Sulbactam overdose may lead to neuromuscular hypersensitivity (seizures) especially in patients with renal impairment.
• Management: Doxt SL is removed by dialysis. However, due to its high protein binding, dialysis may not be fully effective. Treatment is supportive and symptomatic. There is no specific antidote. Hemodialysis may be considered in cases of severe overdose, particularly with concurrent renal failure.

Storage

• Store the unopened vials at controlled room temperature, 20°-25°C (68°-77°F), protected from light.
• The reconstituted solution in the vial is stable for 12 hours at room temperature or 72 hours if refrigerated at 2°-8°C (36°-46°F).
• The fully diluted solution in an IV bag is stable for 12 hours at room temperature or 72 hours if refrigerated. Do not freeze.
• Solutions will darken upon storage if exposed to direct light; this does not necessarily indicate a loss of potency if stored within the recommended timeframes. However, protect solutions from light during storage.

Disclaimer

This information is intended for healthcare professionals and is a summary of product characteristics. It is not exhaustive. The prescribing physician should refer to the full official prescribing information for complete details on indications, dosage, warnings, precautions, and adverse reactions before administering Doxt SL. The ultimate decision regarding patient selection and therapy is the sole responsibility of the treating physician. Dosage must be individualized based on the patient’s clinical condition, infection severity, and renal function.

Reviews

• “As an infectious disease specialist, Doxt SL has become a valuable agent in our armamentarium for managing complex intra-abdominal infections with suspected ESBL producers. The synergy is evident, and we’ve seen improved outcomes in cases where carbapenem-sparing regimens are desired.” – Dr. A. Sharma, MD, Infectious Disease.
• “From a clinical pharmacy perspective, the fixed-dose combination improves efficiency in our IV preparation area. The spectrum is appropriate for our empiric sepsis protocol in high-risk patients, and we have noted a manageable side effect profile.” – Clinical Pharmacist, Major Metropolitan Hospital.
• “We utilized Doxt SL for a case of multidrug-resistant Acinetobacter ventilator-associated pneumonia. The patient had failed previous regimens. We observed a significant clinical improvement and eventual culture clearance after initiating therapy. A powerful option for resistant Gram-negative infections.” – ICU Director.