Trimethoprim-Sulfamethoxazole (Bactrim/TMS)

Trimethoprim-sulfamethoxazole, commonly abbreviated as TMS and widely known by brand names including Bactrim, Septra, and Sulfatrim, stands as one of the most frequently prescribed antibiotics in rabbit medicine due to its broad-spectrum efficacy and excellent safety profile in this species. This potentiated sulfonamide combination represents a cornerstone medication for treating bacterial infections in rabbits, offering reliable coverage against many common pathogens without the dangerous gastrointestinal effects associated with penicillin-type antibiotics. The medication combines two antimicrobial agents in a fixed ratio that provides synergistic bactericidal activity against susceptible organisms, making it more effective than either component used alone.

The mechanism of action of trimethoprim-sulfamethoxazole involves sequential blockade of the bacterial folic acid synthesis pathway at two distinct enzymatic steps. Sulfamethoxazole competitively inhibits dihydropteroate synthase, the enzyme that incorporates para-aminobenzoic acid into dihydrofolic acid, while trimethoprim inhibits dihydrofolate reductase, which converts dihydrofolic acid to the active tetrahydrofolic acid form. This dual blockade creates a potentiated effect that produces bactericidal activity at therapeutic concentrations, whereas either drug alone would only slow bacterial growth without killing the organisms. The combination also reduces the likelihood of bacterial resistance developing compared to monotherapy. Mammalian cells remain unaffected because they obtain folic acid from dietary sources rather than manufacturing it internally.

Trimethoprim-sulfamethoxazole is available in multiple formulations that can be adapted for rabbit use, including oral suspension, tablets of various strengths, and injectable solutions for severe infections. The liquid suspension form is particularly useful in rabbit medicine as it allows precise dose measurement for small patients and can be administered via oral syringe. While the medication is approved for human use, it is commonly used off-label in veterinary medicine with well-established dosing protocols for rabbits specifically. Veterinary pharmacies can compound the medication into appropriate concentrations when commercial human formulations are not ideal for rabbit dosing. Administration typically occurs once or twice daily depending on the clinical situation.

Despite its favorable safety profile, trimethoprim-sulfamethoxazole treatment in rabbits requires appropriate veterinary oversight to ensure optimal outcomes. A rabbit-savvy veterinarian should evaluate the patient, confirm the diagnosis, select the appropriate antibiotic, and determine proper dosing based on body weight and condition severity. Accurate weighing in grams provides the foundation for precise dosing in these small patients. While TMS ranks among the safest antibiotic options for rabbits, monitoring throughout treatment remains important to detect any adverse effects early and confirm therapeutic response to the medication.

Trimethoprim-sulfamethoxazole serves as a first-line antibiotic choice for numerous bacterial infections in rabbits, with respiratory tract disease representing one of its most common applications. Upper respiratory infections characterized by nasal discharge, sneezing, conjunctivitis, and facial swelling frequently respond well to this medication. Pasteurella multocida, the bacterium responsible for the syndrome commonly called "snuffles" and numerous other infections in rabbits, typically demonstrates good susceptibility to TMS. Lower respiratory infections involving bronchitis or pneumonia also benefit from this medication when Pasteurella or other susceptible organisms are implicated. Early treatment can help prevent progression from mild upper respiratory signs to life-threatening pneumonia.

Urinary tract infections represent another primary indication for trimethoprim-sulfamethoxazole in rabbits, as the medication achieves excellent urinary concentrations that provide therapeutic activity against common uropathogens. Clinical presentations suggesting urinary infection include frequent urination attempts, straining, vocalization during urination, blood-tinged urine, thick or sludgy urine, urine scalding of the perineum, and altered litter box habits. Rabbits predisposed to urinary issues due to diet, hydration status, or underlying conditions such as bladder sludge accumulation may develop recurrent infections benefiting from antibiotic therapy alongside management of contributing factors.

Skin and soft tissue infections in rabbits, including abscesses, wound infections, pododermatitis with secondary bacterial involvement, and bite wounds, often warrant TMS treatment. While rabbit abscesses characteristically contain thick, caseous pus that limits antibiotic penetration and often requires surgical management, concurrent systemic antibiotic therapy addresses surrounding tissue infection and helps prevent systemic spread. The medication's good tissue penetration makes it useful for cellulitis, surgical site infections, and traumatic wounds with bacterial contamination. Treatment duration for soft tissue infections varies based on severity and may be prolonged for chronic or recurrent conditions.

Coccidiosis, caused by Eimeria protozoan parasites affecting the intestinal tract or liver, responds to the sulfonamide component of TMS. Young rabbits between weaning and approximately four months of age are particularly susceptible to this parasitic disease, which can cause diarrhea, weight loss, poor growth, and potentially death in severe cases. While other coccidiostatic medications exist, TMS provides the added benefit of antibacterial coverage for any secondary bacterial infection complicating the parasitic disease.

Veterinarians select trimethoprim-sulfamethoxazole over alternative safe antibiotics based on factors including suspected or confirmed pathogen susceptibility, infection site, prior treatment history, patient factors, and practical considerations. The medication's availability in liquid form facilitates accurate dosing in rabbits of various sizes. For chronic or recurrent infections, culture and sensitivity testing may guide antibiotic selection to confirm susceptibility. The relatively low cost and wide availability of TMS compared to some veterinary-specific antibiotics makes it an accessible option for many rabbit owners.

Proper dosing of trimethoprim-sulfamethoxazole in rabbits requires determination by a qualified rabbit-savvy veterinarian, as dosing protocols for rabbits differ from those used in other species and depend on the specific condition being treated. The veterinarian calculates appropriate doses using current rabbit medicine references, clinical experience, and individual patient factors including body weight, infection severity, and overall health status. Rabbits should be weighed accurately in grams to minimize dosing calculation errors that could result in inadequate therapy or increased toxicity risk. Regular weight monitoring throughout treatment helps track response and detect potential complications.

Typical administration protocols involve oral dosing once or twice daily, with the specific interval determined by the clinical situation and formulation used. Twice-daily dosing maintains more consistent blood levels and may be preferred for serious or systemic infections, while once-daily dosing offers convenience advantages for milder conditions or long-term maintenance therapy. The standard ratio of trimethoprim to sulfamethoxazole in commercial preparations is 1:5, and dosing calculations account for both components. Injectable forms exist for situations where oral administration is not feasible, though parenteral use is less common in rabbit medicine than oral therapy.

Treatment duration varies considerably depending on the type and severity of infection. Uncomplicated urinary tract infections may respond to one to two weeks of therapy, while respiratory infections involving pasteurellosis often require extended treatment of three to four weeks or longer. Chronic or recurrent infections may need prolonged maintenance therapy, and some conditions such as established pasteurella infections may never be completely eradicated. The prescribing veterinarian will advise on anticipated treatment length and schedule follow-up evaluations to assess response. Premature discontinuation of antibiotics risks treatment failure and resistance development.

Oral administration to rabbits requires gentle handling techniques to minimize stress while ensuring medication delivery. The commercially available pediatric oral suspension can be administered directly via oral syringe, with the syringe tip positioned behind the front incisors at the side of the mouth. Giving small amounts slowly allows the rabbit to swallow without aspiration risk. Some rabbits accept medication mixed into favorite foods such as mashed banana, pureed papaya, baby food fruit purees without added sugar, or a small amount of Critical Care. Palatability varies between individual rabbits, and direct syringing may be more reliable for ensuring complete dose delivery in reluctant patients.

Missed doses should be administered as soon as discovered unless the next scheduled dose is approaching, in which case the missed dose should be skipped and regular timing resumed. Double doses should never be given to compensate for missed medication, as this increases adverse effect risk without therapeutic benefit. Contact the veterinarian for guidance if multiple consecutive doses are missed, as treatment extension may be needed. Maintaining consistent dosing times helps sustain therapeutic blood levels throughout treatment.

Completion of the entire prescribed course remains essential even when clinical improvement occurs before all medication is finished. Stopping antibiotic therapy early allows surviving bacteria to repopulate and potentially develop resistance, leading to recurrent infection that may be more difficult to treat. Follow-up veterinary visits may be recommended to confirm treatment success, particularly for serious infections, chronic conditions, or valuable breeding animals where ensuring infection clearance is important.

Trimethoprim-sulfamethoxazole demonstrates a favorable safety profile in rabbit patients when administered at appropriate doses under proper veterinary supervision. The medication's mechanism targeting bacterial folic acid synthesis rather than mammalian pathways contributes to its tolerability in this species. However, potential side effects exist with any medication, and owner awareness enables early recognition and appropriate response. The most critical monitoring parameters for rabbits receiving any medication involve appetite and fecal production, as these indicators reflect overall health and gastrointestinal function in this hindgut-fermenting species where digestive disruption can rapidly become life-threatening.

Common mild side effects occasionally observed during TMS treatment include temporary appetite reduction, particularly during the initial days of therapy as the rabbit adjusts. Some patients may produce slightly softer fecal pellets than their normal baseline during treatment, though this typically does not progress to problematic diarrhea. Mild decreased activity during early treatment is occasionally noted but usually improves as the underlying infection responds to therapy and the rabbit begins feeling better. Gastrointestinal upset manifesting as temporary nausea or reduced food interest occurs in some individuals but is generally self-limiting and does not require treatment modification.

Moderate side effects warranting veterinary consultation include significant or prolonged appetite reduction lasting beyond one to two days of treatment, notable changes in fecal pellet quantity or quality beyond mild softening, or signs suggesting dehydration. Crystalluria, the formation of sulfonamide crystals in urine, can occur particularly when hydration is inadequate or with prolonged high-dose therapy. Signs potentially indicating urinary tract irritation from crystalluria include increased urination frequency, straining, small urine volumes, or apparent discomfort during urination. Maintaining excellent hydration throughout treatment by ensuring unlimited fresh water access represents the primary preventive measure. Skin reactions including rash, itching, or hair loss are uncommon but possible allergic manifestations.

Serious side effects requiring immediate veterinary attention include signs of gastrointestinal stasis such as complete appetite loss persisting more than twelve hours, dramatic reduction or cessation of fecal pellet production, abdominal distension or bloating, teeth grinding indicating pain, or hunched posture suggesting discomfort. While TMS does not carry the fatal dysbiosis risk associated with penicillin-type antibiotics, any medication can potentially affect gastrointestinal function in susceptible individuals. Severe allergic reactions, though rare, constitute emergencies. Signs suggesting bone marrow effects, including unusual bleeding or bruising, pale mucous membranes, or profound lethargy possibly indicating anemia, require prompt evaluation.

Rare side effects reported with trimethoprim-sulfonamide combinations include blood dyscrasias such as anemia, thrombocytopenia, or leukopenia, particularly with extended treatment duration. Hepatic effects are uncommon at standard doses but possible. Any unusual symptoms developing during treatment should prompt veterinary contact to determine whether they represent medication effects, progression of underlying disease, or coincidental unrelated issues.

Trimethoprim-sulfamethoxazole should not be administered to rabbits with known hypersensitivity or documented allergic reactions to trimethoprim, sulfamethoxazole, other sulfonamides, or any inactive ingredient in the formulation being used. Cross-reactivity among different sulfonamide medications means that rabbits experiencing adverse reactions to any sulfa drug should generally avoid the entire medication class unless a rabbit-savvy veterinarian specifically determines the risk-benefit ratio favors treatment. Previous allergic manifestations may have included skin eruptions, swelling, respiratory difficulty, or systemic reactions, and this medical history must be clearly communicated to any veterinarian prescribing medications for the rabbit.

Significant kidney disease represents a relative contraindication requiring careful veterinary evaluation before initiating trimethoprim-sulfamethoxazole therapy. Both drug components undergo renal excretion, and impaired kidney function can cause drug accumulation with increased toxicity potential. The sulfonamide component's potential for crystal formation in urine poses additional concern in patients with compromised renal function or concentrated urine production. Rabbits with diagnosed kidney disease, clinical signs suggestive of renal impairment such as polyuria and polydipsia with weight loss, or geriatric rabbits at elevated risk for age-related renal decline warrant thorough evaluation before treatment. Dose reduction, extended dosing intervals, or selection of alternative antibiotics may be appropriate depending on the degree of renal compromise.

Hepatic impairment also warrants caution when considering trimethoprim-sulfamethoxazole, as liver metabolism contributes to drug processing. Rabbits with known liver disease, evidence of hepatic dysfunction on blood chemistry, or clinical signs suggesting liver problems may require dosage adjustment or alternative medication selection. Severely debilitated rabbits may have compromised organ function even without specifically diagnosed disease, necessitating careful treatment planning and enhanced monitoring.

Pregnant and nursing does require thorough risk-benefit assessment before trimethoprim-sulfamethoxazole administration. Both medication components cross the placenta and enter milk, potentially exposing developing fetuses and nursing kits. Theoretical concerns include interference with folate-dependent processes in rapidly developing tissues and potential effects on kit intestinal flora establishment. While the medication has been used in pregnant and nursing rabbits when infection severity justified the risk, veterinary guidance is essential for determining appropriate timing, considering alternatives, or accepting calculated risks. Rabbits with active gastrointestinal stasis or severe dehydration should have these conditions stabilized before or concurrent with initiating antibiotic therapy, as adequate hydration is particularly important for safe sulfonamide excretion.

Complete disclosure of all medications, supplements, and dietary additives the rabbit receives is essential before starting trimethoprim-sulfamethoxazole treatment. Drug interactions can significantly affect medication efficacy, increase toxicity risk, or complicate clinical monitoring. This disclosure should include prescription medications, over-the-counter products, herbal remedies, dietary supplements, and any additives commonly used by rabbit owners. Products such as papaya enzyme tablets, probiotic supplements, vitamin preparations, and herbal products all warrant mention during veterinary consultation to enable proper interaction assessment.

Potentially significant interactions may occur when trimethoprim-sulfamethoxazole is combined with other medications affecting renal function or sharing renal excretion pathways. Concurrent administration of potentially nephrotoxic agents should be avoided when possible, as combined effects could increase kidney damage risk. Medications altering urine pH may affect sulfonamide solubility and crystallization potential in the urinary tract. Trimethoprim can increase levels of certain medications by inhibiting their metabolism, and concurrent use of other folate antagonists such as methotrexate should be avoided due to additive effects on folate pathways. Warfarin and similar anticoagulants may have enhanced effects when combined with TMS.

Combining trimethoprim-sulfamethoxazole with other antibiotics requires expert veterinary evaluation to ensure the combination is appropriate rather than antagonistic. While TMS provides broad coverage for many infections, certain complex situations might theoretically benefit from combination therapy under specific circumstances. However, combining antibiotics without veterinary direction risks both reduced efficacy and increased adverse effects. Most critically, trimethoprim-sulfamethoxazole must never be combined with antibiotics dangerous to rabbits, including amoxicillin, ampicillin, clindamycin, lincomycin, erythromycin, oral penicillins, and most cephalosporins. These medications cause fatal gastrointestinal dysbiosis in rabbits regardless of what other safe medications might be co-administered.

Probiotic supplementation is commonly recommended for rabbits receiving any antimicrobial therapy to help maintain beneficial intestinal flora. However, probiotics and TMS should be administered at least two hours apart to avoid potential interference with probiotic organism viability. Maintaining the high-fiber diet essential for rabbit gastrointestinal health throughout antibiotic treatment supports the beneficial bacteria that maintain healthy gut function. Unlimited hay access should continue, and any changes in eating patterns, fecal output quality or quantity, or cecotrope consumption should be reported to the veterinarian promptly, as these may indicate gastrointestinal effects requiring attention.

Trimethoprim-sulfamethoxazole treatment should always occur under the supervision of a veterinarian knowledgeable about rabbit medicine, as appropriate diagnosis, medication selection, dosing, and monitoring are essential for safe and effective therapy. Rabbit medicine represents a specialty area, and not all veterinarians have extensive experience with this species. Identifying a rabbit-savvy practitioner provides the foundation for optimal care. Accurate body weight measurement in grams rather than pounds minimizes dosing calculation errors that could result in therapeutic failure or increased toxicity in these small patients. Weight should be determined at treatment initiation and monitored throughout therapy, as changes may reflect treatment response or emerging complications.

Breed-specific considerations for TMS relate primarily to size variations affecting dosing precision. Dwarf breeds including Netherland Dwarfs, Holland Lops, Mini Rex, Polish, Jersey Woolys, and Dwarf Hotots require particularly careful attention to dose calculations because their small adult weights of two to four pounds mean even minor mathematical errors translate to significant percentage variations in actual dose received. Compounded liquid formulations allowing precise measurement of small volumes are often preferred for these diminutive patients. Giant breeds such as Flemish Giants, Continental Giants, and British Giants require higher absolute doses based on their substantial body weights but do not have known increased sensitivity to the medication. Size-appropriate formulations and concentrations help ensure accurate dosing across the breed spectrum.

Environmental precautions during treatment include proper medication storage and handling, keeping the medication secured away from children and other household pets, and clear labeling of medicated preparations. In multi-pet households, care should be taken to ensure only the intended patient receives the medication. Some commercial TMS preparations contain flavorings that may be attractive to other animals, making secure storage particularly important. Handlers should wash hands after administering medication.

Monitoring during treatment should focus on key health indicators including appetite, water consumption, fecal pellet production and quality, cecotrope consumption, activity level, and overall demeanor. Appetite reduction lasting more than twelve hours warrants veterinary contact, as rabbits can develop life-threatening gastrointestinal stasis rapidly when food intake ceases. Fecal output should be observed for quantity and quality changes, watching for significant reductions or alterations suggesting gastrointestinal complications. Accumulation of uneaten cecotropes may indicate illness. Signs of the underlying infection should be monitored for improvement or deterioration.

Special populations requiring additional precautions include geriatric rabbits with potential age-related organ function decline, young rabbits with developing physiological systems, and immunocompromised individuals. Rabbits with concurrent chronic conditions such as E. cuniculi infection, dental disease, or metabolic disorders may need modified treatment approaches and enhanced monitoring. Post-surgical patients, pregnant does, and nursing mothers with dependent kits all warrant careful consideration of treatment timing and potential effects.

Proper storage of trimethoprim-sulfamethoxazole maintains medication potency and safety throughout the treatment course. Storage requirements vary by formulation, and label directions should be followed precisely. Tablets should be stored at room temperature in their original containers or appropriate pharmacy-provided packaging, protected from excessive heat, light, and moisture. Oral suspension formulations may require refrigeration after opening, depending on the specific product, and typically have limited stability after the bottle is first accessed. The suspension should be shaken thoroughly before each dose to ensure uniform drug distribution throughout the liquid. Injectable formulations have specific storage requirements that should be followed as directed.

Compounded medications prepared by veterinary or human pharmacies to provide appropriate concentrations for rabbit patients are commonly used and typically have shorter shelf lives than commercial products. Storage requirements for compounded preparations may differ from original commercial products and should be clarified with the dispensing pharmacy. The beyond-use date assigned by the compounding pharmacy should be noted and respected, as potency cannot be guaranteed beyond this date. Any changes in medication appearance, including color alterations, cloudiness in previously clear liquids, precipitation, unusual odor, or visible degradation, should prompt disposal rather than continued use.

Preparing and administering oral medication requires attention to hygiene and dosing accuracy. Oral dosing syringes should be rinsed between uses to prevent bacterial growth and medication buildup. Liquid medication should be measured carefully using provided droppers or syringe markings to ensure accurate dosing. Tablets requiring division should be split carefully using appropriate tools when available. Contact the veterinarian or pharmacy if dosing instructions are unclear or if the provided formulation makes accurate dosing difficult for the patient's size.

Safe disposal of unused trimethoprim-sulfamethoxazole should follow local pharmaceutical disposal regulations. Many communities offer medication take-back programs that accept both human and veterinary pharmaceuticals. Medications should not be flushed down toilets or drains unless specifically directed by label instructions, as this contributes to environmental contamination and potential antibiotic resistance development in environmental bacteria. Unused medication should be disposed of in ways preventing accidental ingestion by children, pets, or wildlife. Empty containers should be rendered unsuitable for reuse. Keeping all medications secured away from curious rabbits is important, as rabbits may chew through packaging materials if given access.

Trimethoprim-sulfamethoxazole can be administered safely across rabbit breeds when properly dosed according to individual body weight under appropriate veterinary supervision. No specific breed demonstrates inherent increased sensitivity or altered response to this medication. However, the substantial size variation among rabbit breeds creates important practical considerations for accurate dosing and appropriate treatment administration that warrant attention across all breed categories.

Dwarf breeds require particular attention to dosing precision due to their small adult body weights, typically ranging from approximately two to four pounds for breeds including Netherland Dwarfs, Holland Lops, Mini Rex, Polish, Jersey Woolys, and Dwarf Hotots. This diminutive size means that even small errors in dosing calculations or measurement translate to larger percentage variations in actual dose delivered, potentially affecting both treatment efficacy and safety margins. Compounded liquid formulations allowing precise measurement of small volumes are generally preferred for dwarf breed rabbits. Very young dwarf rabbits requiring treatment may be especially tiny, potentially weighing only ounces, necessitating careful veterinary guidance on appropriate dosing approaches. Despite their small size, dwarf breeds are fully susceptible to the infections that TMS treats and benefit equally from appropriate antibiotic therapy.

Giant breeds including Flemish Giants, Continental Giants, British Giants, and Giant Chinchillas may exceed fifteen pounds as adults, requiring appropriately larger absolute medication doses while maintaining correct mg/kg dosing. These larger patients can typically receive standard formulations without requiring the specialized concentration adjustments often necessary for smaller rabbits. Giant breeds may experience musculoskeletal conditions affecting mobility and handling but have no known differential sensitivity to TMS. French Lops and other large lop breeds fall between standard and giant size categories with corresponding intermediate dosing considerations.

Lop breeds across size categories share anatomical ear characteristics predisposing them to ear infections due to reduced air circulation within the ear canal. While TMS effectively treats systemic infections, ear infections often require concurrent topical therapy and potentially extended treatment courses. Rex breeds and their miniature variants have no specific TMS considerations beyond size-appropriate dosing for Mini Rex individuals. Angora, Jersey Wooly, and other wool breeds may present challenges for monitoring hydration status through visual assessment due to their dense coats but have no specific systemic medication considerations.

Age-related factors apply across all breeds regardless of size. Young rabbits may have developing organ systems affecting drug handling and are frequently the patients presenting with respiratory infections or coccidiosis requiring treatment. Geriatric rabbits may have age-related decline in kidney or liver function affecting drug metabolism and excretion. Pre-treatment health assessment is valuable in older patients to identify concerns that might affect treatment safety or require dose modification.

Several alternative antibiotics considered safe for rabbits may be substituted when trimethoprim-sulfamethoxazole is inappropriate or when different antimicrobial coverage is needed. Trimethoprim-sulfadiazine (Tribrissen) offers nearly identical coverage using a different sulfonamide partner combined with trimethoprim and may be selected based on formulation preference or availability. Sulfaquinoxaline provides sulfonamide coverage without trimethoprim potentiation and is commonly used specifically for coccidiosis treatment and prevention. These related sulfonamide options share mechanism similarities and comparable safety profiles in rabbits.

Enrofloxacin (Baytril) represents a different antibiotic class, the fluoroquinolones, providing excellent coverage against many gram-negative bacteria and some gram-positive organisms commonly affecting rabbits. This medication is frequently prescribed for respiratory infections, urinary tract infections, and other bacterial conditions with an established safety record in the species. Marbofloxacin and ciprofloxacin offer alternative fluoroquinolone options. Chloramphenicol provides broad-spectrum coverage with excellent tissue penetration, though handler precautions are necessary due to rare idiosyncratic reactions in humans. Metronidazole is effective against anaerobic bacteria and certain protozoal organisms. Azithromycin may be used for specific respiratory infections including some mycoplasma species. These safe alternatives expand treatment options when TMS is not suitable.

Critically, certain antibiotics must never be used in rabbits regardless of the clinical situation due to their potential to cause fatal gastrointestinal dysbiosis. Amoxicillin, ampicillin, clindamycin, lincomycin, erythromycin, oral penicillins, and most cephalosporins destroy the beneficial intestinal bacteria essential for normal rabbit digestive function. The resulting overgrowth of toxin-producing bacteria can cause rapid deterioration and death within hours to days. These dangerous antibiotics should never be administered to rabbits under any circumstances, and all rabbit owners should understand this critical safety information to prevent well-intentioned but potentially fatal treatment errors. Injectable penicillin G may be used under specific circumstances by veterinarians but oral penicillins remain absolutely contraindicated.

Supportive therapies complement antibiotic treatment in rabbit patients. Probiotic supplementation helps maintain beneficial gut flora during any antimicrobial therapy and should be given at least two hours apart from antibiotic doses. Maintaining high-fiber hay intake throughout treatment supports gastrointestinal health. Assisted feeding with products like Critical Care may be necessary for patients with reduced appetite. Adequate hydration through unlimited fresh water access supports drug excretion and overall recovery. Any medication changes should only occur under veterinary direction to ensure continued safety and appropriate infection coverage.