Does Bactrim Treat Lyme Disease? What the Research Shows
Bactrim is not a standard first-line Lyme treatment
Laboratory studies suggest activity against stationary-phase B. burgdorferi enriched in persister cells
Clinical decisions still require caution and further research
Does Bactrim treat Lyme disease? Bactrim (trimethoprim-sulfamethoxazole) is not considered a standard first-line treatment for Lyme disease. However, laboratory studies suggest that Bactrim, dapsone, and certain antibiotic combinations have activity against stationary-phase Borrelia burgdorferi enriched in persister cells. These findings come primarily from laboratory and animal studies rather than clinical trials in humans.
Although these studies are encouraging, they should be interpreted cautiously. Laboratory and animal studies can identify promising drug combinations, but they do not prove that Bactrim- or dapsone-based regimens are effective or safe for routine treatment of Lyme disease in patients.
The authors identified, from an FDA drug library and an NCI compound library, three sulfa drugs and trimethoprim for study. “Dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested.” [1]
Combinations of antibiotics were more effective in eradicating B. burgdorferi in stationary-phase cell culture.
- Sulfa drugs combined with other antibiotics were more active than their respective single drugs.
- Four-drug combinations were more active than three-drug combinations.
- Four-drug combinations (dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin) showed the greatest activity among the sulfa-drug combinations evaluated.
- Even these four-drug combinations remained less active than daptomycin + cefuroxime + doxycycline, the positive-control regimen that completely eradicated stationary-phase B. burgdorferi in this laboratory model.
Why researchers study persister cells
Borrelia burgdorferi behaves differently depending on its growth phase. Laboratory studies have shown that stationary-phase organisms are more tolerant of antibiotics than actively growing spirochetes. For this reason, investigators frequently evaluate new drug combinations against stationary-phase cultures enriched in persister cells.
Persister-cell research does not mean that every patient with persistent symptoms has ongoing infection. Post-treatment Lyme disease symptoms may reflect several mechanisms, including immune activation, inflammation, tissue injury, coinfections, persistent organisms, or a combination of these factors. The relative contribution of each remains an area of active investigation.
What is Bactrim?
Bactrim and Septra are brand names for trimethoprim-sulfamethoxazole. Trimethoprim is not a sulfa drug, but it is commonly combined with the sulfa drug sulfamethoxazole. Together they are widely prescribed for a variety of bacterial infections unrelated to Lyme disease.
In the Feng study, sulfamethoxazole was the least active of the sulfa drugs tested against stationary-phase B. burgdorferi. Trimethoprim demonstrated activity similar to dapsone and sulfachlorpyridazine, although it did not demonstrate the same type of synergy with sulfa drugs observed in some other bacterial infections.
Why is Bactrim discussed in an article about Lyme disease?
Although Bactrim is not a standard treatment for Lyme disease, it has been used for certain Bartonella infections. Bartonella henselae, the bacterium that causes cat scratch disease, has been treated with trimethoprim-sulfamethoxazole in selected clinical situations. Bactrim has been used as one of several treatment options for selected Bartonella infections, including some cases of cat scratch disease, but this should not be interpreted as evidence that it is an established treatment for Lyme disease. [6]
Because Lyme disease and Bartonella coinfection can occur in some patients with tick-borne illness, clinicians may consider Bactrim in selected situations when Bartonella infection is suspected. However, evidence supporting its use for Lyme disease itself remains much more limited and comes primarily from laboratory and preclinical studies.
Dapsone and other drugs studied
Because dapsone was one of the most active drugs identified in the original laboratory study, it became the focus of additional preclinical research.
Dapsone, trimethoprim, and sulfamethoxazole are medications approved for other clinical indications. Dapsone is commonly used with rifampicin and clofazimine to treat leprosy and may cause hemolysis, methemoglobinemia, hepatitis, cholestatic jaundice, and skin rashes. Sulfachlorpyridazine is not currently used clinically.
Because dapsone can cause hemolysis and methemoglobinemia, patients are typically screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency before treatment and monitored during therapy.
Daptomycin is approved for serious skin and bloodstream infections, including Staphylococcus aureus bacteremia and right-sided endocarditis. It is marketed in the United States as Cubicin. Potential adverse effects include blood pressure changes, edema, insomnia, diarrhea, abdominal pain, eosinophilia, dyspnea, injection-site reactions, fever, and hypersensitivity. Rare cases of eosinophilic pneumonia have been reported, and myopathy or rhabdomyolysis may occur, particularly in patients taking statins.
What has been learned since the 2017 study?
The authors of the 2017 study emphasized the need for additional laboratory and animal research. Since then, investigators have extended combination-antibiotic research into a mouse model of persistent Borrelia burgdorferi infection.
In a 2023 mouse study, none of the antibiotic monotherapies eradicated detectable infection in the mouse model. However, several dual- and triple-drug combinations eradicated detectable infection, including doxycycline + ceftriaxone, dapsone + rifampicin, dapsone + clofazimine, doxycycline + cefotaxime, and dapsone + rifampicin + clofazimine. The investigators concluded that combination therapy deserves additional preclinical evaluation for Lyme disease.
These mouse studies provide stronger preclinical evidence than laboratory studies alone. Nevertheless, they do not establish that these regimens are effective or safe in patients with Lyme disease or post-treatment Lyme disease symptoms. Carefully designed human clinical trials remain necessary.
Why laboratory findings must be interpreted carefully
Laboratory and animal studies are valuable for identifying promising treatment strategies, but they cannot fully reproduce the complexity of infection in humans. Drug metabolism, tissue penetration, immune responses, microbial burden, host-pathogen interactions, and coinfections all influence clinical outcomes.
For that reason, activity against stationary-phase B. burgdorferi should not be interpreted as proof that a medication will be effective in patients. These studies are best viewed as hypothesis-generating research that guides future animal studies and ultimately clinical trials.
In my practice, treatment decisions are individualized based on each patient’s clinical presentation, response to therapy, and possible coinfections rather than laboratory studies alone. Laboratory findings provide valuable scientific direction, but they do not replace clinical judgment.
Frequently Asked Questions
Does Bactrim treat Lyme disease?
Bactrim is not considered a standard first-line treatment for Lyme disease. Laboratory studies suggest that trimethoprim and sulfa-drug combinations have activity against stationary-phase B. burgdorferi, but clinical evidence remains limited.
Is Bactrim better than doxycycline for Lyme disease?
No. Doxycycline remains one of the standard first-line antibiotics for early Lyme disease. Although Bactrim has shown activity in laboratory studies, these findings do not demonstrate superiority over doxycycline in patients.
Why would Bactrim be considered in a Lyme disease patient?
Some physicians may prescribe Bactrim when treating selected coinfections or other bacterial illnesses occurring in patients with Lyme disease. Its role as a treatment for Lyme disease itself remains uncertain.
Can Bactrim and azithromycin be taken together?
Bactrim and azithromycin can sometimes be prescribed together for selected bacterial infections. Whether this combination is appropriate depends on the patient’s diagnosis, medical history, and other medications and should be determined by the treating clinician.
What is the difference between dapsone and Bactrim?
Dapsone is a sulfone antibiotic, whereas Bactrim combines trimethoprim with the sulfa drug sulfamethoxazole. Although both have been investigated in laboratory studies of Lyme disease persister cells, they are different medications with distinct safety profiles and monitoring requirements.
Clinical Takeaway
Bactrim is not a standard first-line treatment for Lyme disease. However, laboratory studies have shown that Bactrim, dapsone, and certain antibiotic combinations have activity against stationary-phase Borrelia burgdorferi enriched in persister cells.
Subsequent animal studies have strengthened the biologic rationale for combination therapy, but these findings have not yet established that these regimens are effective or safe for routine treatment of patients with Lyme disease or post-treatment Lyme disease symptoms.
Current evidence supports continued research into combination therapy. Until human clinical trials are available, treatment decisions should continue to be individualized based on the patient’s clinical presentation, available evidence, and careful physician judgment.
Related Articles
Learn more about Lyme disease diagnosis, treatment, and persistent symptoms:
Lyme disease treatment
Why Lyme symptoms may persist after treatment
Lyme disease misdiagnosis
Recovery after Lyme disease
References
- Feng J, Zhang S, Shi W, Zhang Y. Activity of sulfa drugs and their combinations against stationary phase Borrelia burgdorferi in vitro. Antibiotics (Basel). 2017;6(1):10.
- Alruwaili Y, Jacobs MB, Hasenkampf NR, Tardo AC, McDaniel CE, Embers ME. Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease. Front Microbiol. 2023;14:1293300.
- Caskey JR, Embers ME. Persister development by Borrelia burgdorferi populations in vitro. Antimicrob Agents Chemother. 2015;59(10):6288-6295.
- Feng J, Shi W, Zhang S, Zhang Y. Persister mechanisms in Borrelia burgdorferi: implications for improved intervention. Emerg Microbes Infect. 2015;4(8):e51.
- Ghallab A. In vitro test systems and their limitations. EXCLI J. 2013;12:1024-1026.
- Florin TA, Zaoutis TE, Zaoutis LB. Beyond cat scratch disease: widening spectrum of Bartonella henselae infection. Pediatrics. 2008;121(5):e1413-e1425.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
Dr. Cameron, my daughter has many symptons of Lyme. She tested and mycoplasma was the only one that showed up from the Lyme test. . She has voice problems, swallowing problems, hair loss, sensory issues like smell is very strong to her, neurological issues make walking difficult, pain, numbness, brain fog, and so on. She never remembers being bitten by a tick. She has tried oral antibiotics but can never stay on them very long. Now she is weaker and feels like her digestive system is slowly shutting down,; swallowing is difficult. Is there anything she could do to build up her immune system before tackling antibiotics again? How difficult is it to do immunoglobulin IVs?
I am sorry to hear your daughter remains ill. It is hard to judge if a mycoplasma is the cause of an illness. It can be difficult to tolerate any treatment. IV antibiotics can also affect the stomach even with probiotics. There may be regimen(s) available if your reach out to your doctor. The alternative medicine field and IVIG have been proposed but it is difficult to evaluate without an one on one assessment. You may also need to make sure you do not have another illness.
I carried both of my children while I had Lyme disease. At the time didn’t know that I had it, but I’m always worried that I’ve passed it on to one or both of them. Every time they complain of any kind of ache I’m worried. I know they have done tests on cadavers with MS, ALS, and I think it was dementia, but when the brain stem was tested they all came back with the Borrelia bacteria. My mother has MS. Do you think it’s possible that she passed this virus onto me? I have never had a tick bite to my knowledge. When my test finally came back positive, I asked my mother if she ever remembers me having a tick as a child. She didn’t. So either I was bitten as a child or I wasn’t bitten at all and it was passed to me. I mean that’s how I see it. What is your opinion?
You have raised questions that are yet to be resolved. It is difficult to study transmission given the extensive exposure in a lifetime.
Dr. Cameron, have any of your patients used the Daptomycin + cefuroxime + doxycycline combination referenced in the article reviewed here? What are the potential downsides/negative side effects in vivo?
I have followed their in vitro results. I have not seen results beyond their cultures. It is unclear if the in vivo results will be as good or if there are any additional side effects in vivo. I have been reluctant to add Daptomycin to the regimen until more information is available.
Is there any specific, combination of antibiotics to treat ALS Lyme? Any other supplements will help for antibiotics resistant patients?
ALS and Lyme disease share some similar characteristics. Any evaluation should also include a neurologist. Any treatment must be individualized.
I did 2 months of iv daptomycine, doxy and oral ceftin because the lyme dr I was seeing said john Hopkins found this to be the cure.
8 months later I’m not better. Was that a waste of time?
I have left that dr and just started seeing a new one who has me in rifampin with supplements because a lot of my symptoms point to bart even though my test was negative. I asked if it should be combined with another antibiotic and she said not at this time.
I was you patient when living in ny . What do you think?
Daptomycin was helpful in the test tube. It still needs more research to determine if it will help in people. It can be difficult to determine who will benefit from additional antibiotics.
Cameron, I am newly diagnosed with Lyme, Bartonella, Mycoplasma and B. Burg. My Lyme Dr. Prescribed me Minocycline, Flagyl, Vibratabs and Valtrex, I am very ery sensitive to alot of medications and honestly I am afraid to take all of these pills. I have started a herbal protocol but it seems as though I am sensitive to some of these as well. Do you have any suggestions?
I typically start slower in patients sensitive to medications. I am curious why you mentioned Minocin and Vibratabs. Vibratabs are brand name doxycycline. I would not prescribe both.
Back in 2016 I had best results with a doxycycline + azithromycin + cefuroxime combination.
I was bit by a black legged tick in the fall 2012 and a black legged tick nymph in 2013. I became ill the first time in three months after the first bite. Never did quite feel well until an extended course of doxycycline, then an extended course of azithromycin added to that, then an extended course of cefuroxime added, all in combination. Took that combination until I presented well.
I find each of the antibiotics you have taken by themselves or in combination helpful for my patients without the treatment proposed in the culture. I also find treatment for Babesia helpful.
Hello dr. Cameron, what do you think about the combination of azithromycin and cefuroxim at the same time for a 10 year old boy with chronic lyme? Thank you!
I have used the combination in a few cases. I still have to individualize treatment and evaluate for other causes