Battle of the Bugs: Is Long-term Daily Use of Low-Dose Antibiotics Safe?

Most doctors will tell you that long-term daily low-dose use of antibiotics is not recommended. It can lead to the development of resistant strains of bacteria, an increasingly serious problem. But sometimes, the benefits can outweigh the risks.

Many of us have had problems with infected wounds or sores. Over my 50-year life as a T11 para (I’m now 70), I have had about 20 cellulitis infections — five in one year. In 2012 I got what seemed to be the mother of all cellulitis infections in my left lower leg. What started as a large blood blister turned into a larger, nasty, deep wound.

No matter what I did — take the usual meds or frequent the wound care clinic, the wound did not show signs of healing. I took my cephalexin, went to a vascular surgeon, wore a wound vac, had a stent implanted and an artificial femoral artery graft. The wound finally began healing with improved circulation, but the infection had gotten into my bone. The heel of my left foot literally rotted away. Amputation was the best choice at that point.

A year later the same thing happened to my right leg, but this time the femoral graft prevented amputation.

At this point Dr. Bruce Ruben, who had been acting as a medical advisor from his home state of Michigan, came to see me while vacationing not far from where I live in Oregon. In my home he examined my still healing wound and took a complete medical history, pre- and post-injury. He then wrote up a plan of treatment, which included using Unna boot compression wraps (changed twice weekly), compression therapy when the wound healed, a possible venous ablation procedure to correct venous insufficiency from my calf “muscle pumps” not working properly, zero external pressure, and a daily dose of amoxicillin as a long-term prophylactic to lower the risk of further infections.

Dr. Ruben prescribed my prophylactic daily dose of amoxicillin only after a thorough evaluation. He treated me — not just my wound — my whole body, my lifestyle, my history, and he did so carefully and with complete understanding of all medical options.

So far, after two years of taking 250 mg. of amoxicillin twice a day every day, I have had no skin problems, no infections. And as a possible beneficial side effect, I have not had a single UTI in that same time period, the first and only time this has ever happened. But Ruben would be the first to say that taking an antibiotic daily is not the sole reason for my infection-free status.

In my case, restored arterial blood supply is critical. Since I can’t deal with compression stockings, compression therapy with daily Ace bandage wraps is the key to preventing edema. Treating athlete’s foot to prevent skin cracks between toes, etc., is also important. Using lotion or Vaseline ointment on my legs to prevent dry skin is another preventative measure. And of course, avoiding pressure is a must.

But the last step in tilting the odds in my favor was the daily use of a proven, safe antibiotic, not as a “cure,” but to reduce the numbers of strep and staph germs on my body — the most common bacterial invaders in cases of cellulitis.

“Your own body is the key to this,” Ruben told me. “There are 11 trillion perfect copies of white cells manufactured from your bone marrow each day. They are the first defense infantry that protects you from invaders. So as long as staph and strep stay on your skin, and they do cover you, they usually don’t bother you. But when you cut yourself

[or have a crack or wound on your skin], those 11 trillion white blood cells circulate through your blood and target your skin where the breakthrough occurs. Within seconds they have eaten up the bacterial invaders and your wound is left to heal itself.”

Once my body’s problems — poor circulation, edema, dry skin, unnoticed pressure — had been corrected, healing followed. “Antibiotics are not an answer to disease,” says Ruben. “They are an adjunct to your natural immune system for treatment of disease.”

More Cellulitis Stories
Cellulitis can strike anywhere, but most often it is wherever circulation is compromised. NEW MOBILITY contributor Allen Rucker was struck by transverse myelitis in late 1996, effectively becoming a lower thoracic para overnight. Not long after that he developed sores on his outer ankles. “A number of these got infected and turned into cellulitis,” he says. “I would be hit by a fever and get very sick, 103 degrees or so, and have to go to the ER. My foot and lower leg would get red and sometimes a red line would start creeping up my leg.” Usually a vancomycin drip did the trick, but the problem would return from time to time. “Sometimes it seems I didn’t even have to have a visible break in the skin.”

Another problematic area was Rucker’s trochanter — the bony prominence where the thigh and hip attach. About two years ago he had especially bad cellulitis in that area and had to be hospitalized for several days. Doctors tried various meds, but nothing worked. “The infectious disease doctor told me they could not ID the invading bacteria,” he says. “That was a scary moment. Finally they found the right ‘cocktail’ mix, and following that they did a tricky skin flap operation. That’s when my doctor decided I should take 250 mg. of Keflex [cephalexin] twice daily. It has been about two years and I haven’t had any recurrence of cellulitis since then.”

Rabbi Herschel Finman, 57, also sees Ruben. “I have neuropathy, no sensation in my feet, and I get athlete’s foot but don’t know it.” Finman has had three cellulitis infections in the last few years. “About one a year,” he says. “The first time I got cellulitis I ran a 104-degree fever and got very sick. The redness started in my foot and traveled above my ankles to about mid-calf.” Since Ruben offers IV infusion therapy seven days per week in his office, Finman went there instead of the ER. “I went in twice a day for a week. The fever broke right away, and I went back to work.”

But cellulitis came around a second time and a third time. In all three cases, he went in for infusion therapy with penicillin, and in all cases the infection responded right away. Still, he and Ruben began discussing the possibility of low-dose prophylaxis for prevention. Didn’t the possibility of developing a disease-resistant bug from taking a daily antibiotic worry him?

“No, not at all,” he says. “I read studies and discussed this at length with Dr. Ruben. I have full confidence in him and in the prophylactic treatment, and I don’t expect infection to return at all.” He takes 250 mg. of penicillin twice a day to keep the numbers of harmful streptococci bacteria low and has been infection-free for three years now.

What About UTIs?
Taking low-dose antibiotics for urinary tract infections is more complicated than with cellulitis. For those of us who have spinal cord injuries, a UTI can be difficult to self-diagnose, unlike cellulitis, which results in visible redness, swelling, and often a high fever. Low-grade UTIs can be mistaken for a sore back, fatigue, or other problems. Because of this, many of us with SCI tend to call the doctor and ask for a prescription at the first sign of discomfort. Most doctors, and just about all clinical studies, warn against this approach.

“The two main rules,” says Ruben, “are only take antibiotics when you are really sick, and if you’re not sick, don’t go to the doctor.”

A bacterial build-up is not the same as infection. People with SCI and neurogenic bladder tend to have large numbers of multiple types of bacteria adhering to the walls of the bladder. This can result in cloudy, smelly urine and feeling “off,” but absent fever or pain, it is most likely a colonization, not a true infection. Usually drinking water and cathing more frequently can clear out an asymptomatic bacterial buildup. Symptoms of true infection are fever, possibly chills, back pain, spasms, and autonomic dysreflexia.

Eric Stampfli, 57, is a T11-12 para, 40 years post-injury. He went through bladder training in rehab at Santa Clara Valley Medical Center, where he began wearing an external condom catheter and a legbag. Due to uncontrollable leakage at unpredictable times, he still uses this system.

In the early years following his injury, like most paras, when he noticed any symptoms he would immediately be put on antibiotics. “Now that I have decades of experience,” he says, “I think maybe I didn’t need them at all. Most of my symptoms could be explained by my being dehydrated. Nine out of 10 times, that is the problem.”

At that time, Septra or Bactrim —sulfamethoxazole/trimethoprim — was the drug of choice for SCI and UTIs. Stampfli took it a number of times and it worked well, but then something strange happened. “I started getting a weird reaction on my hands, splitting and cracking skin, losing skin. Turns out it was Stevens-Johnson syndrome,” he says. Whenever he went off Septra, the reaction would stop, and when he went back on it, it would start again.

About this time he started taking nitrofurantoin — Macrodantin or Macrobid — for low-dose daily prophylactic use, 100 mg. per day. “I got the original prescription from an older doctor, but all other doctors have gone along with it,” he says. “Infections have definitely gone down. I may get one occasionally, but not severe. The incidence of infections is way lower than it used to be.” He does add, however, that this may be partially explainable by his having learned how to take better care of himself as he has gotten older.

A 2014 study on nitrofurantoin claims that it is a good choice for low-dose daily use, partly because bacterial resistance to it has remained “virtually unchanged since its discovery.” Side effects, compared to other antibiotics used to treat UTIs, are minimal. However, the possibility of pulmonary problems such as shortness of breath in a small number of users indicates the need for close monitoring. “When I first went into Kaiser, a doctor insisted on lung studies,” says Stampfli. “But I haven’t had any problems with taking it.” He says he has been taking it for 30 years and doesn’t have any plans to stop taking it.

Every Body’s Different
John Smith, Jr. had a completely different experience with Macrodantin. Apparently he was one of that “small number” who can have an adverse reaction. Smith, 59, a C5 quad, was taking a low dose of one pill daily, like Stampfli. “After four months, I developed a raging infection with a side effect of pulmonary edema, and the doctor wanted to up the dosage, but I thought Macrodantin could be the problem,” says Smith. “He ignored me and increased the dosage, and the swelling in my lungs got worse and it was harder to breathe. I stopped taking it and the doctor threw a fit. But the next day the swelling went down. I am actually allergic to Macrodantin.”

Smith now manages his bladder by trying to avoid antibiotics altogether. “I still take Mandelamine (methenamine) and vitamin C,” he says. Methenamine is an antiseptic for the bladder but not an antibiotic, and should not be taken with Ciprofloxacin or Bactrim without first checking with a doctor. Smith takes 500 mg. daily of Mandelamine with plenty of water. “I just know that on me it works really well.”

Joan Anglin is a 76-year-old C4 quad, injured 25 years ago, who lives an active lifestyle, spending as much time as possible in her greenhouse, where she produces thousands of seedlings. She has been taking a daily low dose of Bactrim for almost six years with no problems — unlike Stampfli’s experience. “This last February was my first UTI in almost three years,” she says. “Bactrim seems to be helpful. When I went off of it for a year, it got much worse.” She says she doesn’t understand how it works, but it does. “My doctor says using Bactrim like this doesn’t make sense, but he does it with one other quad, and it’s working with both of us, so he wants to keep using it.”

Clearly, no doctor has a crystal ball that produces a one-size-fits-all treatment for everyone.

What Can We Conclude?
Jerome Stenehjem, M.D., physiatrist and medical director of SHARP Alison deRose Rehabilitation Center, thinks long-term antibiotic therapy for UTI prevention in SCI is where the art of medicine intersects with science. “In theory,” he says, “long term use of a drug like nitrofurantoin, or any other antibiotic, to prevent UTIs should not work due to development of resistant organisms. However, empirically, and inexplicably, it often does work.” Where recurrent UTIs are a vexing problem, he thinks it may be “worth a try” for the patient and the treating doctor, with close monitoring.

He has also learned another prevention technique that he is eager to share. “I have had great success with bladder irrigation. Once a day, after draining the bladder, a 30 ml. solution of gentamycin is infused and left in the bladder. This has the advantage of having no systemic effect but good efficacy in the bladder.”

In interviewing medical experts and numerous people who have experience with daily low-dose prophylactic use of antibiotics, some of whom are not included in this article, two strong themes emerged. First, whether treating cellulitis or UTIs, we all have unique reactions to antibiotics — what works for one person does not necessarily work for another. Second, antibiotics can be harmful as well as beneficial.

The lesson is clear: Be certain to find a doctor who knows your medical history well, is familiar with your disability, and keeps up with the latest studies on antibiotic use. The decision to start a prophylactic regimen of daily low-dose antibiotics should not be made without carefully weighing risks versus benefits for your unique situation. And close monitoring of potential side effects is also a given.

Studies of Interest
Cellulitis:  “Antimicrobial Prophylaxis in Adults,” Mayo Clinic Proceedings, July 2011; www.ncbi.nlm.nih.gov/pmc/articles/PMC3127564/.

Nitrofurantoin:  “Role of Old Antibiotics in the Era of Antibiotic Resistance,” February 2014; www.mdpi.com/journal/antibiotics.

Urinary Tract Infections: “Prevention of Urinary Tract Infection for Patients with Neurogenic Bladder,” University of Michigan, Current Bladder Dysfunction Reports, December 2014; link.springer.com/article/10.1007%2Fs11884-014-0257-4#page-1

• “Urinary Tract Infections in Spinal Cord Injury,” Harvard Medical School, 2014; emedicine.medscape.com/article/2040171-overview

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