Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
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Post by ChronicLyme19 » Tue 6 Jan 2015 22:16

Ok, so here's my quandary. Keflex is not supposed to be effective against Lyme (see quote below), and yet when I went on it for a week it flared every single one of my Lyme symptoms so badly I was debating checking into the ER. I was placed on a week of it due to my lymph nodes in my armpits starting to swell up a month after I started rifampin. My doc agrees with the excerpt below that it shouldn't have worked on Lyme, and yet doesn't know what it would have worked on to cause a reaction like that. I was deemed the most interesting case of the week and seemed to stump everyone.

They retested me for all the co-infections and other infections right before this and everything comes back "negative".
They also passed around the idea of a bartonella like organism due to the bart-like rash I had after being on levofloxacin, but I don't test positive for bartonella henselae or quintana (but perhaps not because of the IgG deficiency). So even if it was bartonella and I'm just not testing positive, I don't find much good documentation that Keflex is effective against bartonella either. It seems so bizarre to me, that it would flare every single Lyme symptom, but not work on Lyme.

Keflex brought back every symptom full force that I went through the first month after the tick bite, including:
Basilar meningitis
Severe headaches
Nausea (brain induced and not the stomach kind)
Light and sound sensitivity
Large spike in neuropathy, both feet and it came back in my right arm
Wakening multiple times in the night to urinate
Blurry vision
Jaw tightness
Right shoulder blade started to wing
Severe mood swings
Bloodshot eyes

I went through a smaller microcosm of this on rifampin that eventually subsided after two weeks, hence I am stumped. Symptoms all match with lyme, minus the bart-like rash on levofloxacin, but Keflex is not supposed to work well on either Lyme or bart.

An Update on the Diagnosis and Treatment of Early Lyme Disease:
“Focusing on the Bull's Eye, You May Miss the Mark”

Amber Stonehouse MD 1, James S. Studdiford MD, FACP 2 and C. Amber Henry MD 1

1 Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
2 Department of Family Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

It is important to note that the popular cephalosporin, cephalexin (Keflex), is not
effective in the treatment of LD, nor are any of the fluoroquinolone class (16, 17) (Table
Half of what you are taught is incorrect, but which half? What if there's another half missing?

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Re: Keflex/Cephalexin

Post by dlf » Wed 7 Jan 2015 0:00

As someone who is NOT a doctor/physician and who has absolutely NO credentials, I am wondering, are you also taking Grapefruit seed extract, even at a different time of day? It is a common add-on to Lyme protocols, that may not be considered when looking for a solution.

Prescrire Int. 2012 Dec;21(133):294-5, 297-8.
Grapefruit and drug interactions.
[No authors listed]
Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few reports involving severe clinical consequences have been published, they suggest that grapefruit juice should be avoided during drug therapy, especially when the drug has a narrow therapeutic margin or carries a risk of serious dose-dependent adverse effects. Patients should be informed of this risk whenever a drug is prescribed or dispensed.
AND SEE: ... ?f=6&t=613
posted by cave76

Grapefruit Juice Interaction
Grapefruit juice may seem like an unlikely culprit to intervene with medications, but there are a few situations to be wary of.
• Cephalosporins. Reports have confirmed that co-administration of cyclosporin and grapefruit juice increases cyclosporin absorption.

Mean trough levels of cyclosporin have been reported to increase by approximately 25%. Grapefruit juice ingestion with cyclosporin has been shown to increase total cyclosporin absorption (area under the curve) by 16% to 200% compared with water or orange juice.

Peak serum levels of cyclosporin were 24% higher in patients ingesting the drug 90 minutes after intake of grapefruit juice as compared to ingestion with water. In patients who previously ingested cyclosporin with grapefruit juice, taking the drug with water resulted in lowering cyclosporin serum levels.
Because cyclosporin is a drug that’s titrated within a “therapeutic window,” patients should just avoid taking this drug with grapefruit juice. In fact, because grapefruit juice can affect the absorption of other drugs, it’s best to just have your patients avoid taking it with any medication just to be safe.
If the answer is yes, could you be having an overdose drug reaction?

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Re: Keflex/Cephalexin

Post by velvetmagnetta » Wed 7 Jan 2015 2:20

That first study dif posted, the one with "no authors listed", sounds like it was written by the Orange Juice Industry. ;)

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Re: Keflex/Cephalexin

Post by hv808ct » Wed 7 Jan 2015 3:31

Post by ChronicLyme19 » Tue 6 Jan 2015 22:16

Ok, so here's my quandary. Keflex is not supposed to be effective against Lyme (see quote below), and yet when I went on it for a week it flared every single one of my Lyme symptoms so badly I was debating checking into the ER.
Here’s a radical thought: maybe you don’t have an infection of any kind—“They retested me for all the co-infections and other infections right before this and everything comes back "negative"”—and you are simply experiencing the side effects of a powerful drug you shouldn’t be taking. Not every symptom is a “Lyme symptom” and not everyone who thinks they have Lyme disease does. ... center.htm

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Re: Keflex/Cephalexin

Post by RitaA » Wed 7 Jan 2015 9:56


I'm so sorry to hear that you are feeling unwell. Experiencing a return of your Lyme disease symptoms must be very disheartening, to say the least.

According to the following article abstract, combining Rifampin and Keflex (cephalexin) may increase the effects (and I'm guessing the side effects) of one or both medications in some individuals. If medication side effects are playing a role in your current symptoms, this is yet another factor that your medical team needs to consider:
Clin Pediatr (Phila). 1996 Apr;35(4):205-8.

Addition of rifampin to cephalexin therapy for recalcitrant staphylococcal skin infections--an observation.

Feder HM Jr1, Pond KE.

Author information

1Department of Pediatrics, University of Connecticut Health Center, Farmington 06030-3960, USA.


We report two pediatric patients with recalcitrant staphylococcal infections whose infections resolved when rifampin was added to standard antistaphylococcal therapy. One patient had a post-varicella staphylococcal ulcerative lesion and did not respond to cephalexin alone but did respond when rifampin was added. A second patient had staphylococcal bullous impetigo and did not respond to dicloxacillin or cephalexin but did respond when rifampin was added to the cephalexin. If a patient fails to respond to traditional antistaphylococcal therapy, the addition of rifampin may be beneficial.

[PubMed - indexed for MEDLINE]

I'm including only a few of the possible side effects from both medications to give you an idea of what is contained in both rather long lists. ... de-effects

Side Effects

This drug may cause upset stomach, heartburn, nausea, menstrual changes, headache, drowsiness, or dizziness. If any of these effects persist or worsen, inform your doctor promptly.


Rifampin may infrequently cause serious liver disease. Though sometimes necessary to completely treat certain infections, combination treatment with other drugs (e.g., isoniazid, pyrazinamide) may increase this risk. Tell your doctor immediately if any of these unlikely but serious side effects occur: flu-like symptoms (fever, chills, headache, muscle aches), change in amount of urine, persistent nausea/vomiting, stomach/abdominal pain, dark urine, yellowing eyes/skin, mental/mood changes (e.g., confusion, unusual behavior), unusual tiredness, easy bruising/bleeding, small red spots on the skin, joint pain/swelling. ... ideeffects
Side Effects

List Keflex side effects by likelihood and severity.

The following side effects are associated with Keflex:

Infrequent side effects of Keflex:

Feel Like Throwing Up Less Severe

Rare side effects of Keflex:

Confused Less Severe
Dizzy Less Severe
Head Pain Less Severe
Joint Pain Less Severe
Low Energy Less Severe
Numbness and Tingling Less Severe
I do hope you feel better soon. Please keep us posted when you're feeling up to it.

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Re: Keflex/Cephalexin

Post by ChronicLyme19 » Wed 7 Jan 2015 14:13

Thanks for the input guys.

Well, I was put on the cephalexin by my primary care because my lymph nodes in my armpits were swelling and starting to get really painful. Primary care figured I had some infection either in my armpits, which it didn't look like, or caught some other infection. Pain and lymph node swelling was reduced within a day of taking the cephalexin. So hv808ct, that does seem to justify her putting me on it, as it did what it was intended to do. And if your next comment is that I shouldn't be on the other medications, they why do they keep the symptoms at bay and make me feel better over time? I hadn't changed any meds in a month when my lymph nodes started to swell, so we figured maybe it was unrelated to the Lyme/co infections.

I am on both, rifampin and grapefruit seed extract, so that certainly seems like it could have caused unusually strong adsorption of the cephalexin. Most of the symptoms seem they could caused by an overdose/drug reaction, except maybe two. Why the meningitis just at the base of my head? Why not my whole head? Also, why the scapular winging? Maybe the inflammatory response it triggered just then aggravated the old injuries from the Lyme? But then if it was an allergic response to the drug, why not other classical allergy symptoms like hives, itching, throat swelling etc.

This is what I think makes it hard, how would you tell the difference from an OD triggering an inflammatory response that aggravated old injuries, vs. a Lyme herx? How would one tell the difference in what the inflammatory response was to?

This set of symptoms is EXACTLY what I went through when I first got bitten by the tick (minus the peripheral neuropathy as that came later), and at that time I wasn't taking ANY medication. My LLMD said he didn't think it was a drug reaction, and the second LLMD seemed to agree. Going into the neurologist today for another follow up about the winging (still trying to determine the exact cause of that). We'll see if he thinks a drug reaction could have caused the flare.

I think the hard part is telling what I'm reacting to, how do you tell the difference between a drug reaction, a lyme flare, or a reaction to a secondary infection. If it was a drug reaction, then it would cause the exact same pattern as the Lyme flare.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

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Re: Keflex/Cephalexin

Post by ChronicLyme19 » Thu 8 Jan 2015 19:49


-Lyme docs agree Keflex should not work on Lyme, and think maybe I have some secondary infection, but don't know what.
-Neurologist thinks it probably was a drug reaction, and that it flared all the Lyme symptoms because serum sickness can aggravate all your nerves. Sends me to an immunologist to confirm with skin testing. Says to come back if skin testing is negative, to help figure out if it was Lyme or a secondary infection instead.
-Local immunologist doesn't think it was a drug reaction, thinks skin testing won't be helpful. Says to stay off Keflex, and will chat with other 3 docs. Definitely wasn't a typical allergic reaction to cephalosporins or penicillins. Doesn't think it's worth risking doing an oral challenge.

Going into the city tomorrow to get a 4th opinion from my usual immunologist.

I'm still leaning towards drug reaction only because of one thing I just remembered. When I was in for an EMG the week on Keflex, the testing doctor pointed out my arm was unusually bright red where I had scratched it and asked if I had Dermatographic urticaria. I don't remember scratching it or being itchy that week and didn't think anything of it until it popped back into my head yesterday.

The fun part is the Lyme docs have been debating putting me on IVs because of the suspected spinal accessory nerve issue, but only if it's on the part that's inside your brain. They have yet to determine where the nerve issue is, if it's permanent damage, or the nerve is being pressed on from inflammation or lesion. My shoulder started to wing the week I was on Keflex as well as flare all my other neuro lyme symptoms, so I think it's safe to say that yes, the back issues are a nerve problem and not a muscle problem.
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Re: Keflex/Cephalexin

Post by ChronicLyme19 » Thu 8 Jan 2015 21:36

Scratch that, Keflex DOES work against Lyme (at least in vitro), but you just need really high concentrations of it compared to rocephin. I'm wondering, because I was on rifampin and GSE if those would be enough to increase the absorption of Keflex to the point at which it would be able to kill Lyme and cause a herx. Also, if you look at the table, there seem to be some variation on antibiotic susceptibility that varies by strain.

Title: In Vitro Susceptibilities of Borrelia burgdorferi to Five Oral Cephalosporins and Ceftriaxone
Microbiology Research Laboratory, Gundersen Medical Foundation, 1 and Infectious Disease Section,
Gundersen Clinic, 2 La Crosse, Wisconsin 54601, and Department of Bacteriology, University of Wisconsin,
Madison, Wisconsin 53706
Received 21 January 1992/Accepted 25 May 1992
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 1992, p. 1788-1790 ... 2-0222.pdf
In this study, the oral cephalosporins cephalexin, cefadroxil, and cefaclor did not appear suitable for Lyme
disease therapy because of their MICs, which were approximately equal to or significantly above concentrations in
serum achieved with oral administration (approximately 23 to 39 p,g/ml), and short serum half-lives (0.5 to 2 h).
After scanning other forums, there are plenty of reports of folks going on Keflex and having large spikes in Lyme-like neurological symptoms.
Last edited by ChronicLyme19 on Fri 9 Jan 2015 4:20, edited 2 times in total.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

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Re: Keflex/Cephalexin

Post by RitaA » Fri 9 Jan 2015 0:37

Hi ChronicLyme19,

Thanks for the updates. Your posts could very well help other folks in a similar situation now or in the future. It's reassuring to know you have access to doctors who are doing their best to figure things out.

It sounds like the immunologist you saw is erring on the side of caution by recommending you discontinue the Keflex instead of further challenging your body (which is already dealing with more than enough).

As you mentioned previously, there are times when it is virtually impossible for patients and their doctor(s) to tell the difference between a temporary reaction to a medication (which may signal it is working) or an adverse reaction that could potentially get worse with continued use. A true allergic reaction isn't always that easy to spot either because the spectrum includes everything from a slightly annoying rash to life-threatening anaphylactic shock.

Cephalexin (Keflex) is a first generation cephalosporin, whereas Ceftriaxone (Rocephin) is a third generation cephalosporin, and this apparently makes a difference. ... orins.html

SPECTRUM OF ACTIVITY. Gram-positive aerobic cocci: Very active against Streptococci pyogenes (Group A strep), Streptococcus agalactiae (Group B strep), viridans streptococci. Methicillin-resistant Staphylococci, Enterococci, penicillin-resistant Streptococcus pneumoniae are resistant.

Gram-negative aerobes: Commonly active against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae, though susceptibilities may vary. Inadequate activity against Moraxella catarrhalis and Hemophilus influenzae.

Anaerobes: Active against most penicillin-susceptible anaerobes found in the oral cavity, except those belonging to the Bacteroides fragilis group.

GENERAL CLINICAL USES. Uncomplicated, community-acquired infections of the skin and soft tissue and urinary tract. Useful for respiratory tract infections caused by pencillin-sensitive Streptococcus pneumoniae but not for Hemophilus influenzae and Moraxella catarrhalis. While effective for these infections, other less expensive alternatives should be used when appropriate because of their efficacy and narrower spectrum of activity (eg: penicillins, trimethoprim/sulfamethoxazole). Parenteral 1st generation agents are used for surgical wound prophylaxis.

Improved activity against Enterobacteriaceae associated with hospital-acquired infections; some agents are also active against Pseudomonas aeruginosa which is a frequent cause of hospital-acquired pneumonia.

SPECTRUM OF ACTIVITY. Gram-positive aerobic cocci: Cefotaxime, ceftriaxone, and ceftizoxime are active against methicillin-susceptible Staphylococcus aureus (though less than 1st and some 2nd generation agents), very active against Groups A and B streptococci, and viridans streptococci. Cefotaxime and ceftriaxone are more active than ceftizoxime against Streptococcus pneumoniae, particularly intermediately-penicillin resistant Streptococcus pneumoniae. None are active against methicillin-resistant Staphylococci, Enterococci, and Listeria monocytogenes.

Gram-negative aerobes: Very active against Hemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, and Enterobacteriaceae (eg: Escherichia coli, Klebsiella species, Proteus mirabilis, Providencia)found in hospital and community-acquired infections. Some Enterobacter species have a tendency to become resistant during cephalosporin therapy, and thus cephalosporins are not the drugs of choice for Enterobacter infections.

Only and ceftazidime and cefoperazone are active against Pseudomonas aeruginosa, and ceftazidime is preferred because it is more potent than cefoperazone against gram-negative bacteria.

Anaerobes: Cefotaxime, ceftriaxone, and ceftizoxime are adequate for oral anaerobes.

GENERAL CLINICAL USES. For infections involving gram-negative bacteria, particularly hospital-acquired infections or complicated community-acquired infections of the respiratory tract, blood, intra-abdominal, skin and soft tissue, and urinary tract. Because of their activity includes the aerobic gram negative bacteria covered by aminoglycosides, they may be an alternative to aminoglycosides in some patients with renal dysfunction.

The clinical situations requiring use of 3rd generation cephalosporins are likely to be encountered in patients who are hospitalized, have recently received antibiotics, or are immunocompromised.

A. Cefotaxime (Claforan), Ceftriaxone (Rocephin), Ceftizoxime (cefizox) . IV/IM formulations. Activity against Enterobacteriaceae (eg: Escherchia coli, Klebsiella pneumoniae) are similar. None are active against Pseudomonas aeruginosa. Only cefotaxime and ceftriaxone achieve adequate drug levels in the cerebral spinal fluid to constitute reliable empiric therapy for bacterial meningitis. Ceftriaxone is eliminated to a significant degree by the biliary system, and as a result, biliary pseudo-lithiasis has been reported as a side effect of this agent.
The following article abstract explains why cephalexin (Keflex) is not recommended for the treatment for Lyme disease:
Arch Fam Med. 2000 Jun;9(6):563-7.

Failure of treatment with cephalexin for Lyme disease.

Nowakowski J1, McKenna D, Nadelman RB, Cooper D, Bittker S, Holmgren D, Pavia C, Johnson RC, Wormser GP.

Author information

1Division of Infectious Diseases, Westchester Medical Center, New York Medical College, Valhalla, USA.

Lyme disease typically presents with a skin lesion called erythema migrans (EM), which though often distinctive in appearance may be confused with cellulitis. The first-generation cephalosporin, cephalexin monohydrate, is effective for treating bacterial cellulitis but has not been recommended or studied for treating Lyme disease because of poor in vitro activity.

To describe the outcome of patients with EM who were treated with cephalexin.

Patients presenting with EM to the Lyme Disease Diagnostic Center in Westchester, NY (May 1992-September 1997). A 2-mm punch biopsy specimen of the leading edge of the EM lesion and/or blood was cultured for Borrelia burgdorferi.

Eleven (2.8%) of 393 study patients had been initially treated with cephalexin prior to our evaluation; 9 (82%) were originally diagnosed with cellulitis. Cephalexin was administered for 8.6 days (range, 2-21 days) prior to presentation. All 11 patients had clinical evidence of disease progression, including 8 whose rash enlarged, 2 who developed seventh-nerve palsy (1 with new EM lesions), and 1 who developed new EM lesions. Borrelia burgdorferi grew in cultures from 5 patients despite a mean of 9.8 days of treatment with cephalexin (range, 5-21 days).

Cephalexin should not be used to treat early Lyme disease and should be prescribed with caution during the summer months for patients believed to have cellulitis in locations where Lyme disease is endemic.

[PubMed - indexed for MEDLINE]
My guess is that the precise reason(s) for the flare in symptoms experienced by Lyme disease patients prescribed Keflex (yourself included) may never be known with any certainty -- and especially since the reason(s) could well vary from person to person.

I think it's worth noting that people react differently to medications for a variety of reasons, further complicating matters:

Definition : "Study of hereditary sources of variation in drug response, their prevalence and mechanism."


Patients vary widely in their responses to drugs. Important factors in variability are drug metabolism and drug transport. Interindividual variation of drug metabolism is due to several factors. Genetic polymorphism is one of them and is defined by the presence, in a normal population, of monogenic traits that exist in at least two phenotypes, neither of which is rare (less than 1%).

Genetic polymorphism of metabolic enzymes may be due to:

- Allelic variants that lead to enzymes with different catalytic activities from that of the wild type form.
- Gene suppression.
- Gene duplication.
- Modification in gene inducibility.

Genetic variability has been historically illustrated by the metabolism of isoniazid. Isoniazid is primarily acetylated in the liver to N-acetylisoniazid, a precursor of a hepatotoxic compound. Large genetically controlled ethnic differences exist in the distribution of acetylator status (slow and rapid acetylators). Adverse effects may occur prevalently in slow acetylators. On the other hand, rapid acetylators may be more susceptible to adverse reactions such as isoniazid-induced hepatic damage. Later on, it has been found that the majority of metabolic polymorphisms involve the isoenzymes of the cytochrome P450 system.

Clinical implications

The clinical implications of genetic polymorphism in drug metabolism depend on whether activity or toxicity lies with the affected substrate or the metabolite, as well as the importance of the pathway to overall elimination. If the parent drug is active, there is a greater likelihood of adverse reactions in poor metabolizers and ineffective therapy in extensive metabolizer. Likewise, if the metabolite is active or toxic, there is a greater likelihood of adverse reactions in the extensive metabolizers and ineffective therapy in the poor metabolizers.

Genetic variability may effect drug clearance but also drug bioavailability ...
I wish you the best of luck in figuring this out with the help of your medical team. Most of all, I hope you are feeling better soon.

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Re: Keflex/Cephalexin

Post by velvetmagnetta » Fri 9 Jan 2015 5:04

How sure are you that you should be experiencing a Herx reaction? Does anyone know for certain that the pain experienced by Lyme patients on antibiotics is from a bacterial die-off?

After years of agonizing pain, thinking this pain was somehow good for me, I have come to the conclusion that the Herx is a Hoax and that the pain we feel from certain drugs is not a good sign and that it is in fact dangerous and possibly life-threatening. At the very least, it is probably causing some kind of nerve, muscle, or tissue damage.

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