Amoxicillin for dental infection

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National Center for Agricultural Utilization Research: Peoria, IL.

Large-scale commercial production of penicillin during the 1940s opened the era of antibiotics and is recognized as one of the great advances in civilization. The discovery of penicillin and the recognition of its therapeutic potential occurred in England, while discovering how to mass-produce the drug occurred in the US -- at the Peoria lab.

Penicillin was discovered in 1928 by bacteriologist Alexander Fleming, working at St.

It was not until 1939 that a group of scientists at England's Oxford University began intensive research and was able to demonstrate penicillin's ability to kill infectious bacteria.

As the war with Germany continued to drain industrial and government resources, the British scientists could not produce the quantities of penicillin needed for clinical trials on humans and turned to the United States for help. They were quickly referred to the Peoria lab where scientists were already working on fermentation methods to increase the growth rate of fungal cultures. Arriving on July 14, 1941, work on the challenge began the very next day. Pumping air into deep vats containing corn-steep liquor (a non-alcoholic by-product of the wet milling process) and adding other key ingredients was shown to produce faster growth and larger amounts of penicillin than the previous surface-growth method.

Ironically, after a worldwide search, a strain of penicillium on a moldy cantaloupe from a Peoria market was found to produce the largest amount of penicillin when improved and grown in deep-vat, submerged conditions. Production methods and samples of the new strain were transferred both to other research groups and private industry and clinical trials were performed in 1943.

When the trials showed that penicillin was the most-effective antibacterial agent to date, penicillin production quickly was scaled up and the antibiotic was made available in quantity to treat Allied soldiers wounded on D-Day. As production increased, the price dropped from nearly priceless in 1940, to $20 per dose in July 1943, to $0.55 per dose three years later.

The acceleration of penicillin production was one of the most successful achievements of American chemists and chemical engineers, establishing the production of antibiotics and fostering today's pharmaceutical industry. While it was often called the "wonder drug" because of its effectiveness, one of penicillin's true wonders was the short development time from recognizing its value to mass availability.

Three members of the British group were awarded the Nobel Prize as a result of their work. Moyer of the American team was inducted into the Inventors Hall of Fame.

In 2001, NCAUR was designated by the American Chemical Society and Royal Chemical Society as an International Historic Chemical Landmark in recognition of its significant role in the development of penicillin. In this section we provide tips on the usage of various standard antibiotics for Lyme disease as well as less standard ones. We also review other treatment approaches for pain, fatigue, insomnia, memory, and mood.

We refer the reader to other sources that describe why patients might have persistent symptoms and other treatment options (e.g., in portions of our book Conquering Lyme Disease: Science Bridges the Great Divide ).

Here we simply wish to provide some important facts that people should know about various treatments. Doctors are taught in medical school: "Above all due no harm". However, nearly all treatments have both benefits and risks.

Therefore prior to any thereapeutic

intervention

When considering treatment options for Lyme disease, patients should find out how well studied these treatment are, whether they have been shown to be effective, and what the side effects are. Patients should also keep an open mind regarding what might help as some symptoms may reflect active infection (and therefore benefit from antibiotics) while others may reflect the residual effects on the body of the prior infection (and therefore require non-antibiotic approaches). The goal is to restore one's health and functional status so as to maximize quality of life.

As with all recommendations on this website, the taking of over-the-counter or prescribed medications should be carefully reviewed with a physician to ensure safety and efficacy and to assess for potentially harmful drug interactions.

Pregnant women in particular should check with their physician; a good website to check for for drug interactions is "Mother to Baby". The three first-line oral antibiotics for Lyme disease include doxycycline (Monodox, Doryx, Vibramycin, Oracea), amoxicillin (Amoxil), and cefuroxime (Ceftin, Zinacef).

Ceftriaxone (“Rocephin”) administered intravenously is the preferred antibiotic for neurologic Lyme disease in the United States. Amoxicillin (Amoxil) Amoxicillin is a broad spectrum bacteriocidal antibiotic that works by inhibiting cell wall synthesis. This a medicine that requires 3x daily dosing; it is important to maintain frequent dosing in order to keep the blood levels of the antibiotic high enough to be effective.

Amoxicillin is often prescribed to children under age 8 and to pregnant women who get Lyme disease.

Augmentin is a combination medication that includes both amoxicillin and the enzyme inhibitor clavulanate that allows the amoxicillin to be more effective against other penicillin-resistant microbes; a downside of this combination is that it might cause signfiicantly more gastrointestinal disturbance than plain amoxicillin. Most studies have found plain amoxicillin to be highly effective against Borrelia burgdorferi and thus the combination (Augmentin) is not needed. Note: If you are allergic penicillin or to cephalosporins, then there is a good chance you may develop an allergic reaction to amoxicillin. A

severe

Cefuroxime (Ceftin) Cefuroxime, a bacteriocidal 2nd generation cephalosporin, is FDA approved for the treatment of early Lyme disease.

Cefuroxime works by disrupting cell wall synthesis and does cross the blood brain barrier to some extent.

(The term “generation” when applied to cephalosporins simply refers to when the drug was developed and generally means that the “later” generation versions have a longer half-life (so they don’t need to be taken as frequently) and have better efficacy and safety.) Cefuroxime should be taken with food in twice daily dosing.

Note: if one is penicillin allergic, there may be an increased risk of developing an allergic reaction to cefuroxime. Doxycycline (Doryx, Monodox) Doxycycline is considered the first-line drug of choice for Lyme disease by most physicians.

Doxycycline, a bacteriostatic antibiotic, has the advantage of twice daily dosing and effectiveness not only for Lyme disease but also for some other tick-borne diseases such as borrelia miyamotoi disease, ehrlichiosis, anaplasmosis, tularemia, and rocky-mountain spotted

fever

In Europe, doxycycline is considered to have comparable efficacy for neurologic Lyme disease as intravenous ceftriaxone; this has not yet been examined in the United States however and may not apply to U.S.

neurologic Lyme disease as the genospecies causing neurologic Lyme in the US is B.burgdorferi while in Europe it is most commonly caused by B.garinii.

Doxycycline absorption is decreased by food and milk and especially decreased by antacids or laxatives that contain calcium, magnesium, or aluminum or vitamins that contain iron.

The latter medications or vitamins should be taken 6 hours before or 2 hours after the doxcycline.

Note 1: Doxycycline raises the risk of sunburns due to increased skin sensitivity to sunlight.

Doxycycline side effects include moderate to severe gastric symptoms (nausea, vomiting, diarrhea), vaginal yeast infections, decreased effectiveness of birth

control

Doxycycline should not be combined with the acne drug isotretinoin as that will increase the risk of elevated intracranial pressure (and the potential for vision loss).

Note 2: Use of any tetracycline-class agent (like doxycycline) with alcohol may lead to a bad reaction with symptoms such as headaches, nausea, vomiting, confusion, and flushing.

Note 3: Doxycycline is contra-indicated in pregnancy. Previously its use was discouraged in children under age 8, but the American Academy of Pediatrics has recently revised their guidelines to allow use. Note 4: Patients on blood thinners (anti-coagulants) should be aware that doxycycline can lead to an enhancement of the anti-coagulant effect, possibly increasing the risk of bleeding. The impact of anti-coagulants while on doxycycline should be monitored by the health care provider. Ceftriaxone (Rocephin) Ceftriaxone is a third generation cephalosporin and, like other cephalosporins, is bacteriocidal. Individuals with neurologic Lyme disease, cardiac Lyme disease, or Lyme arthritis that hasn’t responded well to oral antibiotic treatment will often be given intravenous ceftriaxone.

Ceftriaxone has excellent penetration of the blood-brain barrier and is one of the most effective drugs for Lyme disease.

Ceftriaxone is typically given once a day intravenously, typically in 45 minutes.

While this can be administered in the doctor’s office on a daily basis through a peripheral vein, most commonly it is administered through a mid-line or a PICC line that once inserted can be accessed for the daily infusions at home (thereby eliminating the discomfort and inconvenience of daily needle sticks).

Note 1: Ceftriaxone can result in biliary sludging that in some patients leads to biliary stones and need for gall bladder removal; in our research study, one patient of 37 developed biliary stones ( 2.7%) which is similar to what has been reported in the literature.

Some doctors prescribe “Actigall” to dissolve biliary stone formation, especially if the patient is starting to complain of epigastric pain or nausea. Some doctors order an ultrasonogram of the gall bladder prior to initiating ceftriaxone therapy to identify those patients who might be at greatest risk of forming gall stones.

Note 2: While the ease of administration is enhanced when ceftriaxone is administered intravenously through a Mid-line or a PICC line, the presence of this indwelling line also increases the risk of systemic infection and serious blood clots.

Therefore, patients need to remember to flush their PICC or Mid-line daily, to keep the PICC line site clean, and to not engage in “jerky” arm movements, such as might occur when washing windows or playing tennis or golf.

IN the evaluation of the patient prior to insertion of a PICC line or a Mid-Line, the clinician order blood tests to determine if the patient is at higher risk of forming blood clots or inquire about one’s family history of blood clotting.

Note 3: Rarely ceftriaxone can trigger hemolytic anemia and pancreatitis.

Note 4: Cefotaxime (Clarforan) is also a 3rd generation intravenous antibiotic. While Cefotaxime is less likely to cause gallstones, it requires 3x daily dosing which for most patients is too difficult to maintain. Given that it is essential for efficacy that the drug be administered every 8 hours, cefotaxmine is less commonly used than ceftriaxone. Benzathine Penicillin (Bicillin-LA) Benzathine Penicillin is an intramuscular form of penicillin that has the advantage of being long-acting and allowing for consistently high blood and tissue levels of penicillin.

Early studies indicated that it was helpful for neurologic Lyme disease, but not nearly as effective as intravenous ceftriaxone (Rocephin). The blood levels after benzathine penicillin are almost as high as after IV ceftriaxone.

Because of the intramuscular administration, the risk of gastrointestinal side effects and yeast infections are lower than with oral antibiotics.

Note: In most individuals Bicillin is self-administered, often in the muscle of the buttocks. A lidocaine-like anesthetic cream can be applied topoically30-60 minutes before to reduce the injection site pain.

The downside to benzathine penicillin is that many people do not want to inject themselves.

Because once injected, it can’t be removed, it is important to make sure the individual is not allergic to this medication before initiating treatment.

Azithromycin and clarithromycin are macrolide antibiotics that have been studied in humans for the treatment of Lyme disease.

Both are better tolerated than the older macrolide antibiotic erythromycin in having fewer gastrointestinal side effects. Both azithromycin and clarithromycin are considered second-line agents for Lyme disease among individuals who cannot tolerate doxycycline, amoxicillin, or cefuroxime.

(Erythromycin is considered inferior to the other first line agents such as doxycycline or amoxicillin and is therefore not recommended as a primary agent for Lyme disease.) In addition to their benefits as antimicrobial agents, azithromycin and clarithromycin also have anti-inflammatory properties that can lead to symptom improvement. There are study design problems with the research studies of azithromycin and clarithromycin; therefore, it is hard to know whether they are truly less efficacious than the first-line agents for early Lyme disease.

Macrolides however should be used with caution given the risk of interaction with other medications.

The key to consider is that these antibiotics impact the liver enzymes that help to metabolize other medications; specifically they can affect the cytochrome P450 1A2 and 3A4 isoenyzmes.

For example, erythromycin or clarithromycin can lead to dangerously increased blood levels of the anticonvulsant drug carbamazepine (Tegretol) as well as increases in the anti-anxiety drug alprazolam (Xanax). Erythromycin and clarithromycin can also lead to an increase in the blood levels of the anti-asthmatic drug, theophylline, which can put the patient at risk for seizures or arrhythmias. When macrolides are used with paroxetine (Paxil) – an anti-depressant drug, there may be an unexpected increase in the blood level of the parosetine due to the macrolide-inducted inhibition of the liver enzyme metabolism; this could lead to mania or serotonin syndrome.

These approaches are considered for those patients who have persistent symptoms that have not abated or resolved after antibiotic therapy.

When symptoms persist, it is very important to take a fresh look at the patient and determine whether other problems have emerged (possibly unrelated to Lyme disease) that may be causing the symptoms. For example, fatigue may be due to anemia or thyroid deficiencies. Numbness and tingling may be due to vitamin deficiency (B1, B6, B12), diabetes, carpal tunnel sydnrome, or autoimmune causes. While infection with Borrelia burgdorferi itself can cause many of the symptoms below and thus require antibiotic treatment, these symptoms may also be triggered but not sustained by the prior infection; this may be due to residual inflammation, ongoing immune activation, tissue damage, or neurotransmitter/neural circuitry changes. In this situation, symptom-based therapies can be quite helpful. Because the suggestions listed below have not yet been studied in clinical trials of Lyme disease , these suggestions are based on evidence obtained from other disorders with similar clinical features.

None of these treatments have been FDA-approved for the treatment of Lyme disease-related symptoms. Neuropathic pain (numbness, tingling, burning, shooting) and central "brain" pain syndromes can often be helped with agents such as gabapentin ("Neurontin") or pregabalin ("Lyrica").

There was a small open label trial

that