Multiple use of antibiotics

In the feature article “Intracellular Activity, Potential Clinical
Uses of Antibiotics” Robert M. Rakita (ASM News, 64, 570, 1998)
discusses the three-way interaction of the pathogens, host defense
cells, and antimicrobial agents, especially inside the neutrophils
and macrophages. The preparation of newer macrolide and
quinoline antibiotics try to achieve higher intracellular levels with
greater antimicrobial activities and with minimal cellular damage.
The goal being the control and elimination of the infecting bacteria.
What is often over-looked is the broad cellular reactions of
antibiotics in addition to their antimicrobial and clinical response.
Inhibiting a pathogen’s growth with antibiotics usually includes
the inhibition of cellular protein synthesis while its elimination
depends on its intracellular location and the host’s immune
responses. Many more conditions can effect the reactivity of
pathogens and antibiotics in the complex host tissues than in the
controlled in-vitro Tissue Cell Cultures. The variable tissue
pathogenicity also contributes to the variable antibiotic sensitivity
requiring adjustments for each pathogen and their tissue
location.(1)
Prior to the availability and application of antibiotics for the
control of diseases, gold salts, arsenicals, sulfa drugs and other
various chemicals were used to ward off the offending bacterial
pathogens without killing the patient. The clinical application of
antibiotics started in the early ‘40’s when penicillin became
available during WWII as the first miracle drug from a penicillium
mold. A few years later when the broad spectrum tetracycline
antibiotics became available their clinical use spread like a gold
rush. The bacterial sensitivities and potential clinical application of
the new antibiotics were extensively used by clinics and
laboratories. The choice of antibiotics was made after the isolation
and identification of the infecting agent. The development of
allergies and toxicities to some antibiotics limited their use in some
patients. Microcidal penicillins inhibit bacterial cell wall synthesis,
whereas the tetracyclines (macrolides) are micro static inhibiting
protein synthesis and the growth of the wall-less bacteria such as
mycoplasmas.
The initial use of high dosage antibiotics in some chronic
disease patients may cause a flare or clinical worsening with a
serologic rise in antibody titer to a suspected microbial agent such
as mycoplasmas. A temporary flare of symptoms following
antibiotic treatment is often referred to as a Jarisch Herxheimer
reaction. The flares often occur in joints or areas that have been
quiet or dormant since the arthritis was first observed. Knowing
this the patients are encouraged by the temporary worsening
following their antibiotic treatment. The delayed reaction resulting
from the release of microbial antigen into the sensitized host tissue
as in a “Graft vs. Host” reaction that is not a drug sensitivity.
Similarly the occurrence of physical &/or mental stress could also
initiate clinical worsening with a rise in microbial antibody titer.
The flare reaction could also result from the released microbial
antigen complexing with its circulating antibodies to promote
Complement Fixation. The antibiotics, tetracyclines, can also act
like the immunosuppressant steroids by blocking the formation of
the antibiotic+antigen complex that initiates inflammation. Many
clinical disorders are considered Immune Complex Diseases of
infectious origin, such as rheumatoid arthritis and Lupus, resulting
from the activation of complement and proteolytic destruction of
tissues with the deposition of Immuine Complex on the kidneys
and other tissue cell membranes.
The tetracycline antibiotics are potent metal chelating,
complexing, agents and comparable in action to the clinical use of
the chelating agents ethylenediaminotetraacetate, EDTA, and
penicillamine. Consequently the mode of antibiotic administration,
Intravenous or Oral (between meals), could have an affect on
the composition of their absorption state and thus their reactivity.
When complexed with divalent trace metals (Cu, Zn, Mg, Se, etc.)
The antibiotics become antioxidants or electron scavengers. As
such the metal antibiotic complex becomes antiinflammatory
neutralizing free oxygen radicals. By combining with metaloproteins
and metaloenzymes such as collagenase, antibiotic therapy can
inhibit collagen tissue destruction. If used excessively in high doses
the antibiotics, as protein synthesis inhibitors, could also inhibit the
synthesis and function of essential cellular proteins and not just the
pathogens.
Because of their immunosuppresive actions the macrolide
antibiotics can block and limit the immune complex (Antibody +
Antigen) formation and thus stop the complex induced
inflammation. In cases with low pathogenic activity, such as
mycoplasmas, pulsed antibiotic therapy with lower doses over
longer periods has proven more effective and with fewer side
effects. Tissue cells will survive intermittent (pulse) treatment of
tetracyclines but not constant exposure even at lower doses. In the
chronic immunologic disorders of probable infectious etiology
high daily antibiotic doses are not essential or effective for the less
virulent agents.
Bioassays for antibiotic levels in blood and tissues measures
the antimicrobial action that would not explain their other activities
based on intracellular concentration.
Although suspected of infectious origin the clinical trials of
minocycline antibiotic in rheumatoid arthritis was based primarily
®
Medical data is for informational purposes only. You should always consult your family physician, or one of our referral physicians prior to treatment.
on its inhibitory action of the metalloenzyme, collagenase, that
destroys the connective tissues and joint cartilage causing the
inflamed joints.
The effectiveness of treatment with minocin antibiotic was
based primarily on the eradication of arthritis inflammation rather
than infectious agents. The maximum effectiveness of the
antibiotic treatment was found in the duration of therapy indicating
a slow healing process that has to balance cell growth versus
inhibition of protein synthesis and microbial growth by the
multiple antibiotic actions. Growth inhibiting antibiotics may
control mycoplasma or microbial growth for an indefinite period
until the neutralizing antibodies and immune system process their
elimination.
Antibiotics can be used in the identification of the infectious
bacterial agent(s). In cases where the agent can not be isolated and
identified or the DNA can not be matched it is possible that
antibiotic therapy will cause the release of the microbial antigen to
initiate a specific antibody response. The serologic measure of a
change or response in the serum antibody level to a bacterial
infection would indicate its presence. The sero conversion or the
increase in antibody titer, resulting from the administration of a
vaccine would indicate the host’s immune responsiveness to a
particular antibiotic therapy. The specificity and sensitivity of the
serologic response depends on the test used, such as: growth
inhibition, neutralization, agglutination (ELIZA), complement
fixation, immunoblotting.
A rise in serum antibody level during the acute to convalescent
phase on antibiotic therapy would indicate a concurrent infection or
the antigen release from a persisting silent infection. A similar
positive sero conversion with a rise in antibodies could be observed
in a patient following physical or mental stress. No rise in antibody
titer to a vaccine, infection or stress would indicate an
immunodeficient agammaglobulinemia subject with limited
antibody production and immune defence. In rheumatoid arthritis
and other infectious diseases that initiate the anti-antibody response
(rheumatoid factor) RF the antibody levels are inversely related
causing an apparent decrease or negative sero conversion.
Following antibiotic treatment when the mycoplasma antibody
level increases, the RF test results will be lower.
The use of generic antibiotics may have the same
antimicrobial potency while their systemic action in the host may
varay significantly. For example in the treatment of RA the generic
minocycline is reportedly less effective than minocin. In some
patients this difference in antibiotic action could result from patient
differences.