The rationale for the use of gentamicin for short term, empiric therapy is different than it is for long term definitive therapy:
If a person presents in an emergent manner with a fever, high white cell count, and other signs or symptoms of an infection (for example septicemia-a blood infection) the person must be aggressively treated with strong, broad spectrum antibiotics until blood cultures are obtained. Blood cultures are grown to determine which specific bacteria are causing the infection, and which antibiotics are effective against these bacteria. Generally, antibiotics must be given for two-three days before these culture results are available. Because the side effects of gentamicin are minimal when given for a very short period, its use in empiric situations for two-three days is much more justifiable than its use in definitive therapy requiring long term administration.
Culture and sensitivity studies can reveal, in many instances, the pathogen that is causing the infection, and the antibiotics to which the pathogen is sensitive.
The results are sent to the treating physician in a report listing various antibiotics and whether that bacteria is resistant or susceptible to that particular antibiotic: (Figure 1).
Figure 1. Example of culture and sensitivity report
The treating physician uses this information, preferably combined with other clinical information regarding the presentation of the infection and information regarding the particular patient, to arrive at a rational choice for an antibiotic or combination of antibiotics to use. Even though a particular pathogen is shown by culture (in vitro) to be sensitive to a particular antibiotic, its rational use may be totally contradicted by the presentation of the infection or by host factors (characteristics of the patient)
Gentamicin is used as a primary antibiotic or it is used synergistically with other antibiotics:
Aminoglycosides, including gentamicin, can be used as a primary agent against a specific organism or organisms, or can be used synergistically with another antibiotic to “boost” the efficacy of the other antibiotic. This distinction is important, because synergistic doses tend to be much lower (usually less than 3 mg/kg/day), potentially causing fewer side effects. When gentamicin is used as primary therapy, the dosing tends to be higher (4-7mg/kg/day) potentially causing greater side effects.
Use of gentamicin as a primary antibiotic agent:
While still an important antibiotic under certain circumstances, there are only a few instances where the use of gentamicin may be justified outside of short-term empiric treatment. Because of the risk of nephrotoxicity, ototoxicity, and vestibulotoxicity associated with the use of aminoglycosides, and because ototoxicity and vestibulotoxicity are usually permanent and life altering, gentamicin can be only justified as a primary antibiotic agent when there are no reasonable alternatives available. In the past 25+ years, many antibiotics have been developed that are equally or more efficacious than gentamicin as primary antibiotic agents.
Often, physicians will just look at a sensitivity report and pick an antibiotic without giving sufficient consideration to side effects or host factors that may preclude its use. For example, Staphylococcus aureus will often show sensitive in vitro when tested against gentamicin. Gentamicin is now considered a third rate agent to use against Staph.
Gentamicin should be used for primary therapy only when there is no other viable alternative treatment. Regardless of the expense of other antibiotic agents, there is no justification for subjecting a patient to the possibility of permanent vestibular loss unless gentamicin is the only antibiotic that would be effective against a particular organism.
Moreover, the use of gentamicin in these circumstances must also depend on how serious the infection is. We have represented several clients who developed lifelong, severe vestibulopathy because a physician used gentamicin to preserve a toe. Amputation of the toe would have had a miniscule impact on each of these individuals when compared with the devastating impact of gentamicin poisoning.
Gentamicin is no longer the "big gun" for pseudomonas infections:
In recent years, newer, less toxic anti-pseudomonas drugs have emerged that in most instances are equally or more efficacious than gentamicin. Ceftazidime (fortaz, Tazicef, tazidime), piperacillin-tazobactam (Zosyn) and imipenum (Primaxin) are examples. The following is excerpted from Mandell, Bennett, & Dolin: Principles and Practice of Infectious Diseases, 6th ed at p. 2601: "Thus, none of the dogmas concerning the appropriate therapy for P. aeruginosa bacteremia can be considered to be established by blinded, controlled clinical studies. One firm conclusion appears to be that monotherapy with an aminoglycoside dosed in the approved way should not be the primary choice for antibiotic treatment. Unquestionably, the majority of infectious disease experts still favor the use of combination therapy for P. aeruginosa bacteremia. However, it is difficult to indict the use of a single modern anti-pseudomonas-lactam antibiotic as being inadequate therapy. Even in the patients most at risk for dying rapidly from P. aeruginosa bacteremia (i.e., high-risk patients with fever and neutropenia), empirical monotherapy [referring to the anti-Pseudomonas-lactam antibiotics such as ceftazidime, piperacillin-tazobactam, or imipenum] designed to treat P. aeruginosa is considered to be as efficacious as empirical combination therapy in the Practice Guidelines of the Infectious Diseases Society of America (IDSA)."
Use of gentamicin with another antibiotic for synergistic effect:
Another dosing issue relates to the concept of antibiotic synergy. Gentamicin kills bacteria by interfering with the bacteria’s ability to synthesize protein.
Specifically, gentamicin binds tightly to ribosomes, which are located inside of the cell. Other antibiotics, including penicillin-like antibiotics, (beta-lactam), kill bacteria by interfering with cell wall synthesis, making the cell wall porous. When combined with gentamicin, the beta-lactam allows a lot more gentamicin to get inside the cell to attach to the ribosomes, which means that a lower concentration of gentamicin is needed to give the same bacteria-killing effect than without the beta-lactam.
Only certain organisms such as Pseudomonas aeruginosa and certain enterococcal species exhibit synergistic killing with the addition of an aminoglycoside to other antibiotics.
There is no possible way to describe or delineate herein every appropriate or inappropriate choice of antibiotic for your infection. For this reason, if you have any questions regarding the choice of drug or any other aspects of your treatment surrounding aminoglycosides, you should contact our office today.
Keith S. Douglass & Associates, LLP
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