Gentamicin is no longer the "big gun" for Pseudomonal infections: In recent years, newer, less toxic anti-pseudomonal 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. [emphasis supplied] 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 antipseudomonal -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 antipseudomonal -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)."

However, gentamicin has recently been recognized as appropriate in the treatment of serious pseudomonal infections under certain circumstances. The following is excerpted from Giamarellou and Antoniadou, Antibiotic therapy - Antipseudomonal antibiotics, Med. Clin. N. Am. 85-1 (2001):

"Despite the advent of newer antipseudomonal compounds such as carbapenems and the fluoroquinolones, aminoglycosides have an important role in the therapy of serious P. aeruginosa infections. They continue to be used because of (1) their excellent and fast concentration-dependent bactericidal activity, a determining factor in the prognosis of severe P. aeruginosa infections in neutropenic patients or in ICU life-threatening nosocomial infections, particularly during the first 24 hours of treatment; (2) their limited tendency to develop resistance during therapy; (3) the synergistic effect when combined with antipseudomonal penicillins and antipseudomonal cephalosporins in vitro and in vivo; (4) the protective effect toward resistance development in the -lactams whenever they are given simultaneously in vivo; (5) their lack of inoculum effect; (6) their prolonged and concentration-dependent postantibiotic effect (> 2 hours); (7) their antimicrobial activity at levels below their MICs; and (7) the possibility to be given once daily despite a half-life that demands twice-daily or thrice-daily administration.[9] The last-mentioned possibility is based on their prolonged PAE and the first exposure effect (i.e., the down-regulation of subsequent uptake of the drug after initial exposure of bacteria to it). All aminoglycosides share the same disadvantages, however: (1) nephrotoxic, ototoxic, and neuromuscular blockade potential: (2) poor kinetics in cerebrospinal fluid, eye compartments, prostate, and phagocyte with an intracellular-to-extracellular ratio of less than 1; (3) reduced in vitro activity under modification of environmental factors, such as divalent caution concentration, acidic pH, decreased arterial oxygen tension, and microaerobic or anaerophilic conditions, as happens in abscesses; and (4) in vivo inactivation by high concentration of penicillins and cephalosporins."

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-lactams), 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 P. aeruginosa and certain enterococcal species exhibit synergistic killing with the addition of an aminoglycoside to other antibiotics. Gentamicin is most often used as a synergistic agent in the treatment of endocarditis.

Synergistic dosing is discussed here.

Antibiotic Mechanism of Action, General

• Antimicrobial Agents Used in Treatment of Infectious Disease. This is a short, comprehensive explanation of many of the aspects of antibiotic therapy.