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β lactam monotherapy versus β lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis

BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7399.1111 (Published 22 May 2003) Cite this as: BMJ 2003;326:1111

The dangers of broad spectrum antibiotics

EDITOR - The meta-analysis regarding b lactam monotherapy versus b
lactam-aminoglycoside combination therapy misses an important point.1 The
broad spectrum monotherapy endorsed is far more likely to select for
antimicrobial resistance than a combination regimen. Prescribers do not
always realise that giving a patient antibiotics not only affects that
patient and his environment, but also anyone else who comes into contact
with that patient and his environment.2

Antibiotics seriously disturb the normal intestinal flora. This
disturbance facilitates bacterial overgrowth with emergence of resistant
microorganisms. These organisms themselves can cause serious infections,
but they will also encourage the transfer of resistance factors to other
bacteria. The more broad spectrum an agent, the more effect it will have
on the intestinal flora. Carbapenems are associated with an increase in
hospital-acquired infections due to Stenotrophomonas maltophilia.3 This
particularly resistant Gram-negative organism will also overgrow in
response to treatment with third-generation cephalosporins, along with a
host of other pathogens, namely Clostridium difficile, multiply resistant
coliforms, methicillin-resistant Staphylococcus aureus (MRSA), yeasts and
enterococci.2 These may spread to other patients, cause outbreaks and
contaminate the environment long-term.

The risk of selecting resistant organisms is reduced by using a
combination of antibiotics, particularly b lactam-aminoglycoside
combinations.4 Such combinations also demonstrate synergistic bactericidal
activity.4 Whilst there may be little difference in outcome to an
individual patient, antibiotic prescribers have a duty to consider the
future treatment of infection, because we appear to be running out of
therapeutic options. The ecological benefits of narrow spectrum â lactam-
aminoglycoside regimens become even more attractive when managers realise
the cost-savings they represent.5

(1) Paul M, Soares-Weiser K, Leibovici L. â lactam monotherapy
versus â lactam-aminoglycoside combination therapy for fever with
neutropenia: systematic review and meta-analysis. BMJ 2003; 326:1111-5.

(2) Dancer SJ. The problem with cephalosporins. J Antimicrob
Chemother 2001; 48:463-78.

(3) Sanyal SC, Mokaddas EM. The increase in carbapenem use and
emergence of Stenotrophomonas maltophilia as an important nosocomial
pathogen. Chemother 1999; 11:28-33.

(4) Barriere SL. Therapy of choice for the empiric treatment of the
febrile neutropenic patient. Drug Intell Clin Pharm 1986; 20:767-9.

(5) Lemmen SW, Hafner H, Kotterik S, Lutticken R, Topper R.
Influence of an infectious disease service on antibiotic prescription
behaviour and selection of multiresistant pathogens. Infection 2000;
28:384-7.

Competing interests:  
None declared

Competing interests: No competing interests

27 May 2003
Stephanie J Dancer
Consultant Microbiologist
Scottish Centre for Infection & Environmental Health, Clifton House, Clifton Place, Glasgow G3 7LN