COLLATERAL DAMAGE IN GRAM NEGATIVE BACTERIA

Djoko Widodo
Division of Tropical Medicine and Infectious Diseases
Department of Internal Medicine Faculty of Medicine University of Indonesia /
Cipto Mangunkusumo National Referral Hospital

C ollateral damage is a term used to refer to ecological adverse effects of antibiotic therapy; namely,
the selection of drug-resistant organisms and the unwanted development of colonization or
infection with multidrug-resistant (MDR) organisms. The risk of such damage can be assessed for
different antibiotic classes by a variety of epidemiologic studies. Resistance to cephalosporins in
Enterobacteriaceae is a critical problem in the Asia Pacific Region. Resistance is driven by usage of the
3rd generation cephalosporins. The presence of an ESBL-producing organism in an infection can lead to
increased morbidity and mortality. The threat of the presence of an ESBL-producing organism in an
infection may accelerate the early usage of a carbapenem. The emergence of the CTX-M enzyme makes
the treatment of infections arising in the community a problem

M ain risk factor associated with acquisition of multi-drug resistant A. baumannii (AbMR) strain was
imipenem monotherapy . AbMR strain caused septic shock in 16.6% of cases. It is also associated
with high rate of morbidity and mortality. High mortality rate and long hospital stay attributable to
infection and/or colonization with AbMR. Administration of imipenem and sulbactam combination,
colistin, or aminoglycoside eradicated strain in 30% of cases. Hypotension or septic shock around time
of isolation of bacterial strain a significant prognostic factor.

C ephalosporin use has been linked to subsequent infection with vancomycin-resistant enterococci
(VRE), extended-spectrum β-lactamase–producing Klebsiella pneumoniae, β -lactam–resistant
Acinetobacter species, and Clostridium difficile. The use of third-generation cephalosporins associated
with emergence of methicillin-resistant Staphylococcus aureus (MRSA), VRE, MDR Klebsiella,
Enterobacter, and MDR Acinetobacter. Quinolone use has been linked to infection with MRSA and with
increasing quinolone resistance in gram-negative bacilli, such as Pseudomonas aeruginosa. Use of
fluoroquinolones associated with emergence of MRSA, MDR Klebsiella, and MDR Pseudomonas and
Acinetobacter.

U se of carbapenems associated with emergence of MDR Klebsiella, Pseudomonas and Acinetobacter.

Increased carbapenem use may accelerate emergence of pan-resistant isolates. Neither 3rd
generation cephalosporins nor quinolones appear suitable for sustained use in hospitals as
“workhorse” antibiotic therapy. The use of 3rd generation cephalosporins and fluoroquinolones is
associated with the increased incidence of CDAD. The need for antibiotic stewardship is indisputable.
The need for new agents to treat nosocomial infections is critical. Imperative that substitution of either
broad-spectrum agents or combination therapy for the third-generation cephalosporins, fluoroquinolones, and
carbapenems be considered.

Keywords : “collateral damage”, drug-resistant, antibiotic, gram-negative bacteria