Selected and Spontaneous Variants of <i>Serratia marcescens</i> with Combined Resistance against Chloramphenicol, Nalidixic Acid, and Trimethoprim

Abstract

Combined resistance against chloramphenicol (CHLOR), nalidixic acid (NA), and trimethoprim (TMP) was demonstrated in isolates and variants of a nosocomially significant, multiple-drug-resistant, nonconjugative strain of Serratia marcescens (bacteriocin type 18), either as a spontaneous event or after exposure of isolates and variants derived therefrom to increasing concentrations of CHLOR, NA, and TMP, respectively. This phenomenon was also noted among several selected mutants of two control strains of S. marcescens. The level of resistance was not absolute; the combined resistant mutants and variants were inhibited by 100–200 μg/ ml of CHLOR, 25–50 μg/ml of NA, and 12.5–25 μg/ml of TMP. However, the phenomenon of combined triple-resistance occurred irregularly with respect to the strain or variant of S. marcescens employed, and with regard to the selective drug utilized. Selection of mutants with CHLOR yielded a larger number of combined CHLOR-NA-TMP resistant mutants than selection with NA or TMP. Preliminary data obtained with spontaneously ‘cured’ variants of the multiple-drug-resistant strain of S. marcescens that had lost resistance against CHLOR, NA, TMP, penicillins, and aminoglycoside antibiotics, and which subsequently were shown to yield spontaneous mutants with combined triple-resistance against CHLOR, NA, and TMP, seem to indicate that this resistance phenomenon is not mediated extra-chromosomally, but rather chromosomally, and subject to phenotypic variation. The precise nature of this novel, unusual resistance mechanism against these three unrelated antimicrobial drugs remains to be elucidated.

Trimethoprim resistance

“…are intrinsically resistant to TMP because of poor penetration through the cell wall (35,82). Acquired TMP resistance based on cell wall permeability has been reported in Klebsiella pneumoniae and Serratia marcescens (74,86). Alterations in outer membrane proteins have been found associated with resistance to multiple antimicrobial agents, including TMP, in Klebsiella, Enterobacter, and Serratia isolates (34).…”

In vitro activity of A-56619 and A56620, two new aryl-fluoroquinolone antimicrobial agents

“…It has been reported previously that the quinolone carboxylic acid derivatives are relatively less active when tested against bacterial isolates with an underlying resistance to certain beta-lactams and amikacin (2,(4)(5)(6). Many of our gentamicin-resistant strains of Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens were also relatively or completely resistant to piperacillin and trimethoprim.…”

Outer Membrane Protein Alterations in <i>Serratia marcescens </i>Resistant against Aminoglycoside and β-Lactam Antibiotics

“…San ders and Watanakunakorn [9] presump tively characterized the OMP of variants of a strain of S. marcescens that resisted amikacin, cefotaxime, and ciprofloxacin; it was noted that two OMP (38 and 42 kd) were altered in these variants. How ever, nonspecific S. marcescens resistance against chloramphenicol, DNA gyrase in hibitors (nalidixic acid) and trimethoprim previously had been shown to be due to yet another mechanism [3,12,13]. In partic ular, Gutman et al [3] found that S. mar cescens variants resistant against this group of unrelated antimicrobial drugs re vealed one OMP alteration; a 40-kd pep tide was reduced significantly.…”