Antibiotic Resistance Patterns of Clinical Isolates of Serratia marcescens

Summary

  • Objective: Assess antibiotic resistance patterns of clinical Serratia marcescens isolates using disk diffusion and MIC (agar dilution).
  • Sample: 102 strains from three centers (62 MUSC, 22 Emory, 18 M. D. Anderson) collected June–December 1973.
  • Key result: Cephalothin resistance universal; ampicillin and tetracycline resistance very high; gentamicin, nalidixic acid, sulfisoxazole, and chloramphenicol most effective relatively.
  • Pigmented vs nonpigmented: pigmented strains show similar patterns with some higher resistance to certain drugs.
  • Implications: Resistance varies by hospital; R factors contribute transferable resistance; continuous surveillance recommended.

Methods

  • Disk sensitivity testing: standard single-disc method on Müller–Hinton agar using antibiotics: streptomycin (10 μg), sulfisoxazole (0.25 mg), tetracycline (30 μg), cephalothin (30 μg), kanamycin (30 μg), ampicillin (10 μg), nalidixic ext{ acid} (30 μg), gentamicin (10 μg), carbenicillin (50 μg), colistin (10 μg), tobramycin (10 μg), and chloramphenicol (30 μg).
  • MIC (agar dilution): using Steers inocula-replicating apparatus; inoculum ≈ 5\times 10^{4} bacteria; incubation 18\ {
    m h} at 37^{\circ}\text{C}; MIC = lowest concentration preventing visible growth.
  • Definitions: MIC determined for each drug; susceptibility patterns summarized across centers and in relation to pigmented status.

Results (disk sensitivity)

  • Cephalothin: 100\% resistant.
  • Ampicillin: 93\% resistant.
  • Tetracycline: 93\% resistant.
  • Colistin: 57\% resistant.
  • Carbenicillin: 39\% resistant.
  • Streptomycin: 34\% resistant.
  • Tobramycin: 26\% resistant.
  • Kanamycin: 22\% resistant.
  • Chloramphenicol: 16\% resistant.
  • Sulfisoxazole: 15\% resistant.
  • Gentamicin: 14\% resistant.
  • Nalidixic acid: 8\% resistant.
  • Multidrug resistance: 56/102 isolates resistant to ≥5 drugs; 14/102 resistant to ≥8; 5/102 resistant to all 12.
  • Center-specific patterns (disk tests):
    • M. D. Anderson: more frequently resistant to nearly all drugs except colistin and cephalothin.
    • Emory: more resistant to colistin, kanamycin, carbenicillin, sulfisoxazole, gentamicin, and streptomycin than MUSC.
    • MUSC: more susceptible overall than Emory to most drugs, except cephalothin, tobramycin, and chloramphenicol.

Results (pigmented vs nonpigmented)

  • Pigmented isolates: 11 strains; all pigmented resistant to cephalothin, ampicillin, and tetracycline.
  • All pigmented strains: susceptible to chloramphenicol, kanamycin, nalidixic ext{ acid}, sulfisoxazole, and gentamicin.
  • Pigmented strains also: 8/11 resistant to streptomycin, 8/11 resistant to colistin, 5/11 resistant to tobramycin.
  • Nonpigmented strains: 65% had MICs of streptomycin in the range 5-20\ \,\text{µg/mL} (most) versus pigmented strains showing higher MICs (20–40 \ µg/mL for streptomycin).

Results (MIC and pharmacodynamics)

  • Gentamicin, tobramycin, and chloramphenicol: >90\% inhibition at concentrations within therapeutically achievable serum levels.
  • Nalidixic acid: ≥90\% inhibition at concentrations achievable in urine.
  • Cephalothin and colistin: failed to inhibit isolates at achievable serum concentrations.
  • MICs for ampicillin, tetracycline, and cephalothin were higher in strains resistant to >5 drugs, indicating broader resistance.
  • Pigmented vs nonpigmented MIC trends largely similar except as noted for streptomycin.

Center-specific patterns (MIC interpretation)

  • Overall resistance pattern varied by center; patterns were characteristic for each hospital with respect to several drugs, except ampicillin, tetracycline, and cephalothin which remained universally or near-universally resistant across centers.
  • Implication: hospital-specific selective pressures influence resistance profiles.

Resistance mechanisms and implications

  • Reach of R factors: transferable resistance reported previously; present in multi-resistant strains in this study; ongoing work to characterize plasmids and their role in resistance augmentation.
  • Clinical implications: polymyxins and cephalosporins least effective in vitro; gentamicin, kanamycin, chloramphenicol, and nalidixic acid most effective in vitro; ampicillin, cephalothin, tetracycline, and colistin largely ineffective.
  • Public health note: resistance can vary over time and between hospitals; periodic surveillance is essential.

Summary takeaway

  • High-level: Serratia marcescens shows substantial multidrug resistance with hospital- and pigment-status-associated patterns; certain drugs (gentamicin, tobramycin, chloramphenicol, nalidixic acid) remain comparatively effective at achievable concentrations, while cephalothin and colistin are largely ineffective; ongoing surveillance and understanding of transferable resistance factors are crucial to guide therapy.