Ciprofloxacin-Resistant E. coli in UTIs
Ciprofloxacin-resistant E. coli in urinary tract infections is primarily associated with ESBL-producing strains, strains with plasmid-mediated quinolone resistance genes (qnrA, qnrB, aac(6')-1b-cr), and strains with specific chromosomal mutations in DNA gyrase genes.
Genetic Mechanisms of Resistance
The molecular basis of ciprofloxacin resistance in E. coli involves multiple mechanisms that often coexist:
ESBL-producing E. coli (particularly CTX-M-15 type) are strongly associated with fluoroquinolone resistance, with 12 of 17 fluoroquinolone-resistant E. coli isolates in one study producing plasmid-mediated CTX-M-15 ESBLs 1
Plasmid-mediated quinolone resistance occurs through qnrA and qnrB genes, as well as the ciprofloxacin-acetylating enzyme aac(6')-1b-cr 1
Chromosomal mutations in DNA gyrase genes cause amino acid substitutions at positions 83 (Serine to Leucine) and 87 (Aspartic acid to Asparagine), which confer high-level resistance (MIC >32 μg/mL for both levofloxacin and ciprofloxacin) 1
Resistance typically results from a combination of these mechanisms rather than a single mutation, making these strains highly resistant 1
Clinical Risk Factors for Resistant Strains
Several patient and exposure factors predict ciprofloxacin-resistant E. coli UTIs:
Previous fluoroquinolone use is the strongest modifiable risk factor, with two prescriptions conferring an odds ratio of 5.89 (95% CI 3.45-10.03) and three or more prescriptions an OR of 3.38 (95% CI 1.92-5.97) 2
Complicated UTIs have significantly higher resistance rates (38% vs 17% in uncomplicated UTIs, OR 2.4,95% CI 1.54-3.61) 3
Advanced age (>50 years or >65 years) independently increases risk (OR 1.6 for age >50; OR 6.48 for age ≥65) 3, 4
Urological abnormalities carry the highest risk (OR 7.98,95% CI 2.7 to 3.1) 4
Urinary catheterization increases risk (OR 2.92,95% CI 1.1 to 8.5) 4
Relapsing infections are more common with resistant strains (22% vs 0% in susceptible strains) 4
Geographic and Temporal Trends
Resistance rates vary significantly by region and have increased dramatically over time:
Spain shows the highest resistance at 31% (increased from 15% in 2000) 5
Germany has 21% resistance (increased from 2% in 2000) 5
United Kingdom has 15% resistance (increased from 1% in 2000 and 2008) 5
Sweden has 7-15% resistance (increased from 0% in 2000) 5
Turkey reports 17% resistance in uncomplicated UTIs and 38% in complicated UTIs 3
Important Clinical Caveats
ESBL co-resistance: Detection of ESBL-producing strains is twice as common in patients who received ciprofloxacin compared to those who did not (15% vs 7.4%), indicating cross-selection pressure 3
Asymptomatic bacteriuria: Patients with ciprofloxacin-resistant strains more frequently present with asymptomatic bacteriuria or lower urinary tract symptoms (85% vs 61%) rather than severe pyelonephritis 4
Community acquisition: These resistant strains are increasingly community-acquired rather than healthcare-associated, with clonally-related strain types circulating in communities 1
The FDA label confirms that many Enterococcus faecalis strains are only moderately susceptible to ciprofloxacin, and resistance develops slowly through multiple step mutations 6