Detection and clinical significance of extended-spectrum beta-lactamases in a tertiary-care medical center

Abstract

The prevalence of extended-spectrum ␤-lactamase (ESBL)-mediated resistance remains unknown for most hospitals, and national guidelines for testing and reporting ESBL-mediated resistance have not yet been developed. We undertook a study to determine the prevalence of ESBLs and the clinical need for testing in our tertiary-care medical center. Members of the family Enterobacteriaceae isolated over a 6-month period for which ceftazidime or ceftriaxone MICs were greater than 1 g/ml were tested for production of ESBLs by the double-disk synergy method. Approximately 1.5% of isolates of the family Enterobacteriaceae (50 of 3,273), which were isolated from 1.2% of patients (23 of 1,844), were found to express ESBLs. ESBL-producing strains included eight different species and were isolated from patients located throughout the hospital, including outpatient clinics. By using the interpretive guidelines of the National Committee for Clinical Laboratory Standards, 26 to 39% of the isolates would have been reported to be susceptible to ceftazidime, depending upon the routine susceptibility method used. However, tests with cefpodoxime found all of the ESBL-producing strains to be resistant or intermediate. Nine patients infected with ESBL-producing isolates were treated with therapy which included an expanded-spectrum cephalosporin. Seven were cured. The deaths of the other two patients were not attributed to bacterial resistance missed by routine susceptibility testing. These observations suggest that in our tertiary-care medical center, it may not be clinically necessary or cost-effective at this time to institute additional testing on a routine basis to detect ESBL production in all clinical isolates of the family Enterobacteriaceae.

Therapeutic Challenges Associated with Extended‐Spectrum, β‐Lactamase‐Producing Escherichia coli and Klebsiella pneumoniae

“…No prospective studies were found regarding various treatment options and associated outcomes for serious infections due to ESBLproducing organisms. Limited data on treatment outcomes are available from seven case reports, [24][25][26][27][28][29][30] nine reports of nosocomial outbreaks [31][32][33][34][35][36][37][38][39] (which include brief descriptions of the subset of patients who required antimicrobial therapy), and two retrospective studies 40,41 (Table 1). Of note, most epidemiologic 40 Imp + Ak Ent, KP mostly Blood NS UNK 1 cured 1 34 Imp + Cp KP Blood, catheter-Imp ≤ 1.0 SHV-5 1 cured related Cp = NS 2 36 Imp + To KP Blood Imp = 0.12-1.0 UNK 2/2 cured To = 1-2 5…”

“…Imp KP Blood 4 cured, 1 died 17 35 25 CFT + Ak KP CSF, blood CFT ≤ 0.5-1.0 TEM-derived 1 cured 1 37 CFT Ent, mostly KP Septicemia CFT = 0.5-1.0 TEM-12, TEM-26 1 cured 1 27 CFT 2 g q6h KP Blood CFT = 0.75 (agar UNK 1 failed (cured with Cp disk diffusion) 400 mg q12h x 7 d) studies did not provide sufficient details on antibiotic regimen, dosage, and duration, or in vitro susceptibility of the agent. One retrospective study provided detailed information on antimicrobial therapy, particularly with extended-spectrum cephalosporins, 40 and 39 "Third-generation KP Urine NS TEM-10, TEM-26 2/2 cured cephalosporin" 4 32 CAX or CFT ± AG KP Urine CAX or CTX TEM-3-like, pI 6.3 4/4 cured = 0.5-4.0 (on selected isolates) 2…”

“…Mediastinitis, 2/2 relapsed 1 empyema 1 relapsed 3 37 CFT Ent, mostly KP NS CFT = 0.5-1.0 TEM-12, TEM-26 3/3 cured 1 36 P-T KP Blood P-T = 4-≥ 256 UNK 1 cured 1 26 P-T + Gm EC Blood, ascites P-T = 8 UNK, DDS(+) 1 died, septic shock Gm ≥ 256 1 40 Tim + Cp Ent, mostly KP Blood NS UNK, DDS(+) 1 cured 2 38 Ak KP Blood, urine NS UNK 2/2 cured 4 37 Ak Ent, mostly KP All sites includ-NS TEM-12, TEM-26 4/4 cured ing pneumonia, UTI, wound, peritonitis 2 36 To KP Blood To = 1.0-2.0 UNK, DDS(+) 1 cured, 1 died 1 27 Cp 400 mg q12h KP Blood, CVC Cp = 0.32 UNK, DDS(+) 1 cured x 7d 3 37 Cp Ent, mostly KP All sites NS TEM-12 or 3/3 cured (unspecified) TEM-26 (not specified) 1 40 Cp Ent, mostly KP Lungs NS UNK, DDS(+) 1 cured (pneumonia) 2 35 Cp + Gm or Ak KP All sites Cp = NS UNK, DDS(+) 2/2 cured (unspecified) Gm = 1-≥ 16 Ak = 4-16 1 40 T-S Ent, mostly KP Lungs NS UNK, DDS(+) 1 failed (pneumonia) 1…”

“…Among patients with blood stream infections, all three receiving ceftazidime monotherapy died, compared with 60% (3/5) mortality among those receiving combination therapy with ceftazidime and an aminoglycoside. 31,40,41 It is noteworthy that two patients with pneumonia and TEM-26-producing strains isolated from the oropharynx had resolution of pneumonia after ceftazidime monotherapy despite in vitro resistance. 31 The response in those two patients may be a reflection of difficulty correlating results of sputum cultures with clinical outcomes.…”

Evolution and epidemiology of extended-spectrum β-lactamases (ESBLs) and ESBL-producing microorganisms

“…However, because such drugs were often found to be non-efficacious in vivo [12][13][14][15][16], it is broadly accepted today that, aside from those identified in urinary tract infections, ESBL-producing isolates should, by definition, be reported as resistant to all ESBL substrates [4]. This creates a real challenge for clinical microbiology laboratories, which should precisely detect the ESBL phenotype [6,[17][18][19][20][21][22][23][24]. Finally, the third important aspect of the presence of ESBLs results from their complex and dynamic evolution and epidemiology.…”