Table 4 Examples of studies evaluating the emergence of antimicrobial resistance in response to antimicrobial exposure
Reference | Study | Key findings | ||||||
|---|---|---|---|---|---|---|---|---|
Typea | study population | drug of concern | bacterial target | endpoint or outcome relevant to antimicrobial resistance | controls | period of concernb | ||
Grade level: Controlled trial | ||||||||
[74] | SR of RCTs; n = 46 studies | pneumonia patients | imipenem | Pseudomonas aeruginosa | initial resistance; resistance emergence on treatment | other antimicrobials: beta-lactams, aminoglycosides, vancomycin, fluoroquinolone | 1993–2008 | resistance emerged: imipenem: 38.7% (range: 5.6–77.8%) of isolates comparator groups: 21.9% (range: 4.8–56.5%) |
[75] | MA of RCTs; n = 8 studies | patients with various infections | beta-lactam | various | emergence of antimicrobial resistance | other antimicrobials: beta-lactam and aminoglycoside combination | 1980–2004 | resistance emerged in various bacterial species (up to 20% of isolates); no significant difference between the two treatment arms in resistance emergence |
[85] | RCT; n = 313 patients | patients with nosocomial pneumonia, sepsis, or severe diffuse peritonitis | imipenem | Pseudomonas aeruginosa | emergence of antimicrobial resistance | imipenem plus netilmicin | 1988–1992 | resistance to imipenem occurred in monotherapy (n = 8) and combination therapy (n = 13) patients |
Grade level: Observational study | ||||||||
[76] | SR & MA of RCTs and OS; n = 24 studies | patients with various infections and healthy volunteers | various | various | resistance emergence under treatment | other antimicrobials | 1955–2009 | prescription of antibiotics in primary care is associated with resistance in bacteria |
[77] | cohort study; n = 271 patients | hospitalized patients with lab-confirmed Pseudomonas infection where initial isolate was susceptible | ceftazidime ciprofloxacin imipenem piperacillin | Pseudomonas aeruginosa | emergence of resistance during treatment | compare patients with resistance emergence to those without | 1994–1996 | resistance emerged in 10% of patients (n = 28); risk differed by antimicrobial drug |
[78] | cohort study; n = 2641 patients | coronary artery bypass graft surgery patients | Various; short vs. prolonged antibiotic prophylaxis | Enterobacteriaceae (cephalosporin resistant); Enterococci (vancomycin resistant) | emergence of resistance during prophylaxis | compare patients with acquired antibiotic resistance to those without | 1993–1997 | Prolonged antibiotic prophylaxis was associated with an increased risk of acquired antibiotic resistance |
[79] | CC study | patients with lab-confirmed bacteremia, resistant Pseudomonas | Piperacillin, ceftazidime, imipenem, ciprofloxacin, gentamicin, amikacin | Pseudomonas aeruginosa | odds of previous antibiotic treatment | patients with lab-confirmed bacteremia caused by susceptible Pseudomonas strains | 1989–1998 | previous exposure to antimicrobial monotherapy is associated with increased risk of subsequent resistance to that antimicrobial |
Grade level: Other | ||||||||
[80] | in vivo trial | mice experimentally challenged with bacteria | amikacin, ceftriaxone, perfloxacin or their combination | Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens | resistance emergence after treatment | other antimicrobials (single vs. combination therapy) | 1986 | resistance emerged in response to treatment; the frequency of resistance emergence varied by pathogen and antibiotic / combination |
[81] | in vitro trial (lab evolution system) | bacteria experimentally exposed to antimicrobial | colistin (different treatment regimen) | Acinetobacter baumannii | resistance emergence after exposure | negative control | 2007 | extensive resistance emerged during re-growth (as early as 6Â h after treatment) |
[82] | Cross-national database study (26 countries in Europe) | antibiotic use in outpatient settings (calculated as defined daily dose per 1000 inhabitants) and antibiotic resistance rates | various | various | correlation between antibiotic use and resistance across countries | n/a | 1997–2002 | rates of antibiotic resistance are higher in high consuming countries |