Quantifying the associations between antibiotic exposure and resistance - a step towards personalised antibiograms

Abstract

Empirical antibiotic treatment is selected to target causative bacteria with antibiotics to which they are not resistant. We analysed the increase in bacterial resistance among individual patients associated with antibiotic exposure in the month prior to infection onset, compared to unexposed patients. From a series of prospective cohort studies in the period 2002-2011 at Beilinson Hospital, Israel, 4232 consecutive patients suspected of infection were included. We analysed resistance to antibiotics in bacterial isolates from patients with clinically significant and microbiologically documented infections, starting antibiotics after obtaining cultures (n = 775). In Gram-negative bacteria, significantly higher rates of resistance was associated with exposure to antibiotics, while no significant associations were found for Gram-positive bacteria. Significant odds ratios (ORs) for increased resistance to classes of antibiotics ranged from 2.1 to 3.3 in Gram-negative bacteria from patients exposed to any antibiotic(s), with quinolones having the highest OR, followed by aminoglycosides, penicillins with β-lactamase inhibitor and cephalosporins. The majority of significant associations also had significant ORs after exposure to another class of antibiotics, indicating a substantial effect of cross-resistance. In conclusion, increased resistance was observed following exposure to antibiotics, both from the same class and from other classes. The results indicate a reason to adjust the expected coverage of empirical antibiotic treatments for patients recently exposed to antibiotics, with some antibiotics being more affected than others.

Characterization of Biological Resistance and Successful Drug Resistance Control in Medicine

“…The other complication which arises as part of this worsening of resistance is that, as more and more molecules become resisted as a result of our continued supply of newer and newer molecules to pathogens, there is going to also be a parallel and continued increase in the number of resisted but not-yet-created molecules due to entrained resistance [12], entrained resistance being favored by resisted molecules leading resistant pathogens to exhibiting cross-resistance to other molecules of the same class or to other molecules of totally different classes [90]. So, we will not only be dealing with known resisted molecules; we will also be dealing with resisted but not-yet-created molecules.…”

Risk Factors and Outcomes of Multidrug-Resistant Bacteria Infection in Infected Pancreatic Necrosis Patients

“… 31 Patients need multiple surgical interventions, which are more prone to postoperative complications, resulting in prolonged hospital stay and increased mortality. 32 , 33 3) With the expansion of pancreatic necrosis, it is suggested that patients have more pancreatic acinar cell damage, and a large amount of inflammatory factors into the blood, causing SIRS, clinicians have the possibility of prophylactic application of antibiotics due to the suspicion of patient infection, which prone to develop MDRB infection. 8 , 32 , 34 Therefore, for patients with suspected infection, clinicians should base their treatment strategy on the time of symptom onset, the latest imaging findings, changes in clinical symptoms (cough, sudden or persistent high fever, etc.…”

“… 32 , 33 3) With the expansion of pancreatic necrosis, it is suggested that patients have more pancreatic acinar cell damage, and a large amount of inflammatory factors into the blood, causing SIRS, clinicians have the possibility of prophylactic application of antibiotics due to the suspicion of patient infection, which prone to develop MDRB infection. 8 , 32 , 34 Therefore, for patients with suspected infection, clinicians should base their treatment strategy on the time of symptom onset, the latest imaging findings, changes in clinical symptoms (cough, sudden or persistent high fever, etc. ), and whether different treatment modalities have been performed (placement of deep venous catheters or indwelling urinary catheters, etc.)…”

Bystander Selection for Antimicrobial Resistance: Implications for Patient Health

“…These studies did not report the target of prior antimicrobial therapy; however, most included only the first occurrence of infection with the focal pathogen [ 81 – 85 ], implying that off-target exposure ( Figure 3 , pathway B) contributes to increased risk for carbapenem-resistant nosocomial infections. Similar studies found that prior antimicrobial use elevates risk for vancomycin resistance in enterococcal infections [ 89 ], methicillin resistance in nosocomial S. aureus infections [ 90 ], colistin resistance in bloodstream K. pneumoniae infections [ 91 ], carbapenem resistance in P. aeruginosa [ 92 ], resistance in invasive pneumococcal disease [ 93 ], and resistance in infections caused by Gram-negative bacteria [ 94 ].…”