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Understanding antibiotic resistance
Understanding antibiotic resistance

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4 Case study: resistance to cephalosporins

In Week 3’s case study, you looked at the molecular mechanisms of resistance to cephalosporins and were introduced to ESBLs. The most common class of ESBLs in Europe is the CTX-M-type ESBL.

In this case study, you will explore how bacteria acquire resistance to cephalosporin antibiotics through horizontal gene transfer and the mutation of CTX-M-type ESBLs. You will begin by looking at how the presence of CTX-M-type ESBLs has changed in the UK over recent years.

Activity 5 The rise of CTX-M-type ESBLs

Timing: Allow about 20 minutes

The data in this activity are from The British Society for Antimicrobial Chemotherapy’s Resistance Surveillance Project (www.bsacsurv.org) which collects annual data on antibiotic resistance rates.

First, look at Figure 11 which shows the percentage of E. coli isolate producing CTX-M-type, or other, ESBLs between 2002 and 2016. Then answer the questions below.

Described image
Figure 11 BSAC UK bacteraemia susceptibility survey data for E. coli exhibiting an ESBL phenotype. Data from www.bsacsurv.org/ (accessed 13 November 2017).
Show description|Hide description

This figure comprises a bar graph showing the percentage of E. coli isolates exhibiting an ESBL phenotype in the UK between 2002 and 2016. The horizontal axis is labelled year and is marked from 2002 to 2016 in 1-year intervals, 2015 is missing. The vertical axis is labelled isolates (%) and is marked from 0 to 14 in intervals of 2. The blue bars represent CTX-M expressing E. coli isolates. The orange bars represent E. coli isolates expressing other ESBLs. In all cases except 2002 the blue bars are larger than the orange bars.

Figure 11 BSAC UK bacteraemia susceptibility survey data for E. coli exhibiting an ESBL phenotype. Data from www.bsacsurv.org/ (accessed ...

(a) Using the data in Figure 11, how has the proportion of isolates producing CTX-M-type ESBLs changed over time?

Discussion

The proportion of isolates producing CTX-M-type ESBLs was low in 2002 and increased to a peak in 2006. The percentage of resistant isolates decreased between 2007 and 2010 and then began to increase again, peaking in 2013.

(b) CTX-M-type ESBLs emerged in the late 1990s and were first reported in the UK in 2002. Suggest one possible reason for the change in frequency of these ESBLs in the UK over time.

Discussion

The increasing use of cephalosporin antibiotics could create conditions where resistance to cephalosporin antibiotics through the acquisition of CTX-M-type ESBLs is advantageous for the bacteria. Hence these conditions would satisfy Darwin’s conditions for evolution through natural selection.

(c) In Activity 7 in Week 1, you looked at how resistance to cephalosporins had changed in the UK over time (Figure 12). By comparing the data in Figures 11 and 12 do you think that the occurrence of CTX-M-type ESBLs is a good indicator of the rate of resistance to cephalosporins?

A bar graph showing resistance to cephalosporins in the UK between 2002 and 2015.
Figure 12 Resistance to cephalosporins in the UK between 2002 and 2015. Data from https://ecdc.europa.eu/en/antimicrobial-resistance/surveillance-and-disease-data/data-ecdc (accessed 13 November 2017).
Show description|Hide description

This figure comprises a bar graph showing resistance to cephalosporins in the UK between 2002 and 2015. The horizontal axis is labelled year and is marked from 2002 to 2015 in 1-year intervals. The vertical axis is labelled isolates resistant to 3rd gen. cephalosporins (%) and is marked from 0 to 16 in intervals of 2. The percentage increases steadily from approximately 2% in 2002 to approximately 15% in 2013 before decreasing to between 10 and 12% in 2014 and 2015.

Figure 12 Resistance to cephalosporins in the UK between 2002 and 2015. Data from https://ecdc.europa....

Discussion

Yes. Patterns of resistance to cephalosporins and the occurrence of CTX-M-type ESBLs were broadly similar between 2002 and 2016. This suggests that CTX-M occurrence is a good indicator of cephalosporin resistance and that the presence of CTX-M-type ESBLs in E. coli is the major cause of cephalosporin resistance.

(d) What challenges might these changes in the prevalence of CTX-M-type ESBLs present to health care?

Answer

The increasing frequency of cephalosporin-resistant bacteria and CTX-M-type ESBLs restricts the treatment options for infections caused by these bacteria.