Antimicrobial activity of ceftazidime-avibactam and comparators against levofloxacin-resistant Escherichia coli collected from four geographic regions, 2012–2018

Distribution of levofloxacin-resistant E. coli isolates

A total of 10,840 isolates collected from four geographic regions and identified as resistant to levofloxacin were included in the analysis. Isolates were most commonly collected from UTIs (N = 3229; 29.8%), followed by 2564 (23.7%) from skin and skin structure infections, 2313 (21.3%) from intra-abdominal infections, 1482 (13.7%) from lower respiratory tract infections, and 1204 (11.1%) from bloodstream infections, whilst 48 (0.4%) were from an unknown or other source. A similar distribution was observed among ESBL-positive and ESBL-negative isolates (data not shown).

The highest proportion of isolates were collected from Europe (N = 4663; 43.0%). The proportion of isolates collected from Latin America (N = 2699; 24.9%) and Asia/South Pacific (N = 2337; 21.6%) were similar, and a minority were from Africa/Middle East (N = 1141; 10.5%).

Analysis of regions combined against levofloxacin-resistant E. coli

Table 1 shows the in vitro activity of ceftazidime-avibactam and comparators against levofloxacin-resistant ESBL-positive and ESBL-negative E. coli when data from all regions of collection were combined. Rates of susceptibility to ceftazidime-avibactam and colistin were similar (≥ 99.0%) in both sets of isolates. Other comparator agents with high susceptibility rates against both sets of isolates were meropenem and imipenem (≥ 98.5%), and tigecycline (≥ 94.6%). A high susceptibility rate was observed to amikacin among ESBL-negative isolates (95.1%); however, a lower rate of 83.4% was observed among ESBL-positive isolates. For cefepime, ceftazidime and aztreonam relatively high rates of susceptibility were observed among ESBL-negative isolates (≥ 88.5%); however, a susceptibility rate of < 10% was seen among ESBL-positive isolates.

Table 1 Activity of ceftazidime-avibactam and comparator agents against levofloxacin-resistant E. coli; ATLAS, 2012–2018Analysis by region against levofloxacin-resistant E. coli

For the regional analysis of all years pooled (2012–2018), presented in Table 2, susceptibility rates to ceftazidime-avibactam were consistently high in all regions for both ESBL-positive (97.0% in Asia/South Pacific to 99.7% in Africa/Middle East and Latin America) and ESBL-negative (99.4% in Asia/South Pacific to 100% in Latin America) levofloxacin-resistant E. coli. High susceptibility rates were also observed in each region among ESBL-positive and ESBL-negative isolates for colistin (≥ 98.5%), imipenem (≥ 96.5%), meropenem (≥ 96.5%) and tigecycline (≥ 94.1%).

Table 2 Activity of ceftazidime-avibactam and comparator agents against levofloxacin-resistant E. coli; ATLAS, by region, 2012–2018

Susceptibility rates to amikacin among ESBL-negative isolates were similar in all regions, from 94.4% in Africa/Middle East and Latin America to 96.5% in Europe. Among ESBL-positive isolates, susceptibility to amikacin was lower (79.9% in Europe to 89.8% in Asia/South Pacific). The susceptibility rates observed among ESBL-negative isolates to piperacillin-tazobactam were lowest in Europe (79.6%) and highest in Latin America (84.9%). In comparison, rates of susceptibility to piperacillin-tazobactam among ESBL-positive isolates were lower in each region, ranging from 61.1 to 74.0%.

High rates of susceptibility were observed among ESBL-negative levofloxacin-resistant E. coli for cefepime in all regions (between 91.1 and 93.3%) and for ceftazidime in three of the four regions (91.0 to 93.0%). A lower susceptibility rate to ceftazidime of 77.9% was observed among ESBL-negative isolates in Asia/South Pacific. Few ESBL-positive isolates from any region were susceptible to cefepime or ceftazidime (≤ 6.3%). Susceptibility rates to ampicillin and amoxicillin-clavulanate were lower compared with all other agents in each region for ESBL-negative isolates. Among each regional set of ESBL-positive isolates, susceptibility rates to ampicillin and amoxicillin-clavulanate were ≤ 41.6%.

In vitro activity data, by year, for ceftazidime-avibactam, colistin, meropenem, imipenem, and tigecycline against ESBL-positive and ESBL-negative isolates are presented in Additional file 1: Tables S1–S5. Over time, ceftazidime-avibactam, colistin, meropenem and imipenem showed consistently high and stable rates of susceptibility (≥ 96.7%) in Africa/Middle East, Europe and Latin America (Additional file 1: Tables S1–S4). For ESBL-positive isolates collected in the Asia/South Pacific region, reduced susceptibility rates were observed in 2018 to ceftazidime-avibactam (91.8%, Additional file 1: Table S1), and to imipenem (90.4%) and meropenem (91.1%) (Additional file 1: Tables S3 and S4) when compared with each of the preceding years. Susceptibility to tigecycline was > 92.6% between 2013 and 2018; rates of susceptibility were lower in 2012.

Regional trend tests against levofloxacin-resistant E. coli over time

Figure 1 shows the proportion of levofloxacin-resistant E. coli isolates identified as ESBL-positive from each region and by year. Any changes in the rates of ESBL-positive, levofloxacin-resistant E. coli over time were not statistically significant in Africa/Middle East and Latin America. For isolates from Europe and Asia/Pacific there was a statistically significant increase in the rates of ESBL-positive isolates over time (p = 0.0029 and p = 0.0001, respectively) with rates in 2018 of 54.4% in Europe and 61.3% in Asia–Pacific.

Fig. 1figure 1

Proportion of levofloxacin-resistant Escherichia coli isolates identified as ESBL-positive, 2012–2018. All regions: 2012, n = 487/1012; 2013, n = 792/1494; 2014, n = 844/1615; 2015, n = 718/1365; 2016, n = 901/1739; 2017, n = 887/1625; 2018, n = 1111/1990. Africa/Middle East: 2012, n = 39/86; 2013, n = 98/170; 2014, n = 109/204; 2015, n = 68/118; 2016, n = 77/157; 2017, n = 82/160; 2018, n = 136/246. Asia/South Pacific: 2012, n = 123/254; 2013, n = 148/291; 2014, n = 159/309; 2015, n = 152/271; 2016, n = 206/379; 2017, n = 204/358; 2018, n = 291/475. Europe: 2012, n = 175/422; 2013, n = 361/701; 2014, n = 347/727; 2015, n = 305/620; 2016, n = 316/709; 2017, n = 343/669; 2018, n = 443/815. Latin America: 2012, n = 150/250; 2013, 185/332; 2014, n = 229/375; 2015, n = 193/356; 2016, n = 311/494; 2017, n = 258/438; 2018, n = 241/454

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