Antimicrobial Susceptibility of Gram-Negative Pathogens Isolated from Patients with Complicated Intra-Abdominal Infections in South African Hospitals (SMART Study 2004–2009): Impact of the New Carbapenem Breakpoints

Abstract

Background: The Study for Monitoring Antimicrobial Resistance Trends (SMART) follows trends in resistance among aerobic and facultative anaerobic gram-negative bacilli (GNB) isolated from complicated intra-abdominal infections (cIAIs) in patients around the world. Results: Enterobacteriaceae comprised 83.7% of the isolates. Escherichia coli was the species isolated most commonly (46.4%), and 7.6% of these were extended-spectrum b-lactamase (ESBL)-positive. The highest ESBL rate was documented for Klebsiella pneumoniae (41.2%). Overall, ertapenem was the antibiotic most active against susceptible species for which it has breakpoints (94.6%) followed by amikacin (91.9%), piperacillin-tazobactam (89.3%), and imipenem-cilastatin (87.1%), whereas rates of resistance to ceftriaxone, cefotaxime, ciprofloxacin, and levofloxacin were documented to be 29.7%, 28.7%, 22.5%, and 21.1%, respectively. Multi-drug resistance (MDR), defined as resistance to three or more antibiotic classes, was significantly more common in K. pneumoniae (27.9%) than in E. coli (4.9%; p < 0.0001) or Proteus mirabilis (4.1%; p < 0.05). Applying the new CLSI breakpoints for carbapenems, susceptibility to ertapenem was reduced significantly in ESBL-positive E. coli compared with ESBL-negative isolates (91% vs. 98%; p < 0.05), but this did not apply to imipenem-cilastatin (95% vs. 99%; p = 0.0928). A large disparity between imipenem-cilastatin and ertapenem susceptibility in P. mirabilis and Morganella morganii was documented (24% vs. 96% and 15% vs. 92%, respectively), as most isolates of these two species had imipenem-cilastatin minimum inhibitory concentrations in the 2-4 mcg/mL range, which is no longer regarded as susceptible. Conclusions: This study documented substantial resistance to standard antimicrobial therapy among GNB commonly isolated from cIAIs in South Africa. With the application of the new CLSI carbapenem breakpoints, discrepancies were noted between ertapenem and imipenem-cilastatin with regard to the changes in their individual susceptibilities. Longitudinal surveillance of susceptibility patterns is useful to guide recommendations for empiric antibiotic use in cIAIs.

The spread of carbapenem-resistant Enterobacteriaceae in South Africa: Risk factors for acquisition and prevention

“…For example, the ESBL rate for K. pneumoniae cultured from complicated intra-abdominal infections in private hospitals is 41.2% and that for bacteraemic isolates in the public sector 55 -74%. 7,8 These risk factors include: 3,9 • organ or stem cell transplantation • intensive care unit admission • poor functional status • severe illness • mechanical ventilation • prolonged hospitalisation • surgery.…”

National sentinel site surveillance for antimicrobial resistance in Klebsiella pneumoniae isolates in South Africa, 2010 - 2012

“…[2] There are few published reports on national antimicrobial resistance rates of K. pneumoniae in South Africa (SA), with data primarily emanating from the private sector, [3] regional studies with limited numbers of local isolates [1] or certain clinical settings. [4] To date, molecular data on ESBL K. pneumoniae in SA are based on detailed studies of small populations. Essack et al [5] examined bla SHV and bla TEM genes in 25 isolates, and found a high degree of diversity in terms of plasmids present, genes detected and the combination of genes within isolates.…”

Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials

“…However, as observed in a previous analysis of cIAI patients [27], the rates of clinical and bacteriological success achieved with moxifloxacin appear to be maintained well beyond the susceptibility breakpoint for key pathogenic species; this was observed during the long interval between 2000 and 2009 including each Phase III study period. Thus, despite recent warnings about the occurrence of resistant bacteria to major classes of antibiotics used to treat cIAIs that include not only fluoroquinolones but also carbapenems and piperacillintazobactam [29][30][31][32][33][34][35][36][37][38], our results may support the empiric use of antibiotics with a spectrum of activity covering the main causative organisms in cIAI patients with mild-to-moderate disease.…”