Activity Of Ertapenem Research Articles

Radiosynthesis, quality control, biodistribution, and infection-imaging study of a new 99mTc-labeled ertapenem radiopharmaceutical.

Ertapenem is a member of carbapenem antibiotics used for the treatment of moderate-to-severe intra-abdominal, urinary tract, acute pelvic, and post-surgical gynecologic infections. The antibacterial activity of ertapenem is mediated through binding to penicillin-binding proteins which results in inhibiting the cross-linking of the peptidoglycan layer of the bacterial cell wall. Therefore, ertapenem can be labeled with technetium-99m (99mTc), a gamma emitter radionuclide, for the diagnosis of deep-seated bacterial infections, such as urinary tract, intra-abdominal, osteomyelitis, and post-surgical gynecologic infections. The labeling procedure was carried out by varying the reaction conditions, such as the amount of the ligand and reducing agent, pH, reaction time and temperature, and radioactivity. At optimized reaction conditions more than 93% 99mTc-ertapenem radioconjugate was obtained. 99mTc-ertapenem was found 90% intact in saline medium up to 6 h, while 88% intact in human blood serum up to 3h. Biodistribution study showed target-to-non-target ratios of 2.91 ± 0.19, 2.39 ± 0.31, and 1.23 ± 0.22 in S. aureus, E. coli, and turpentine oil-infected rat models, respectively. The SPECT scintigraphy showed high uptake of 99mTc-ertapenem in bacterial-infected abscesses, and low counts were recorded in normal and turpentine oil-inflamed tissues. In conclusion, 99mTc-ertapenem can be a potent infection-imaging agent, which can diagnosis deep-seated bacterial infections at early stage but need further pre-clinical evaluation in variety of infection models.

In Vitro Activity of Ertapenem against Neisseria gonorrhoeae Clinical Isolates with Decreased Susceptibility or Resistance to Extended-Spectrum Cephalosporins in Nanjing, China (2013 to 2019).

ABSTRACTNeisseria gonorrhoeae isolates collected in Nanjing, China, that possessed decreased susceptibility (or resistance) to extended-spectrum cephalosporins (ESCs) were examined for susceptibility to ertapenem, and their sequence types were determined. Ceftriaxone and cefixime MICs of ≥0.125 mg/L and ≥0.25 mg/L, respectively, were first determined in 259 strains isolated between 2013 and 2019, and then MICs of ertapenem were measured using the antimicrobial gradient Epsilometer test (Etest). Also, genetic determinants of ESC resistance were identified and N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed to analyze associations with ertapenem susceptibility. All isolates displayed ertapenem MICs between 0.006 mg/L and 0.38 mg/L; the overall MIC50 and MIC90 were 0.032 mg/L and 0.125 mg/L, respectively. Forty-four (17.0%) isolates displayed ertapenem MICs of ≥0.125 mg/L; 10 (3.9%) had MICs of ≥0.25 mg/L. The proportion of isolates with ertapenem MICs of ≥0.125 mg/L increased from 4.0% in 2013 to 20.0% in 2019 (χ2 = 24.144, P < 0.001; chi-square test for linear trend). The penA mosaic allele was present in a significantly higher proportion of isolates with ertapenem MICs of ≥0.125 mg/L than of isolates with MICs of ≤0.094 mg/L) (97.7% versus 34.9%, respectively; χ2 = 58.158, P < 0.001). ST5308 was the most prevalent NG-MAST type (8.5%); ST5308 was also significantly more common among isolates with ertapenem MICs of ≥0.125 mg/L than isolates with MICs of ≤0.094 mg/L (22.7% and 5.6%, respectively; χ2 = 13.815, P = 0.001). Ertapenem may be effective therapy for gonococcal isolates with decreased susceptibility or resistance to ESCs and isolates with identifiable genetic resistance determinants.

Potent Activity of Ertapenem Plus Cefazolin Within Staphylococcal Biofilms: A Contributing Factor in the Treatment of Methicillin-Susceptible Staphylococcus aureus Endocarditis.

BackgroundBesides antistaphylococcal beta-lactams and source control, there are limited validated antimicrobial salvage options in patients with prolonged methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including infective endocarditis (IE).MethodsMSSA IE cases treated with ertapenem (ETP) plus cefazolin (CZ) were compared with matched IE cases treated with standard beta-lactam monotherapy. The bactericidal activity of ETP plus CZ was also compared with nafcillin (NAF), CZ, and ETP alone using an in vitro MSSA biofilm model.ResultsThe median duration of bacteremia experienced by patients (n = 12) while on CZ or NAF was 4 days (range 1–16 days) compared with 1 day (range 1–3 days) for patients (n = 5) treated with ETP + CZ (P = .01, Mann-Whitney U test). Cefazolin and NAF alone or in combination did not achieve biofilm eradication at clinically relevant concentrations. However, the addition of ETP to CZ led to bactericidal eradication within biofilms at standard dosing.ConclusionsErtapenem reduces CZ concentrations required to eradicate MSSA biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis. Larger studies are needed to investigate ETP plus CZ therapy in the treatment of biofilm-related MSSA infections such as endocarditis.

Ertapenem and Faropenem against Mycobacterium tuberculosis: in vitro testing and comparison by macro and microdilution

BackgroundInterest in carbapenems has been rising in the last few years due to the emergence of drug resistant tuberculosis. Ertapenem (ETP), given once a day parenteral, and faropenem (FAR), oral, have a better administration profile than meropenem (MEM), imipenem (IPM) and doripenem (DOR). The addition of amoxicillin-clavulanate (AMC) inhibits the hydrolysis by the carbapenemase present in Mycobacterium tuberculosis (MTB).The aim of this study was to determine the in vitro activity of ETP and FAR against susceptible and resistant clinical MTB strains by two widely use methodologies, the BACTEC960 MGIT and microdilution.Results19 clinical isolates with different susceptibility profiles and H37Rv were included. Minimal inhibitory concentration (MIC) testing was performed using two methods of different concentrations of ETP and FAR with and without AMC.MIC50 was 2 and 8 for FAR with and without AMC by both methods. MIC90 was > 16 and > 8 by microdilution and MGIT respectively and did not change after AMC addition.18/20 samples were resistant to the highest concentration of ETP, with and without AMC. Half of the samples had some susceptibility to FAR; addition of AMC further reduced the MIC level in seven isolates.10/20 isolates showed susceptibility to FAR and the addition of AMC further reduced the MIC in 7 isolates. However, most of the MICs were near the limit of effectiveness (8 μg/mL).Resistance to FAR was associated with resistance to MEM (p = 0.04) but not to resistance profiles of other drugs, including M/XDR status.ConclusionsThe lack of ETP activity may be associated with its degradation, independent of carbapenemase, during incubation.No susceptibility pattern to traditional drugs can predict susceptibility to FAR and susceptibility testing is not routinely available. PK/PD studies are needed as reaching the concentrations tested in these experiments may be challenging.This work highlighted some of the limitations of carbapenem use. More evidence is needed to clarify their true impact in TB treatment and outcome, considering the financial burden, complications and microbiota changes associated with their use.

The Radiation Sterilization of Ertapenem Sodium in the Solid State.

For the first time, the influence of ionising radiation on the physicochemical properties of ertapenem in solid state was studied. During our studies, we evaluated the possibility of applying radiosterilization to obtain sterile ertapenem. Spectroscopic (Fourier Transform Infrared (FT-IR)), thermal (differential scanning calorimetry (DSC), chromatography (High-Performance Liquid Chromatography (HPLC) and HPLC-MS), and X-ray powder diffraction (XRPD) studies shown that irradiation of ertapenem with the 25 kGy, the dose required to achieve sterility, does not change the physicochemical properties of the studied compound. The antimicrobial activity of ertapenem irradiated with the dose of 25 kGy was only reduced for one species. Based on the received results, we can conclude that radiostelization is a promising alternative method of obtaining sterile ertapenem. In our studies, ertapenem was also exposed to e-beam radiation with a dose of 400 kGy. It was determined that two novel degradation products that are structurally differently to degradants formed during hydrolysis and thermolysis.

Monitoring the antimicrobial susceptibility of Gram-negative organisms involved in intraabdominal and urinary tract infections recovered during the SMART study (Spain, 2016 and 2017).

Continuous antimicrobial resistance surveillance is recommended by Public Health authorities. We up-dated data from the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain. The antimicrobial susceptibility data and extended-spectrum beta-lactamase (ESBL) production in isolates recovered from intra-abdominal (IAI) (n=1,429) and urinary tract (UTI) (n=937) infections during the 2016- 2017 SMART study in 10 Spanish hospitals were analysed. Escherichia coli was the most frequently microorganism isolated (48.3% and 53.7%) followed by Klebsiella spp. (11.5% and 21.9%) in IAIs and UTIs, respectively. Figures for Pseudomonas aeruginosa were 9.0% and 6.1%, being more frequently recovered from patients with nosocomial infections. Overall, 9.9% (IAI) and 14.0% (UTI) of E. coli, Klebsiella spp. and Proteus mirabilis isolates were ESBL-producers, being Klebsiella pneumoniae (34.5%) from UTI of nosocomial origin the most frequent. ESBL-producers were higher in patients >60 years in both IAIs and UTIs. As in previous years, amikacin (96.3%-100% susceptibility), ertapenem (84.2%-100%) and imipenem (70.3%- 100%) were the most active antimicrobials tested among Enterobacterales species. The activity of amoxicillin-clavulanic, piperacillin-tazobactam, and ciprofloxacin susceptibility was lower, particularly among ESBL-producers. Ertapenem susceptibility (88.9%-100%) was retained in ESBL-E. coli isolates that were resistant to these antimicrobials but decreased (28.6%-100%) in similar isolates of K. pneumoniae. Continuous antimicrobial resistance surveillance from the SMART study reveals overall maintenance of ESBL-producers in Spain, although with higher presence in isolates from UTIs than from IAIs. Moreover, ertapenem activity was high in E. coli irrespective of ESBL production but decreased in K. pneumoniae, particularly among ESBL-producers.

2447. Ertapenem and Faropenem for the Treatment of Drug-Resistant Tuberculosis

BackgroundCarbapenems are a class of β-lactam antibiotics which include imipenem, meropenem and ertapenem. More recently, a new oral carbapenem (faropenem) have been marketed in a limited number of countries (in particular, India and Japan). Emerging evidence demonstrates that they target the mycobacterial cell wall, providing an alternative treatment for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), where options are limited. Compared with imipenem and meropenem (both only available as intravenous formulations), ertapenem (once daily administration) and faropenem (oral) are much more attractive alternatives for ambulatory or homecare treatment. However, there is a paucity of data on their efficacy against M. tuberculosis. The aim of this project was to test the in vitro activity of ertapenem and faropenem (with and without the addition of amoxicillin/clavulanate) against different clinical isolates of M. tuberculosis and the reference strain H37RV, to better understand their potential role as additional antibiotics in the management of drug-resistant TB.MethodsTwenty isolates in total (19 clinical isolates, including MDR and XDR strains, plus H37Rv) were tested against different concentrations of ertapenem and faropenem (with and without the addition of amoxicillin/clavulanate). Susceptibility testing was performed using two different methods (BACTEC960 and broth microdilution). A degradation assay was also performed to evaluate the stability of ertapenem.ResultsEighteen out of 20 samples were resistant to the highest concentration of ertapenem tested (including the addition of amoxicillin/clavulanate). Half of the samples tested showed some degree of susceptibility to faropenem and the addition of amoxicillin/clavulanate further reduced the MIC level in seven isolates.ConclusionThe results from this project have highlighted a significant level of in vitro resistance to ertapenem, whilst the clinical isolates have shown different degrees of susceptibility to faropenem. Although promising agents (in particular, faropenem), carbapenems will remain a third line choice to be used only in cases of XDR TB. There is currently no evidence to prefer the use of ertapenem despite its once daily administration.Disclosures All authors: No reported disclosures.

Activity of Ertapenem against Enterobacteriaceae in seven global regions-SMART 2012-2016.

Antimicrobial resistance among Enterobacteriaceae has been increasing globally especially due to extended-spectrum-β-lactamases (ESBLs), which typically necessitate the use of carbapenems for treatment of serious infections. Emerging carbapenem-resistant Enterobacteriaceae further complicate therapy. As part of the Study for Monitoring Antimicrobial Resistance Trends (SMART), this analysis examined the recent activity of a key carbapenem (ertapenem) and other important therapeutic options against Enterobacteriaceae. From 2012 to 2016, 224 hospitals in 57 countries collected up to 100 consecutive gram-negative bacilli from intra-abdominal (IAI) and 50 from urinary tract infections (UTI) per year, totaling 106,300 Enterobacteriaceae isolates. Susceptibility was determined using CLSI broth microdilution and breakpoints. Although statistically significant decreasing trends in ertapenem activity against Enterobacteriaceae were found in all regions except Middle East, the actual size of the decreases was < 3 percentage points, and susceptibility in 2015-2016 remained ca. 90% or higher, ranging from 89.5% in Asia to 97.3% in US/Canada. Of the comparators, only amikacin exceeded these results. Ertapenem was active against > 90% of isolates with ESBL phenotype from Latin America, Middle East, South Pacific, and US/Canada, and against > 80% of MDR isolates in all regions except Africa (72.9%), Asia (75.1%), and Europe (78.0%). Only imipenem, amikacin, and colistin exceeded these rates. Ertapenem, which is popular among clinicians due to its convenient once-daily dosing schedule and favorable safety and tolerability profile, remains highly active against Enterobacteriaceae from IAI and UTI, even as ESBLs and other resistance mechanisms limit therapeutic options, but continued susceptibility testing for surveillance and individual patients is important.

The Plasma Protein Binding Proteome of Ertapenem: A Novel Compound-Centric Proteomic Approach for Elucidating Drug–Plasma Protein Binding Interactions

Ertapenem is an important first-line carbapenem antibiotic used for the treatment of aerobic Gram-negative bacterial infections. It is the only marketed carbapenem that is highly bound to plasma proteins and displays a concentration-dependent and saturable plasma protein binding profile. To date, the plasma components responsible for sequestering ertapenems antibacterial activity remain uncharacterized. In the present study, we have employed an orthogonal, multiplatform approach, including novel compound-centric displacement proteomics and surface plasmon resonance to characterize the plasma protein binding proteome of ertapenem. In proof-of-concept, the capacity of physiological cocktails of the identified plasma proteins to inhibit the antibacterial activity of ertapenem was assessed with in vitro microbiological assays. We show that fibrinogen, complement C4, haptoglobulin, α-1-antitrypsin, fibronectin, transferrin, immunoglobulin G, hemopexin, and humans serum albumin are responsible for the majority of the sequestering activity in plasma. No binding was observed to α-1-acid-glycoprotein. The findings of this study have broad reaching implications for antibiotic drug design and for dose tailoring to suit the plasma protein levels of individual patients in order to maximize the clinical efficacy of important first-line antibiotics such as ertapenem.

Pharmacodynamic activity of ertapenem versus genotypically characterized extended-spectrum β-lactamase (ESBL)-, KPC- or NDM-producing Escherichia coli with reduced susceptibility or resistance to ertapenem using an in vitro model.

We assessed the pharmacodynamic activity of ertapenem against Escherichia coli with reduced susceptibility (MIC 0.12-0.5 mg/L), intermediate resistance (MIC 1.0 mg/L) or resistance (MIC ≥ 2 mg/L) to ertapenem using an in vitro model. Fifteen extended-spectrum β-lactamase- or carbapenemase-producing E. coli were studied. The in vitro pharmacodynamic model was inoculated with ∼1 × 10(6) cfu/mL and ertapenem was dosed once daily at 0 and 24 h to simulate free (ƒ) Cmax and t½ obtained after either 1 g or 2 g intravenous once-daily doses in healthy volunteers (1 g: ƒCmax 15 mg/L, t½ 4 h). Sampling was performed over 48 h to assess viable growth and resistance selection. An ertapenem T> MIC ≥ 75.4% (ertapenem MICs ≤ 0.5 mg/L) resulted in bactericidal (≥ 3 log10 killing) activity against all strains. An ertapenem T>MIC of 61% was bactericidal at 6 and 12 h but regrowth at 24 and 48 h occurred in some strains. An ertapenem T>MIC of 13%-43% was bactericidal at 6 h but regrowth (with MIC increases) occurred. No inhibition of an NDM strain with an ertapenem T>MIC of 0% (ertapenem MIC 256 mg/L) occurred at any timepoint. Once-daily dosing with 1 g of ertapenem was bactericidal against ESBL-producing E. coli with ertapenem MICs ≤ 0.5 mg/L and was bactericidal against strains with MICs of 1.0 mg/L, with regrowth in some strains. Ertapenem MICs of 2-8 mg/L resulted in early bactericidal activity followed by regrowth. Once-daily dosing with 2 g of ertapenem was bactericidal against strains with an MIC of 1.0 mg/L, but regrowth occurred in some strains with an ertapenem MIC of 2 mg/L.

Evaluation of the activity of ertapenem against gonococcal isolates exhibiting a range of susceptibilities to cefixime

There is a need for new or alternative antimicrobial agents for the treatment of gonorrhoea as antimicrobial resistance emerges to current therapies. The aim was to investigate the activity of ertapenem against isolates of Neisseria gonorrhoeae with decreased susceptibility to cefixime. A panel of 52 clinical isolates and 10 control strains of N. gonorrhoeae were selected to represent a range of susceptibilities to cefixime. Susceptibility testing was performed using the methodology used for the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). The isolates were typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST). The isolates comprised 42 different molecular types as defined by NG-MAST. The susceptibility of the clinical isolates to ertapenem was similar to that of cefixime, with a Pearson's correlation coefficient of R = 0.89. The MIC90 and MIC50 values of ertapenem were 0.25 and 0.12 mg/L, respectively, while those of cefixime were 0.12 and 0.06 mg/L, respectively. However, these isolates were more susceptible to ceftriaxone than ertapenem, with a Pearson's correlation coefficient of R = 0.65 and ceftriaxone MIC90 and MIC50 values of 0.03 and 0.016 mg/L, respectively. The isolates that were least susceptible to ertapenem were all non-producers of penicillinase. However, one isolate that was highly resistant to cefixime and ceftriaxone was more susceptible to ertapenem than either cefixime or ceftriaxone. This study has shown that ertapenem is not a suitable alternative for first-line treatment for gonorrhoea but that it may be useful for the treatment of highly resistant infections.

Etiology, Extended-spectrum β-lactamase Rates and Antimicrobial Susceptibility of Gram-negative Bacilli Causing Intra-abdominal Infections in Patients in General Pediatric and Pediatric Intensive Care Units—Global Data From The Study for Monitoring Antimicrobial Resistance Trends 2008 to 2010

Antimicrobial resistance has been increasing for several years and is often higher in intensive care units (ICUs) than in other facilities. The spread of extended-spectrum β-lactamases (ESBLs) in particular has profoundly impacted antimicrobial efficacy and usage. The Study for Monitoring Antimicrobial Resistance Trends has monitored the in vitro activity of ertapenem and several comparators against aerobic gram-negative bacteria from intra-abdominal infections (IAIs) for many years. This report summarizes susceptibility levels and epidemiology for key IAI pathogens cultured from general pediatric medical wards and pediatric ICUs globally. 1248 gram-negative bacteria were collected from pediatric IAIs by 113 labs in 40 countries from 2008 to 2010. Susceptibility was determined by Clinical and Laboratory Standards Institute broth microdilution. Susceptibility rates (%S) were determined for species with ≥10 isolates. Sixty-two percent of isolates came from general pediatric wards and 38% from pediatric ICUs. The overall ESBL-positive rate was 11.0% for Escherichia coli and 38.9% for Klebsiella pneumoniae; the ESBL-positive rate for E. coli was twice as high in ICU as non-ICU. Most study drugs inhibited >90% of ESBL-negative isolates, but only the carbapenems inhibited >90% of ESBL-positive E. coli and only imipenem inhibited >90% of ESBL-positive K. pneumoniae. Amikacin, imipenem and ertapenem were the most active against gram-negative bacteria from pediatric IAIs, followed closely by the fluoroquinolones and cefepime. Other cephalosporins were often <90% active. ESBL rates were 38.9% for K. pneumoniae and 11.0% for E. coli. Therapy for pediatric IAIs should take into consideration local ESBL rates because only carbapenems inhibited most of these pathogens.

Epidemiology and Susceptibility of Gram-Negative Appendicitis Pathogens: SMART 2008–2010

The Study for Monitoring Antimicrobial Resistance Trends (SMART) has tracked the in vitro activity of ertapenem and comparators against aerobic gram-negative bacteria from intra-abdominal infections since 2002. This report describes the epidemiology and susceptibility for clinical isolates associated with appendicitis, collected from 2008 to 2010. A total of 1,720 gram-negative bacilli were collected from patients with appendicitis in 122 hospitals in 39 countries worldwide; of these, 23% of isolates were from pediatric patients (≤ 17 years old). Minimum inhibitory concentrations (MICs) and extended-spectrum β-lactamase (ESBL) phenotypes were determined by broth microdilution and interpreted using Clinical and Laboratory Standards Institute guidelines. The global ESBL-positive rate was 16.3%, ranging from 2.2% for Proteus mirabilis to 16.6% for Escherichia coli and 20.1% for Klebsiella pneumoniae. The ESBL-positive rates differed by age group (17.7% in adults vs. 11.4% in children) and by geographic region, with significantly higher rates in Asia/Pacific (28.0%) and significantly lower rates in North America (9.1%), Africa/Middle East (4.8%), and Europe (4.4%). Amikacin, imipenem-cilastatin, piperacillin-tazobactam, and ertapenem were the most active of the tested agents against aerobic gram-negative appendicitis pathogens across pediatric and adult age groups and across geographic regions, including ESBL-positive isolates. Cefepime and ceftazidime were active against ≥ 90% of global pediatric isolates. E. coli, by far the most frequently isolated species (68% in adults and 75% in pediatric patients), was significantly less susceptible in adults than in pediatric patients (p<0.05; Fisher exact test) to all tested agents except amikacin, ertapenem, imipenem-cilastatin, piperacillin-tazobactam, and ampicillin-sulbactam (with the latter showing low activity in both age groups). These in vitro data suggest that amikacin, imipenem-cilastatin, piperacillin-tazobactam, and ertapenem would perform well against aerobic gram-negative bacilli associated with appendicitis in both adults and children, especially in regions with high rates of ESBL-positive E. coli.

Monitoring the global in vitro activity of ertapenem against Escherichia coli from intra-abdominal infections: SMART 2002–2010

During 2002–2010, a total of 30840 Escherichia coli clinical isolates from intra-abdominal infections were collected globally in the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance programme. The incidence of extended-spectrum β-lactamase (ESBL)-producing isolates ranged from 9.2% in 2002 to 21.2% in 2010. The highest rates were observed in Asia (38.3%) and Latin America (22.9%) and the lowest rates in Africa (6.3%), North America (6%) and South Pacific (5.8%). Global susceptibility trends showed that there were only minor fluctuations in susceptibility to ertapenem and imipenem, with no significant decrease over time. Against ESBL-positive isolates, ertapenem susceptibility significantly increased during 2002–2010 globally. Moreover, susceptibility to ertapenem in the different geographical regions studied was also high, with only minor fluctuations generally observed. Notably, in Asia where the highest ESBL-positives rates (38.3%) were observed, susceptibility to ertapenem had actually significantly increased in this population during the 9-year study period. By contrast, susceptibility to amikacin, cephalosporins, fluoroquinolones and β-lactam/β-lactamase inhibitor combinations generally decreased over time. Further monitoring of the susceptibility to ertapenem and other antibiotics through SMART is warranted.

In vitro activity of ertapenem versus ceftriaxone against Neisseria gonorrhoeae isolates with highly diverse ceftriaxone MIC values and effects of ceftriaxone resistance determinants: ertapenem for treatment of gonorrhea?

Clinical resistance to the currently recommended extended-spectrum cephalosporins (ESCs), the last remaining treatment options for gonorrhea, is being reported. Gonorrhea may become untreatable, and new treatment options are crucial. We investigated the in vitro activity of ertapenem, relative to ceftriaxone, against N. gonorrhoeae isolates and the effects of ESC resistance determinants on ertapenem. MICs were determined using agar dilution technique or Etest for international reference strains (n = 17) and clinical N. gonorrhoeae isolates (n = 257), which included the two extensively drug-resistant (XDR) strains H041 and F89 and additional isolates with high ESC MICs, clinical ESC resistance, and other types of clinical high-level and multidrug resistance (MDR). Genetic resistance determinants for ESCs (penA, mtrR, and penB) were sequenced. In general, the MICs of ertapenem (MIC(50) = 0.032 μg/ml; MIC(90) = 0.064 μg/ml) paralleled those of ceftriaxone (MIC(50) = 0.032 μg/ml; MIC(90) = 0.125 μg/ml). The ESC resistance determinants mainly increased the ertapenem MIC and ceftriaxone MIC at similar levels. However, the MIC ranges for ertapenem (0.002 to 0.125 μg/ml) and ceftriaxone (<0.002 to 4 μg/ml) differed, and the four (1.5%) ceftriaxone-resistant isolates (MIC = 0.5 to 4 μg/ml) had ertapenem MICs of 0.016 to 0.064 μg/ml. Accordingly, ertapenem had in vitro advantages over ceftriaxone for isolates with ceftriaxone resistance. These in vitro results suggest that ertapenem might be an effective treatment option for gonorrhea, particularly for the currently identified ESC-resistant cases and possibly in a dual antimicrobial therapy regimen. However, further knowledge regarding the genetic determinants (and their evolution) conferring resistance to both antimicrobials, and clear correlates between genetic and phenotypic laboratory parameters and clinical treatment outcomes, is essential.

In Vitro Activities of Ertapenem and Imipenem against Clinical Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae Collected in Military Teaching Hospital Mohammed V of Rabat

Objective. To study the sensitivity level of extended spectrum beta-lactamase-producing Enterobacteriaceae to Carbapenems (Imipenem, Ertapenem) marketed in Morocco and discusses the place of Ertapenem in the treatment of extended spectrum-beta-lactamase-producing. Materials and Methods. A retrospective study of 110 extended spectrum beta-lactamase-producing Enterobacteriaceae. Isolates obtained from blood cultures, superficial and deep pus, and catheters were conducted. The minimum inhibitory concentrations of Imipenem and Ertapenem were done by the E-test. The modified Hodge test was conducted for resistant or intermediate strains. Results. 99.1% of isolates were susceptible to Imipenem. For Ertapenem, 4 were resistant and 4 intermediate. The modified Hodge test was positive for all 08 isolates. A minimum inhibitory concentration comparison of K. pneumoniae, E. cloacae, and E. coli for Imipenem has noted a significant difference between E. cloacae on one hand and E. coli, K. pneumoniae on the other hand (P < 0.01). No significant difference was noted for minimum inhibitory concentration of Ertapenem. Conclusion. Our results confirm in vitro effectiveness of Ertapenem against extended spectrum beta-lactamase-producing Enterobacteriaceae as reported elsewhere. However, the emergence of resistance to Carbapenems revealed by production of carbapenemases in this study confirmed a necessary bacteriological documented infection before using Ertapenem.

Trending Eight Years of In Vitro Activity of Ertapenem and Comparators Against Escherichia Coli from Intra-abdominal Infections in North America—SMART 2002-2009

During 2002 – 2009, 2,885 Escherichia Coli intra-abdominal isolates were collected from North America in the Study for Monitoring Antimicrobial Resistance Trends(SMART) surveillance program. The incidence of extended-spectrum beta-lactamase producing isolates ranged from 1.7% in 2005 to 7.2% in 2004 and 2006, and was 6.8% in 2009. Susceptibility trends showed that there were only minor fluctuations in susceptibility to ertapenem and imipenem with no significant decrease over time. By contrast, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftri-axone, ciprofloxacin, and levofloxacin exhibited significantly higher minimum inhibitory concentrations against E. coli overall (p>0.05) and (except for cefoxitin) against extended-spectrum beta-lactamase producing isolates. Piperacillin-tazobactam also had significantly diminished activity against E. coli overall, but paradoxically showed significantly increased activity against extended-spectrum beta-lactamase producing isolates. Ertapenemand imipenem susceptibility of E. coli in North America remained consistently high during the period 2002 through 2009, and continuing updates from SMART will be helpful in detecting any changes that occur in the future.

Comparison of in vitro activity of ertapenem with other carbapenems against extended-spectrum beta-lactamase-producing Escherichia coli and Kleibsella species isolated in a tertiary children's hospital

Objective: The purpose of this study was to evaluate the susceptibility of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae clinical isolates to ertapenem in a tertiary pediatric care center in Turkey.Design/methods: All isolates of ESBL-producing Enterobacteriaceae were collected from clinical specimens from children, and susceptibility tests were done using the Vitek 2 compact system.Results: Ninety-nine per cent of the ESBL-producing Escherichia coli isolates were found to be susceptible to ertapenem, 99.5% to imipenem and 100% to meropenem. In the Klebsiella species, 91.5% of the isolates were susceptible to ertapenem, 99.3% to imipenem and 100% to meropenem.Conclusion: The results of our data, including isolates from children, showed that ertapenem had high in vitro activity against the majority of the ESBL-producing E. coli and Klebsiella species, as reported in previously published studies. However, additional clinical studies are required to assess the clinical activity of ertapenem and the clinical importance of the resistant isolates.

Actividad comparativa del ertapenem frente a Klebsiella pneumoniae productor de betalactamasas de espectro extendido o betalactamasas de AmpC plasmídicas: efecto inóculo y papel de la pérdida de porinas

The effect of porin loss and inoculum size on the comparative activity of ertapenem against either extended-spectrum beta lactamase-producing (ESBL) or plasmid-mediated AmpC beta lactamase-producing (pACBL) Klebsiella pneumoniae strains was evaluated. Microdilution using 2 different bacterial inocula. Imipenem, amikacin, ertapenem, and cefepime were the most active agents under standard conditions. Ertapenem was more highly affected by porin loss than imipenem. Ertapenem showed high activity against K. pneumoniae strains expressing ESBL, pACBL or both. Strains deficient in porins showed decreased susceptibility to beta lactams. The inoculum effect had a greater impact on imipenem than on ertapenem.

Infection after Elective Colorectal Surgery: Bacteriological Analysis of Failures in a Randomized Trial of Cefotetan vs. Ertapenem Prophylaxis

A randomized study comparing single-dose cefotetan and ertapenem prophylaxis for elective colorectal surgery in 1,002 patients found ertapenem to be significantly more effective (p < 0.001). Failures of prophylaxis were thought to involve organisms resistant to both antimicrobial agents, isolated most often from deep or superficial incision sites. Further testing and analysis of the microbial data was performed. Susceptibility results were correlated with the clinical outcomes reported previously. Of the 216 aerobes tested, 62.6% were resistant to cefotetan and 44% to ertapenem. Enterococci and methicillin-resistant Staphylococcus epidermidis were the aerobes recovered most frequently, and Bacteroides thetaiotaomicron, Clostridium innocuum, and Eubacterium lentum were the most frequent anaerobes. Enterococcus faecalis usually was associated in mixed culture with Bacteroides fragilis group species. Approximately one-half of the 158 anaerobes (50.7%), including all the species above, were resistant to cefotetan; most of these (61.4%) came from superficial incision sites. Only one anaerobe (Desulfovibrio fairfieldensis), found in a superficial incisional infection, was resistant to ertapenem, and no ertapenem-resistant enteric bacteria were recovered. In vitro resistance was associated with therapeutic failure. The in vitro activity of ertapenem was superior to that of cefotetan against all anaerobic and many aerobic bacteria isolated from postoperative cultures of patients who failed prophylaxis with these agents. Our findings help to elucidate the results of the clinical trial.