Minimum Inhibitory Concentration Distributions Research Articles

Increasing Incidence of High-Level Tetracycline-Resistant Neisseria gonorrhoeae due to Clonal Spread and Foreign Import.

PurposeThe detection of high-level tetracycline-resistant strains of Neisseria gonorrhoeae (TRNG) can make important epidemiological contributions that are relevant to controlling infections from this pathogen. In this study, we aimed to determine the incidence of TRNG isolates over time and also to investigate the characteristics and genetic epidemiology of these TRNG isolates in Korea.Materials and MethodsThe antimicrobial susceptibilities of 601 isolates of N. gonorrhoeae from 2004 to 2011 were tested by standard Clinical and Laboratory Standards Institute methods. To determine the molecular epidemiological relatedness, N. gonorrhoeae multi-antigen sequence typing was performed.ResultsThe incidence of TRNG increased from 2% in 2004 to 21% in 2011. The minimum inhibitory concentration distributions of ceftriaxone and susceptibility of ciprofloxacin in TRNG were different from non-TRNG and varied according to the year of isolation. Most of the TRNG isolates collected from 2004 to 2007 exhibited genetic relatedness, with sequence type (ST) 1798 being the most common. From 2008 to 2011, the STs of the isolates became more variable and introduction of genetically unrelated TRNG were noted.ConclusionThe increased incidence of TRNG strains until 2007 appears to be due, at least in part, to clonal spread. However, we propose that the emergence of various STs since 2008 could be associated with foreign import.

Rifaximin combined with polymyxins: A potential regimen for selective decontamination of multidrug-resistant bacteria in the digestive tract?

Selective decontamination of the digestive tract (SDD) using combinations of oral non-absorbable antibiotics has been proposed as a means of preventing multidrug-resistant (MDR) infections. The minimum inhibitory concentrations (MICs) of rifaximin (RIFAX) were determined against 262 Gram-negative and Gram-positive bacterial isolates by broth microtitre assay. Rifampicin (RIF) was used as a comparator in the analysis. Synergistic interactions between RIFAX and polymyxin B (PMB) were assessed by using the chequerboard method and calculating the fractional inhibitory concentration index (FICI). The antimicrobial activities of both RIFAX and RIF were similar with little variation in the overall MIC distributions for Gram-negative non-fermenters and Gram-positive bacteria. However, against Enterobacteriaceae higher MICs (>16mg/L) were observed for RIFAX than for RIF (50% vs 27%). Amongst the 262 isolates tested, 100 could be considered resistant to RIFAX. Overall, the combination of RIFAX and PMB was more active against all of the isolates tested compared with either drug alone, with reductions of 2-11 doubling dilutions in individual MICs. Potent synergy was observed with the RIFAX+PMB combination using FICI criteria (FICI range 0.02-0.5). The data presented here suggest that combination therapy may be significantly more effective against isolates with RIFAX and/or PMB resistance and could be considered as part of a SDD regimen aimed at reducing enteric carriage of MDR pathogens in colonised and infected patients.

Defining the frontiers between antifungal resistance, tolerance and the concept of persistence.

A restricted number of antifungal agents are available for the therapy of fungal diseases. With the introduction of epidemiological cut-off values for each agent in important fungal pathogens based on the distribution of minimal inhibitory concentration (MIC), the distinction between wild type and drug-resistant populations has been facilitated. Antifungal resistance has been described for all currently available antifungal agents in several pathogens and most of the associated resistance mechanisms have been deciphered at the molecular level. Clinical breakpoints for some agents have been proposed and can have predictive value for the success or failure of therapy. Tolerance to antifungals has been a much more ignored area. By definition, tolerance operates at antifungal concentrations above individual intrinsic inhibitory values. Important is that tolerance to antifungal agents favours the emergence of persister cells, which are able to survive antifungal therapy and can cause relapses. Here we will review the current knowledge on antifungal tolerance, its potential mechanisms and also evaluate the role of antifungal tolerance in the efficacy of drug treatments.

The impact of revised CLSI cefazolin breakpoints on the clinical outcomes of Escherichia coli bacteremia.

The susceptibility breakpoints of cephalosporins for Enterobacteriaceae were revised by the Clinical and Laboratory Standards Institute (CLSI) in 2010 and 2011. The clinical outcome and susceptibility data were analyzed to evaluate the impact of revised CLSI cefazolin breakpoints on the treatment of Escherichia coli bacteremia. Forty-three bacteremic Escherichia coli isolates from Taichung Veterans General Hospital, Taichung, Taiwan, during the period from January 2013 to December 2013, were selected to analyze the minimum inhibitory concentration (MIC) distributions of cefazolin and the correlated clinical responses to cefazolin therapy. The modal cefazolin MIC among the 43 isolates was 1μg/mL and accounted for 18 (42%) isolates. The cumulative percentage for MICs ≤ 2μg/mL was 79%. The conventional dosing regimens achieved clinical cure in 33 (97%) of 34 patients with bacteremia due to E. coli with a cefazolin MIC ≤ 2μg/mL, in all of the six patients with a cefazolin MIC of 4μg/mL, and all of the three patients with a cefazolin MIC of 8μg/mL. The microbiological data support the revised CLSI breakpoints of cefazolin. The conventional cefazolin dosing regimens can still achieve satisfactory clinical cure rates for bacteremia of E. coli with a cefazolin MIC ≤ 2μg/mL in patients without severe septic shock. Before the approval of the efficacy of cefazolin for the treatment of E. coli isolates with a cefazolin MIC of 4μg/mL, it is prudent to use cefazolin only when a high drug level can be achieved in the infection site, such as the urinary tract.

The association of molecular typing, vancomycin MIC, and clinical outcome for patients with methicillin-resistant Staphylococcus aureus infections.

There are reports of an increase in vancomycin minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA) over time, a phenomenon referred to as "MIC creep", but some studies have conflicting results. The aim of this study is to evaluate the association of molecular typing, vancomycin MIC, and clinical outcome for patients with MRSA infections. Thirty-two MRSA isolates from Taichung Veterans General Hospital (TCVGH), Taichung, Taiwan during the period of 2003 to 2008 were analyzed for the association of sequence typing, vancomycin MIC, and the correlated clinical outcome for patients with MRSA infections. The vancomycin MICs of 28 additional isolates from 2014 were used for the detection of MIC creep. Among the genotypes of 32 isolates, there were 17 (53.1%) isolates with ST239-SCCmecIII, seven (21.9%) isolates with ST5-SCCmecII, six (18.8%) isolates with ST59-SCCmecIV, and two (6.2%) isolates with ST59-SCCmecVT. Two isolates had an MIC of 2μg/mL and were identified as ST239-SCCmecIII. No statistically significant change in the distribution of MICs of all isolates was observed between 2003 and 2014 (p=0.263). There was no significant difference in the mortality rates between two groups of patients with vancomycin MICs <2μg/mL and ≥ 2μg/mL (p =>0.99). There was no vancomycin MIC creep in the period from 2003 to 2014 in this study. Appropriate prognostic models for assessment of the association among sequence types, vancomycin MICs, and clinical outcome warrant further investigation.

Prediction of Pharmacokinetics and Pharmacodynamics of Doripenem in Pediatric Patients

The aim of this paper was to predict the pharmacokinetics of doripenem in pediatrics from adult pharmacokinetic data and to investigate dosing regimens in pediatrics using Monte-Carlo pharmacokinetics/pharmacodynamics (PK/PD) simulations prior to the initiation of pediatric clinical trials. The pharmacokinetics in pediatrics was predicted by using a previously reported approach for β-lactam antibiotics. Monte-Carlo simulation was employed to assess dosing regimens in pediatrics based on the predicted pharmacokinetic profiles and the minimum inhibitory concentration (MIC) distributions of Haemophilus influenzae and Streptococcus pneumoniae, which frequently cause infectious pediatric diseases. The probabilities of attaining target time above MIC (40%T>MIC) were calculated for dosing regimens of 1-30 mg/kg with two or three times daily dosing (TID) based on simulations of 5000 pediatric patients and MICs. The results suggested 15 and 5 mg/kg TID would give approximately 90% or more probability of target attainment against Haemophilus influenzae and Streptococcus pneumoniae, respectively. The pediatric phase 3 study confirmed that pharmacokinetics in pediatrics could be well predicted by this method, indicating that the dosing regimen had been appropriately selected. The framework of dose selection for pediatric clinical trials based on predictions of pharmacokinetic profiles and PK/PD indices should be applicable to the development of other β-lactam antibiotics for pediatric use.

Epidemiology of Staphylococcus aureus in Italy: First nationwide survey, 2012.

A 3-month epidemiological study to determine the prevalence and antibiotic resistance of Staphylococcus aureus nosocomial infections was performed in 52 centres throughout Italy in 2012. A total of 21,873 pathogens were analysed. The prevalence of S. aureus among all nosocomial pathogens isolated in that period was 11.6% (n=2541), whilst the prevalence of methicillin-resistant S. aureus (MRSA) among the S. aureus was 35.8% (n=910). All tested antimicrobials demonstrated ≥92.2% susceptibility against methicillin-susceptible S. aureus, with the exception of clindamycin (89.7%) and erythromycin (84.2%). Among MRSA, percentages of resistance ranged from 12.6% to >39% for tetracycline, rifampicin, clindamycin and gentamicin; higher percentages were found for erythromycin (65.4%) and fluoroquinolones (72.3-85.8%). Overall, the glycopeptide minimum inhibitory concentration (MIC) distribution showed that 58.3% of strains possessed MICs of 1-2mg/L and few strains were linezolid- or daptomycin-resistant. Molecular characterisation was performed on 102 MRSA selected from Northern, Central and Southern regions. Five major clones were found: Italian/ST228-I (t001-t023-t041-t1686-t3217), 33.3%; USA500/ST8-IV (t008), 17.6%; E-MRSA15/ST22-IVh (t020-t025-t032-t223), 16.7%; USA100/ST5-II (t002-t653-t1349-t2164-t3217-t388), 14.7%; and Brazilian/ST239/241-III (t030-t037), 3.9%. Five PVL-positive CA-MRSA isolates, belonging to USA300 and minor clones, were also identified. In conclusion, this first nationwide surveillance study showed that in Italy, S. aureus infections accounted for 11.6% of all nosocomial infections; MRSA accounted for approximately one-third of the S. aureus isolates and these were multidrug-resistant organisms. Five major MRSA epidemic clones were observed and were inter-regionally distributed, with ST228-SCCmecI becoming predominant.

Characterization of Escherichia coli Isolates from an Urban Lake Receiving Water from a Wastewater Treatment Plant in Mexico City: Fecal Pollution and Antibiotic Resistance.

The presence of enteric bacteria in water bodies is a cause of public health concerns, either by directly causing water- and food-borne diseases, or acting as reservoirs for antibiotic resistance determinants. Water is used for crop irrigation; and sediments and aquatic plants are used as fertilizing supplements and soil conditioners. In this work, the bacterial load of several micro-environments of the urban lake of Xochimilco, in Mexico City, was characterized. We found a differential distribution of enteric bacteria between the water column, sediment, and the rhizoplane of aquatic plants, with human fecal bacteria concentrating in the sediment, pointing to the need to assess such bacterial load for each micro-environment, for regulatory agricultural purposes, instead of only the one of the water, as is currently done. Resistance to tetracycline, ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole was common among Escherichia coli isolates, but was also differentially distributed, being again higher in sediment isolates. A distinct distribution of chloramphenicol minimum inhibitory concentrations (MIC) among these isolates suggests the presence of a local selective pressure favoring lower MICs than those of isolates from treated water. Fecal bacteria of human origin, living in water bodies along with their antibiotic resistance genes, could be much more common than typically considered, and pose a higher health risk, if assessments are only made on the water column of such bodies.

Azole susceptibility of Malassezia pachydermatis and Malassezia furfur and tentative epidemiological cut-off values.

This study aims to determine the minimal inhibitory concentration (MIC) distribution and the epidemiological cut-off values (ECVs) of Malassezia pachydermatis and Malassezia furfur isolates for fluconazole (FLZ), itraconazole (ITZ), posaconazole (POS), and voriconazole (VOR). A total of 62 M. pachydermatis strains from dogs with dermatitis and 78 M. furfur strains from humans with bloodstream infections (BSI) were tested by a modified broth microdilution Clinical and Laboratory Standards Institute (CLSI) method. ITZ and POS displayed lower MICs than VOR and FLZ, regardless of the Malassezia species. The MIC data for azoles of M. pachydermatis were four two-fold dilutions lower than those of M. furfur. Based on the ECVs, about 94% of Malassezia strains might be categorized within susceptible population for all azoles, except for FLZ, and azole cross-resistance was detected in association with FLZ in M. pachydermatis but not in M. furfur.The study proposes, for the first time, tentative azole ECVs for M. pachydermatis and M. furfur for monitoring the emergence of isolates with decreased susceptibilities and shows that the azole MIC distribution varied according to the Malassezia species tested, thus suggesting the usefulness of determining the susceptibility profile for effective treatment of each species.

Antimicrobial susceptibility patterns of clinical Escherichia coli isolates from dogs and cats in the United States: January 2008 through January 2013

Escherichia coli is among the most common bacterial pathogens in dogs and cats. The lack of a national monitoring program limits evidence-based empirical antimicrobial choices in the United States. This study describes antimicrobial susceptibility patterns for presumed clinical E. coli isolates from dogs (n=2392) or cats (n=780) collected from six geographic regions in the United States between May 2008 and January 2013. Minimum inhibitory concentrations (MIC) were determined for 17 drugs representing 6 drug classes. Urinary tract isolates were most common (71%). Population MIC distributions were generally bimodal with the second mode above the resistant breakpoint for all drugs except gentamicin, amikacin, and meropenem. The MIC90 exceeded the susceptible breakpoint for ampicillin, amoxicillin–clavulanic acid, cephalothin (surrogate drug for cephalexin), and doxycycline but was below the susceptible breakpoint for all others. None of isolates was susceptible or resistant to all drug tested; 46% were resistant to 1 or 2 antimicrobial categories, and 52% to more than three categories. The resistance percentages were as follows: doxycycline (100%), cephalothin (98%)>ampicillin (48%)>amoxicillin–clavulanic acid (40%)>ticarcillin–clavulanic acid (18%)>cefpodoxime (13%), cefotaxime (12%), cefoxitin (11%), cefazolin (11%), enrofloxacin (10%), chloramphenicol (9.6%)>ciprofloxacin (9.2%), ceftazidime (8.7%), trimethoprim–sulfamethoxazole (7.9%), gentamicin (7.9%)>meropenem (1.5%), amikacin (0.7%) (P<0.05). Resistance to ampicillin and amoxicillin–clavulanic acid was greatest in the South-Central region (P<0.05). E. coli resistance may preclude empirical treatment with doxycycline, cephalexin, ampicillin, or amoxicillin–clavulanic acid. Based on susceptibility patterns, trimethoprim–sulfonamides may be the preferred empirical oral treatment.

The Prevalence of Vancomycin-Intermediate Staphylococcus aureus and Heterogeneous VISA Among Methicillin-Resistant Strains Isolated from Pediatric Population in a Turkish University Hospital.

There are limited data regarding the prevalence of vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) among pediatric population. Our objective was to determine the distribution of vancomycin and daptomycin minimum inhibitory concentrations (MICs) and explore the phenomenon of vancomycin MIC creep and the VISA/hVISA prevalence among the methicillin-resistant Staphylococcus aureus (MRSA) strains belonging to pediatric population by population analysis profile-area under the curve (PAP-AUC) and Etest macromethod. Vancomycin and daptomycin susceptibilities of 94 pediatric isolates of MRSA were tested by broth microdilution (BMD) and Etest methods. To determine the prevalence of VISA/hVISA, Etest macromethod and PAP-AUC was performed on all isolates. All isolates were susceptible to vancomycin and daptomycin by both BMD and Etest methods. Twenty-eight (29.8%) isolates had vancomycin MICs of 2 μg/ml by BMD. No increase in vancomycin MICs was observed over time. There were no VISA among 94 MRSA tested but 20 (21.3%) hVISA isolates were identified by PAP-AUC. Results of Etest macromethod were compared to PAP-AUC. Etest macromethod was 60.0% sensitive and 90.5% specific. The hVISA isolates represented 53.6% of isolates with vancomycin MICs of 2 μg/ml. Also, 75% of hVISA isolates had vancomycin MICs of 2 μg/ml. To our knowledge, this is the first study investigating the prevalence of VISA/hVISA among MRSA isolated from pediatric patients by PAP-AUC method. Based on our findings, MRSA isolates, which have vancomycin MIC of 2 μg/ml can be investigated for the presence of hVISA. In this study, daptomycin showed potent activity against all isolates and may represent a therapeutic option for MRSA infections.

In vitro activity of two amphotericin B formulations against Malassezia furfur strains recovered from patients with bloodstream infections.

Although guidelines for the treatment of Malassezia furfur fungemia are not yet defined, clinical data suggest that amphotericin B (AmB) is effective for treating systemic infections. In the absence of clinical breakpoints for Malassezia yeasts, epidemiological cut-off values (ECVs) are useful to discriminate between isolates with and without drug resistance. This study aimed to compare the distribution of minimal inhibitory concentration (MIC) and the ECVs for AmB of both deoxycholate (d-AmB) and liposomal (l-AmB) formulations of M. furfur isolates. The 84 M. furfur strains analyzed, which included 56 from blood, sterile sites and catheters, and 28 from skin, were isolated from patients with bloodstream infections. MICs were determined by the modified broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI). The l-AmB MIC and the ECVs were two-fold lower than those of d-AmB and a lower l-AmB mean MIC value was found for blood isolates than from skin. The ECVs for l-AmB and d-AmB were 8 mg/l and 32 mg/l, respectively. Three strains (3.6%) showed l-AmB MIC higher than ECV (MIC>8 mg/l) of which two were isolated from the catheter tip of patients treated with micafugin, l-Amb and fluconazole, and one from skin. The results showed that the l-AmB might be employed for assessing the in vitro antifungal susceptibility of M. furfur by a modified CLSI protocol and that ECVs might be useful for detecting the emergence of resistance.

Rates of susceptibility of carbapenems, ceftobiprole, and colistin against clinically important bacteria collected from intensive care units in 2007: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).

Data on susceptibility to ceftobiprole and colistin, and the complete evolutionary trends of minimum inhibitory concentrations (MICs) of important carbapenem agents among important pathogens collected in intensive care units (ICUs) in Taiwan are lacking. We surveyed the MIC distribution patterns of ceftobiprole and colistin and susceptibility profiles of some important pathogens collected from patients hospitalized in intensive care units (ICUs) of major teaching hospitals throughout Taiwan in 2007. We also investigated the rates of nonsusceptibility to powerful carbapenems (imipenem, meropenem) among four important species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis) collected during the same period. MIC breakpoints recommended by the Clinical and Laboratory Standards Institute in 2014 were applied. Colistin showed excellent invitro activity (susceptibility rate, 96%) against Acinetobacter baumannii isolates but moderate (73-77% susceptibility rate) activity against isolates of Pseudomonas aeruginosa and E. cloacae. The ceftobiprole MIC90 value was 4μg/mL for methicillin-resistant Staphylococcus aureus and 16μg/mL for P. aeruginosa. The phenotype of methicillin resistance did not markedly increase the MIC value of ceftobiprole among S. aureus isolates. Interestingly, the proportion of isolates that displayed nonsusceptibility to imipenem was significantly higher among P. mirabilis isolates than among isolates of the other three Enterobacteriaceae species, regardless of the production of extended-spectrum β-lactamase. Continuous monitoring of susceptibility profiles of ICU pathogens to important antibiotics is warranted to provide appropriate antimicrobial regimens against infections in the ICU.

Determination of the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of selected antimicrobials in bovine and swine Pasteurella multocida, Escherichia coli, and Staphylococcus aureus isolates

We compared the values of the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) values ​​of three antimicrobial agents for 72 bovine isolates ofPasteurella multocida, 80 swine isolates ofP. multocida, 80 bovine isolates ofEscherichia coli, 80 swine isolates ofE. coli, and 80 isolates ofStaphylococcus aureusfrom bovine mastitis. The ratio of MIC90​​/MPC90which limited mutant selection window (MSW) was ≤ 0.12/4 mg/l for enrofloxacin, 0.5/≥ 64 mg/l for florfenicol and 4/≥ 128 mg/l for tulathromycin in bovineP. multocidaisolates, ≤ 0.12/2 mg/l for enrofloxacin, 0.5/≥ 64 mg/l for florfenicol and 4/≥ 128 mg/l for tulathromycin in swineP. multocidaisolates, 1/16 mg/l for enrofloxacin, 8/≥ 64 mg/l for florfenicol and 8/≥ 128 mg/l for tulathromycin in bovineE. coliisolates, 0.5/16 mg/l for enrofloxacin, ≥ 64/≥ 64 mg/l for florfenicol and 8/≥ 128 mg/l for tulathromycin in swineE. coliisolates, and 0.25/16 mg/l for enrofloxacin, 4/≥ 64 mg/l for florfenicol and 4/≥ 128 mg/l for tulathromycin inS. aureusisolates. These findings indicate that the dosage of antimicrobial agents to achieve serum concentration equal to or higher than MPC could reduce selection of resistant bacterial subpopulation.

Antibiotic susceptibility of Clostridium difficile is similar worldwide over two decades despite widespread use of broad-spectrum antibiotics: an analysis done at the University Hospital of Zurich.

BackgroundClostridium difficile infection (CDI) remains a major health problem worldwide. Antibiotic use, in general, and clindamycin and ciprofloxacin, in particular, have been implicated in the pathogenesis of CDI. Here, we hypothesized that antibiotics that are highly active in vitro against C. difficile are less frequently associated with CDI than others. The primary goals of our study were to determine if antibiotic susceptibility and CDI are associated and whether the antimicrobial susceptibility of C. difficile changed over the years.Methods and resultsWe examined a large panel of C. difficile strains collected in 2006-2008 at the University Hospital of Zurich. We found that the antimicrobial susceptibilities to amoxicillin/clavulanate, piperacillin/tazobactam, meropenem, clindamycin, ciprofloxacin, ceftriaxone, metronidazole and vancomycin were similar to those reported in the literature and that they are similar to those reported in other populations over the last two decades. Antibiotic activity did not prevent CDI. For example, thre use of meropenem, which is highly active against all strains tested, was a clear risk factor for CDI. Most of the antibiotics tested also showed a higher minimum inhibitory concentration distribution than that of EUCAST. All strains were susceptible to metronidazole. One strain was resistant to vancomycin.ConclusionsAntibiotic susceptibilities of the collection of C. difficile from the University Hospital of Zurich are similar to those reported by others since the 1980. Patients treated with carbapenems and cephalosporins had the highest risk of developing CDI irrespective of the antimicrobial activity of carbapenems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0607-z) contains supplementary material, which is available to authorized users.

Meropenem-clavulanate has high in vitro activity against multidrug-resistant Mycobacterium tuberculosis

Aims and objectivesWith the relentless increase in multidrug- and extensively-drug resistant tuberculosis (MDR/XDR-TB), new treatment strategies are necessary. Favorable results have been reported by combining a β-lactam antibiotic and a β-lactamase inhibitor. The β-lactamase encoded by the blaC gene of Mycobacterium tuberculosis (MTB) is the major mechanism of resistance to β-lactam antibiotics (e.g., penicillin). Meropenem, a β-lactam antibiotic of the carbapenem group, is a relatively weak substrate for the β-lactamase of MTB. The β-lactamase inhibitor clavulanate irreversibly inactivates the β-lactamase encoded by the blaC gene, thus making the combination of meropenem and clavulanate an interesting treatment alternative for MTB. However, very few isolates of MTB have been tested for this drug combination and few clinical reports exist. Thus, the present study investigates the in vitro activity of meropenem-clavulanate for drug-resistant MTB isolates, including MDR/XDR-TB. MethodsThe minimum inhibitory concentration (MIC) distribution of meropenem-clavulanate was determined using Middlebrook 7H10, including MDR and XDR strains of MTB (n=68). Meropenem was prepared in a stock solution with a final concentration range of 0.002–512mg/L. Clavulanate was added at a fixed concentration of 64mg/L, to avoid a decline of the β-lactamase to insufficient levels during the experiment. All isolates were evaluated after three weeks of growth. The pan-susceptible strain H37Rv was used as a control. ResultsThere was a Gaussian MIC-distribution between 0.125 and 2mg/L of meropenem-clavulanate (expressed as the concentration of meropenem), but four isolates had very high MIC levels (16 and 32mg/L), which is likely to be out of reach in clinical doses (Fig. 1). The susceptibility of the isolates to meropenem-clavulanate was not correlated to the level of resistance to first- or second-line anti-tuberculous drugs. The MIC of the pan-susceptible control strain H37Rv was 1mg/L of meropenem, when combined with clavulanate. ConclusionsThe present study shows that meropenem-clavulanate has low MICs against MTB in vitro, including MDR and XDR-TB isolates. Meropenem has good tissue penetration and low protein-binding, but requires an intravenous access and is relatively expensive. Meropenem-clavulanate may be a treatment option in selected cases of MDR/XDR-TB, although further clinical studies are warranted.

Impact of revised susceptibility breakpoints on bacteremia of Klebsiella pneumoniae: Minimum inhibitory concentration of cefazolin and clinical outcomes.

The Clinical and Laboratory Standards Institute (CLSI) revised the susceptibility breakpoints of cephalosporins for Enterobacteriaceae in 2010 and 2011. However, there is a lack of clinical data about the correlation of minimum inhibitory concentrations (MICs) and clinical outcome. Data for the distribution of MICs and clinical outcomes were analyzed in this study to evaluate the impact of changes in the CLSI breakpoints on the treatment of Klebsiella pneumoniae bacteremia. Ninety-seven bacteremic K. pneumoniae isolates from Taichung Veterans General Hospital, Taichung, Taiwan were collected for study during the period 2009-2011. The cefazolin MIC was determined by the broth microdilution method according to the recommendations of the CLSI. The MIC distribution of cefazolin and the clinical responses to definitive cefazolin treatment were analyzed. The modal cefazolin MIC among the 97 isolates was 1μg/mL and accounted for 73 (75.3%) isolates. There were 18 (18.6%) isolates with a cefazolin MIC of 2μg/mL. The conventional dosage regimens of cefazolin (1g every 6 hours or 8 hours) achieved a clinical cure in 70 (97.2%) of 72 patients in the group with a cefazolin MIC ≤1μg/mL and in 14 (87.5%) of 16 patients in the group with a cefazolin MIC of 2μg/mL. With the conventional dose, the cumulative clinical cure rate for K. pneumoniae bacteremia with cefazolin MIC ≤2μg/mL was 95.5% (84/88 patients). The conventional cefazolin dose still can result in satisfactory clinical cure rates for bacteremic episodes due to K. pneumoniae with cefazolin MIC ≤2μg/mL, the revised susceptible breakpoint of CLSI 2011.

Antibiotic susceptibility and heterogeneity in technological traits of lactobacilli isolated from Algerian goat's milk.

The objective of this study was to identify and study the heterogeneity of technological traits of lactobacilli from goat's milk of Algeria and to evaluate in vitro their safety aspect. Using API50 CHL system and 16S rDNA sequencing, 51% of strains were assigned as Lactobacillus plantarum, 34% as L. pentosus, 7% as L. rhamnosus and 8% as L. fermentum. A large variability was noted for the acidifying capacity in skim milk after 6, 12 and 24h of incubation. All strains expressed aminopeptidase activity against alanine-ρ-NA and leucine-ρ-NA at different levels. All strains were resistant to vancomycin and most of strains showed more susceptibility to β-lactam antibiotic. High susceptibility toward the inhibitors of protein synthesis was also observed. Minimum inhibitory concentrations data obtained revealed that isolates were susceptible to penicillin and chloramphenicol, and resistant to gentamicin and vancomycin. Minimum inhibitory concentrations distribution of other antibiotics showed variability. The analysis of graphical representation of principal component analysis of technological properties of L. plantarum and L. pentosus strains showed diversity among the isolates. Finally, eight L. plantarum (LAM1, LAM3, LAM21, LAM25, LAM35, LF15, LAM34, and LAM35), four L. pentosus (LAM38, LAM39, LF9 and LF16) and two L. rhamnosus (LF3 and LF10) strains, could be good candidates as adjunct culture in dairy product in Algeria.

Use of linezolid susceptibility test results as a surrogate for the susceptibility of Gram-positive pathogens to tedizolid, a novel oxazolidinone.

BackgroundTedizolid is a novel oxazolidinone antibacterial with potent activity against a wide range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Although tedizolid is approved by the US Food and Drug Administration (FDA) for treatment of patients with acute bacterial skin and skin structure infection, commercial susceptibility testing products for tedizolid are not currently available. This study evaluated the usefulness of applying linezolid susceptibility test results as a surrogate for predicting susceptibility to tedizolid in clinically significant Gram-positive pathogens.MethodsGram-positive isolates (N = 10,702) were obtained from annual surveillance programs conducted between 2009 and 2012, from 3 tedizolid clinical trials, and from a preclinical study of the antibacterial activity of tedizolid. Susceptibility testing of linezolid and tedizolid was performed using the reference broth microdilution method in accordance with Clinical and Laboratory Standards Institute methods.ResultsThe minimum inhibitory concentration (MIC) distribution for tedizolid and linezolid against this set of isolates was consistent with that of previous reports. Scatter plot analysis of relevant subsets of organisms was performed and showed high categorical agreement between linezolid and tedizolid MIC results (>99% for staphylococci and streptococci; >98% for enterococci). Very major error rates (ie, tedizolid false-susceptible errors) were very low and within acceptable limits for a surrogate agent: S. aureus and other staphylococcal species, 0%; Enterococcus spp, 0.2%; and Streptococcus spp, 0%.ConclusionsHigh categorical agreement between MIC values for tedizolid and linezolid and low very major error rates were shown for all organism groups tested, supporting the use of linezolid as a reliable surrogate for tedizolid susceptibility testing.

Antibiotic resistance and resistance genes in Escherichia coli from poultry farms, southwest Nigeria.

This study investigated the mechanisms of resistance in 36 E. coli isolated from waste, litter, soil and water samples collected from poultry farms in Southwestern Nigeria. Minimum inhibitory concentration (MIC) distributions of the isolates were determined using the methods of the Clinical and Laboratory Standard Institute and resistance genes detected by PCR. A total of 30 isolates (94%) showed resistance to more than one antimicrobial. Percentage resistance was: tetracycline 81%, sulphamethoxazole 67%, streptomycin 56%, trimethoprim 47 %, ciprofloxacin 42%, ampicillin 36%, spectinomycin 28%, nalidixic acid 25%, chloramphenicol 22%, neomycin 14%, gentamicin 8%, amoxicillin-clavulanate, ceftiofur, cefotaxime, colistin, florfenicol and apramycin 0%. Resistance genes found among the isolates include bla-TEM (85%), sul2 (67%), sul3 (17%), aadA (65%), strA (70%), strB (61%), catA1 (25%), cmlA1 (13%), tetA (21%) and tetB (17%). Class 1 and 2 integrons were found in five (14%) and six (17%) isolates, respectively, while one isolate was positive for both classes of integrons. Seven out of eight isolates with resistance to ciprofloxacin and MIC ≤ 32 mg/L to nalidixic acid contained qnrS genes. Our findings provided additional evidence that the poultry production environment in Nigeria represents an important reservoir of antibiotic resistance genes such as qnrS that may spread from livestock production farms to human populations via manure and water.