Modal Minimum Inhibitory Concentration Research Articles

Mutations in genes lpxL1, bamA, and pmrB impair the susceptibility of cystic fibrosis strains of Pseudomonas aeruginosa to murepavadin.

Murepavadin is a peptidomimetic exhibiting specific inhibitory activity against Pseudomonas species. In the present study, its in vitro activity was assessed on 230 cystic fibrosis (CF) strains of Pseudomonas aeruginosa isolated from 12 French hospitals, in comparison with 12 other antipseudomonal antibiotics. Although murepavadin is still in preclinical stage of development, 9.1% (n = 21) of strains had a minimum inhibitory concentration (MIC) >4 mg/L, a level at least 128-fold higher than the modal MIC value of the whole collection (≤0.06 mg/L). Whole-genome sequencing of these 21 strains along with more susceptible isogenic counterparts coexisting in the same patients revealed diverse mutations in genes involved in the synthesis (lpxL1 and lpxL2) or transport of lipopolysaccharides (bamA, lptD, and msbA), or encoding histidine kinases of two-component systems (pmrB and cbrA). Allelic replacement experiments with wild-type reference strain PAO1 confirmed that alteration of genes lpxL1, bamA, and/or pmrB can decrease the murepavadin susceptibility from 8- to 32-fold. Furthermore, we found that specific amino acid substitutions in histidine kinase PmrB (G188D, Q105P, and D45E) reduce the susceptibility of P. aeruginosa to murepavadin, colistin, and tobramycin, three antibiotics used or intended to be used (murepavadin) in aerosols to treat colonized CF patients. Whether colistin or tobramycin may select mutants resistant to murepavadin or the opposite needs to be addressed by clinical studies.

Etiological Surveillance of Male Urethritis Syndrome in South Africa: 2019 to 2020.

In South Africa, male urethritis syndrome (MUS) is the most common sexually transmitted infection (STI) syndrome in men. We determined the distribution of STI etiologies and the susceptibility profiles of Neisseria gonorrhoeae isolates from men presenting with MUS to 3 sentinel surveillance health care facilities. Secondary objectives were to determine the seroprevalence of coinfections (HIV, syphilis, herpes simplex virus 2). Consecutive, consenting men with symptomatic urethral discharge were enrolled between January 1, 2019, and December 31, 2020. Genital discharge swab and blood specimens were collected and transported to a central STI reference laboratory in Johannesburg, South Africa. Among 769 men enrolled, N. gonorrhoeae was the commonest cause of MUS (674 [87.8%]; 95% confidence interval [CI], 85.2%-89.9%), followed by Chlamydia trachomatis (161 [21.0%]; 95% CI, 18.2%-24.0%). Of 542 cultivable N. gonorrhoeae isolates, all were susceptible to ceftriaxone (modal minimum inhibitory concentration, 0.004 mg/L) and azithromycin (modal minimum inhibitory concentration, 0.128 mg/L). Seroprevalence rates of HIV, syphilis, and HSV-2 were 21.4% (95% CI, 18.5%-24.5%), 2.3%, and 50.1%, respectively. Condom use at last sexual encounter was reported by only 7%, less than 50% had been medically circumcised, and only 66.7% (58 of 87) who self-reported an HIV-positive status were adherent on antiretroviral drugs. Neisseria gonorrhoeae and C. trachomatis were the predominant causes of MUS. Currently recommended dual ceftriaxone and azithromycin therapy are appropriate for MUS syndromic management; however, surveillance must be maintained to timeously detect emerging and increasing gonococcal resistance. Clinic-based interventions must be intensified in men seeing sexual health care to reduce the community transmission and burden of STI and HIV.

Minimum inhibitory concentration of cycloserine against Mycobacterium tuberculosis using the MGIT 960 system and a proposed critical concentration

We aimed to determine the breakpoint of cycloserine (CS) susceptibility in MGIT and to describe the molecular characteristics of CS-resistant Mycobacterium tuberculosis (MTB) isolates. A total of 124 MTB isolates were recruited in our analysis. Minimum inhibitory concentration (MIC) was determined using the MGIT system. The mutations of MTB isolates within alr, ddl, ald, and cycA, potentially conferring CS resistance were analyzed by the whole-genome sequencing. In vitro drug susceptibility testing of isolates with doubling concentrations of CS revealed that the modal MIC values was 4 mg/L for MGIT, accounting for 35.5% (44/124) of isolates tested. Seven isolates harbored mutations conferring CS resistance, consisting of five with alr mutations and two with ald mutations. On the basis of the MIC distributions of wild-type and resistotype populations, we proposed a tentative epidemiologic cut-off value of 16 mg/l. The proportion of CS resistance in extensively drug-resistant TB was significantly higher than that of multidrug-resistant TB. In conclusion, we propose critical concentration for MGIT 960 to properly diagnose CS-resistant MTB and demonstrate that mutations in alr and ald genes are the major mechanism conferring CS resistance in clinical isolates.

1281. An Evaluation of Tebipenem In Vitro Activity Against a Panel of Pseudomonas aeruginosa Isolates with Efflux, AmpC, and OprD Mutations

1281. An Evaluation of Tebipenem <i>In Vitro</i> Activity Against a Panel of <i>Pseudomonas aeruginosa</i> Isolates with Efflux, AmpC, and OprD Mutations

Antimicrobial Activity of Some Essential Oils against Methicillin-Susceptible and Methicillin-Resistant Staphylococcus pseudintermedius-Associated Pyoderma in Dogs.

Simple SummaryPyoderma is one of the most common diseases in dogs, and Staphylococcus pseudintermedius, a Gram-positive coagulase-positive bacterium, represents the most common infectious agent causing canine pyoderma. Since multidrug-resistant S. pseudintermedius strains have become a relevant threat in veterinary medicine, this study aimed to test the antimicrobial properties of some essential oils (EOs) against S. pseudintermedius strains isolated from dogs suffering from pyoderma. The obtained findings demonstrated a clear in vitro efficacy of some tested EOs against clinical methicillin-resistant and methicillin-sensible S. pseudintermedius strains. The applicability and efficacy of EOs in cases of canine pyoderma supported by S. pseudintermedius could be beneficial for both dogs and pet owners, who are inevitably exposed to this zoonotic bacterium.This study aimed to test in vitro the antimicrobial activity of 11 essential oils (EOs) against four methicillin-resistant Staphylococcus pseudintermedius (MRSP) and four methicillin-susceptible S. pseudintermedius (MSSP) clinical isolates. The obtained findings demonstrated a clear in vitro efficacy of some tested EOs against both MRSP and MSSP strains. Particularly, modal minimum inhibitory concentration (MIC) values ranging from 1:2048 v/v for Melissa officinalis against an MSSP strain to 1:256 v/v for Cymbopogon citratus against all MRSP strains were observed. The best results, highlighting a modal MIC value of 1:1024 v/v for all tested isolates, was provided by Cinnamomum zeylanicum. Intriguingly, Cinnamomum zeylanicum showed, in many cases, a correspondence between minimum bactericidal concentration (MBC) and MIC values, indicating that the inhibiting dose is also often bactericidal. Moreover, a mild antibacterial and bactericidal activity against both MRSP and MSSP isolates was detected for the other tested EOs. Considering the zoonotic potential of S. pseudintermedius and the increased dissemination of multidrug-resistant strains, the employment of EOs could be useful for the treatment of canine pyoderma. Since antibiotic resistance has become the most urgent issue, from the perspective of the One Health initiative, alternative therapeutic approaches are desirable to limit the use of antibiotics or to improve the efficacy of conventional therapies.

Performance of polymyxin B Etest in a setting of high prevalence of KPC-producing Klebsiella pneumoniae

ObjectivesPolymyxin resistance has been increasing in many regions, and appropriate determination of polymyxin susceptibility is now a major challenge worldwide. Many clinical laboratories rely on gradient diffusion methods to assess polymyxin susceptibility, although broth microdilution (BMD) is the only method currently recommended by the CLSI and EUCAST. The aim of this study was to assess the performance of the polymyxin B (PMB) Etest in a setting with a high prevalence of KPC-producing Klebsiella pneumoniae (KPC-KP). MethodsA commercial Etest susceptibility testing method was evaluated and compared with the reference BMD method, considering isolates with a minimum inhibitory concentration (MIC) ≤2 mg/L for PMB as susceptible to this drug. A total of 310 clinical KPC-KP isolates were evaluated. ResultsSusceptibility was significantly higher by Etest compared with BMD (82.6% vs. 75.8%). The MIC50, MIC90 and modal MICs for PMB were 0.25, 32 and 0.25 mg/L (27.1%) by BMD and 0.5, 16 and 0.5 mg/L (49.7%) by Etest, respectively. Although categorical agreement was 90.0%, there was poor essential agreement (50.6%). A high rate (34.7%) of very major errors (VMEs) and a relatively low rate (2.1%) of major errors were found. ConclusionThe considerable number of resistant isolates in this study allowed an accurate estimation of VME rates and, consequently, a more comprehensive assessment of susceptibility testing for polymyxins. Etest did not meet fully the acceptance criteria for US FDA requirements. These data do not support the use of this commercial method for determining PMB MICs in carbapenem-resistant Enterobacterales populations.

The European gonococcal antimicrobial surveillance programme (Euro-GASP) appropriately reflects the antimicrobial resistance situation for Neisseria gonorrhoeae in the European Union/European Economic Area

BackgroundEuropean Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA).MethodsWe compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance.ResultsThere was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between − 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from − 9.5 to 2.7%) and ciprofloxacin (from − 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate.ConclusionsThe overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea.

Validation of \u03b2-lactam minimum inhibitory concentration predictions for pneumococcal isolates with newly encountered penicillin binding protein (PBP) sequences

BackgroundGenomic sequence-based deduction of antibiotic minimum inhibitory concentration (MIC) has great potential to enhance the speed and sensitivity of antimicrobial susceptibility testing. We previously developed a penicillin-binding protein (PBP) typing system and two methods (Random Forest (RF) and Mode MIC (MM)) that accurately predicted β-lactam MICs for pneumococcal isolates carrying a characterized PBP sequence type (phenotypic β-lactam MICs known for at least one isolate of this PBP type). This study evaluates the prediction performance for previously uncharacterized (new) PBP types and the probability of encountering new PBP types, both of which impact the overall prediction accuracy.ResultsThe MM and RF methods were used to predict MICs of 4309 previously reported pneumococcal isolates in 2 datasets and the results were compared to the known broth microdilution MICs to 6 β-lactams. Based on a method that specifically evaluated predictions for new PBP types, the RF results were more accurate than MM results for new PBP types and showed percent essential agreement (MICs agree within ±1 dilution) >97%, percent category agreement (interpretive results agree) >93%, major discrepancy (sensitive isolate predicted as resistant) rate < 1.2%, and very major discrepancy (resistant isolate predicted as sensitive) rate < 1.4% for all 6 β-lactams. The identification of new PBP types over time was well approximated by a diminishingly increasing curve (Pearson’s r = 0.99) and minimally impacted overall MIC prediction performance.ConclusionsMIC prediction using the RF method could be an accurate alternative of phenotypic susceptibility testing even in the presence of previously uncharacterized PBP types.

Prevalence of macrolide-lincosamide resistance and multidrug resistance phenotypes in streptococcal isolates causing infections in European hospitals: Evaluation of the in vitro activity of oritavancin and comparator agents.

The aim of this study was to evaluate the prevalence of resistance to erythromycin alone (M) and to erythromycin and clindamycin (cMLSB) as well as multidrug resistance (MDR) phenotypes (resistance to at least three classes of drugs) among clinical enterococci from European countries and adjacent geographic regions. The in vitro activity of oritavancin against these isolates was also evaluated. A total of 2569 streptococci collected from 12 European countries as well as Russia, Turkey and Israel were included. A total of 9.8%, 8.1% and 6.4% of β-haemolytic streptococci (BHS) displayed M, cMLSB and MDR phenotypes, respectively. Oritavancin (99.4-100.0% susceptible) demonstrated modal minimum inhibitory concentration (MIC) (0.03mg/L) and MIC50 (0.03mg/L) values that were the same for all BHS or subsets, including MDR. The oritavancin MIC50 value of 0.06mg/L against Streptococcus dysgalactiae was similar to those of daptomycin and penicillin (MIC50≤0.06mg/L for both). Among viridans group streptococci (VGS), 28.3%, 12.7% and 11.6% showed M, cMLSB and MDR phenotypes, respectively. Oritavancin (99.9-100.0% susceptible; MIC50/90, ≤0.008/0.06mg/L) exhibited potent in vitro activity against VGS and resistant subsets, as did vancomycin (MIC50/90, 0.5/0.5-1mg/L), daptomycin (MIC50/90, 0.25-0.5/0.5-1mg/L) and linezolid (MIC50/90, 0.5-1/1mg/L). In conclusion, rates of resistance phenotypes were higher in VGS than BHS. Oritavancin demonstrated in vitro potencies that were similar to or greater than those of comparators against this recent collection of streptococci, including drug-resistant subsets, from European and adjacent countries.

Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales

ObjectivesTreatment of Neisseria gonorrhoeae is threatened by the emergence of antimicrobial resistance. We analysed data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales to identify...

O035 Is cefixime back? Trends in gonococcal resistance to current and previous front line therapies in England and Wales since the 2011 guideline change

Background/introduction Antimicrobial resistance (AMR) in Neisseria gonorrhoeae threatens effective treatment and infection control. Treatment guidelines for gonorrhoea are revised when the prevalence of resistance to first-line therapy exceeds 5%; in the UK this last occurred in 2011, prompting a treatment guideline change from cefixime to dual therapy with ceftriaxone and azithromycin. Aim(s)/objectives Describe emerging trends in gonococcal resistance to current and previous first-line therapies using data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). Methods GRASP collects N. gonorrhoeae isolates from July–September annually from 27 genitourinary medicine clinics in England and Wales. The minimum inhibitory concentration (MIC) of each isolate to seven antimicrobials is determined, then linked to demographic, clinical and behavioural data. Data from 2011–2014 were considered in this analysis. For each antimicrobial, the test for trend in resistance was determined and MIC distributions were compared using the Kolmogorov–Smirnov test. Results In 2014, there was no ceftriaxone resistance (MIC ≥ 0.125 mg/L), but the modal MIC drifted to 0.004 mg/L from 0.002 mg/L in 2011 (p Discussion/conclusion Despite the decline in resistance in cefixime, the drifting MIC distribution suggests isolates are less susceptible than previous years. Ongoing monitoring of AMR with strong compliance with national treatment guidelines is essential to retain gonorrhoea as a treatable infection.

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.

Linezolid Minimum Inhibitory Concentration (MIC) Creep in Methicillin-Resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; (MRSA) Clinical Isolates at a Single Japanese Center

The aim of this study was to evaluate whether linezolid minimum inhibitory concentration (MIC) creep occurred in Staphylococcus aureus clinical isolates, including methicillin-resistant S. aureus (MRSA), over a recent 5-year period at a single Japanese center. A total of 453 MRSA and 195 methicillin-susceptible S. aureus (MSSA) isolates recovered from inpatients from April 1, 2008 to March 31, 2013 were analyzed. The MIC of linezolid was determined by automated Vitek-2 system. The modal MIC, MIC range, MIC50 and MIC90 (MICs required to inhibit the growth of 50% and 90% of organisms, respectively), geometric mean MIC and percentages of susceptible and resistant isolates were evaluated for each fiscal year. None of the S. aureus isolates were resistant to linezolid. Isolates with an MIC of >1 µg/mL were more common in the MSSA samples than in the MRSA samples (91.3% versus 38.2%, p<0.001). The linezolid geometric mean MIC increased by 0.403 µg/mL (from 1.178 in 2008 to 1.582 in 2012) in the MRSA isolates (p=0.006, r(2)=0.945 according to a linear regression analysis) over the 5-year period; however, no increase was observed in the MSSA isolates. The frequency of MRSA isolates with an MIC of 1 µg/mL decreased (from 76.3% in 2008 to 35.4% in 2012) and the isolates with MICs of >1 µg/mL increased over time (from 23.7% in 2008 to 64.6% in 2012). This report demonstrates the occurrence of linezolid MIC creep, as determined using the geometric mean MIC, in MRSA clinical isolates at a single Japanese center.

Management of serious meticillin-resistant Staphylococcus aureus infections: what are the limits?

Severe (life-threatening) meticillin-resistant Staphylococcus aureus (MRSA) infection continues to be treated with vancomycin despite accumulating evidence of poor outcome, increasing resistance and unachievable pharmacokinetic/pharmacodynamic (PK/PD) targets. The minimum inhibitory concentration (MIC) susceptibility breakpoint for vancomycin was recently reduced to 2mg/L. Whilst the great majority of clinical isolates are thus still classified as susceptible, the available clinical evidence argues for a method-dependent breakpoint of 0.5mg/L (broth dilution) or 1.0mg/L (Etest), which would classify many strains as resistant, or at best intermediate. However, automated susceptibility testing systems are not currently capable of performing accurately at this low level, and such low breakpoints are unsatisfactory because the poor reproducibility of tests (plus or minus one doubling dilution) results in a critical non-reproducibility around the modal MIC of 1mg/L described in most published data. Therefore, vancomycin should be used with caution in severe (life-threatening) staphylococcal disease and the MIC should always be reported by method. Daptomycin is generally preferred for bacteraemia/endocarditis and linezolid for pneumonia. Better outcome data for vancomycin, based on achievable PK/PD targets and using robust MIC tests, are urgently required.

In Vitro Antifungal Activity of Isavuconazole against 345 Mucorales Isolates Collected at Study Centers in Eight Countries

Although mucormycoses (formerly zygomycoses) are relatively uncommon, they are associated with high mortality and treatment options are limited. isavuconazole is a novel, water soluble, broad-spectrum azole in clinical development for the treatment of invasive aspergillosis and candidiasis. The objective of this report was to collate data on the In Vitro activity of isavuconazole against a collection of 345 diverse mucorales isolates, collected and tested at eight study centers in europe, mexico and North America. Each study center undertook minimum inhibitory concentration (MIC) susceptibility testing of their isolates, according to EUCAST or CLSI guidelines. Across all study centers, isavuconazole exhibited MIC50 values of 1-4 mg/L and MIC90 values of 4-16 mg/L against the five genera. there were also marked differences in MIC distributions, which could be ascribed to differences in inoculum and/or endpoint. EUCAST guidelines appeared to generate modal MICs 2-fold higher than CLSI. These results confirm that isavuconazole possesses at least partial antifungal activity against mucorales.

Activity of telithromycin against key pathogens associated with community-acquired respiratory tract infections.

To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections. The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin. In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively. High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.

Comparison of serum antibiotic levels in acne patients receiving the standard or a modified release formulation of minocycline hydrochloride

Serum levels of minocycline hydrochloride were determined by bioassay in a total of 223 acne patients (123 male, 100 female) receiving either the recommended dose (100mg/day) or a high dose (200mg/day) of the standard preparation (101 patients) of a modified release formulation (132 patients). Sera were collected within 6 h of the morning dose 7-10 days after the start of treatment. Mean minocycline serum levels were consistently higher in females than in males, irrespective of dose or formulation. The differences only reached statistical significance (P < 0.05, Student's t-test) in the case of the standard preparation at a dose of 50 mg, b.d. Serum levels were increased significantly in both sexes at the higher dosage of each formulation (P < 0.01) but there was no significant difference between formulations at either dosage. Variation in serum concentrations was not accounted for by variation in body mass. Serum levels above the modal minimum inhibitory concentration (MIC) of minocycline for fully sensitive strains of Propionibacterium acnes I (0.125 micrograms/mL) were recorded in all patients. In contrast, serum levels equal to or greater than the modal MIC of minocycline for resistant propionibacteria (2 micrograms/mL) were recorded in only 17.9% of patients on the low dose standard preparation compared with 55.6% on the high dose standard preparation (P < 0.001, chi 2). Even in females on the high-dose modified release formulation, 32.2% had serum levels below the modal MIC of minocycline for resistant strains. We conclude that, in terms of achievable serum levels over a short time period, there is no advantage of the modified release formulation over the standard preparation of minocycline. Whichever formulation is used, dose manipulation may be necessary to achieve maximum therapeutic benefit, especially in those individuals who are colonized by propionibacteria with reduced sensitivity to minocycline.

Major methodology-dependent discordant susceptibility results for Bacteroides fragilis group isolates but not other anaerobes

Two standardized susceptibility test methods, a broth microdilution (BMD) and agar dilution (AD) method were performed on a total of 441 clinical isolates of anaerobes with ceftizoxime, cefotaxime, ceftriaxone, cefoxitin, piperacillin, and metronidazole. Against the 339 strains of the Bacteroides fragilis group BMD minimum inhibitory concentration (MIC) values were lower than those from AD testing for all the β-lactams. Overall for the B. fragilis group and the β-lactams, the mode MIC values were two- to 64-fold lower, and the MIC 50 values two- to eightfold lower. Resistance rates were 11%–28% higher overall with AD results and were higher especially for non -B. fragilis species. For non-Bacteroides anaerobes no major discrepancies were noted for Prevotella species, Peptostreptococcus species, and Viellonella parvula. With Clostridium species and Eubacterium species, some differences were noted with ceftizoxime because of differences in cut-off points. These data illustrate the magnitude of differences in results produced by the two methods using essentially the same test medium for the B. fragilis group. Fortunately, such major discordant results were not widely noted with other groups of anaerobes.

Evaluation of a semiautomated micro-broth dilution system for determing minimum inhibitory concentrations of antimicrobics.

This study investigates the dispensing and inoculating characteristics of the MIC-2000 micro-broth dilution system and compares its ability to determine minimum inhibitory concentrations with that of the reference macro-broth dilution method. Micro-well filling showed a coefficient of variation of 6.8%, and micro-well inoculating showed a coefficient of variation of 6.1%. The reference macro-broth dilution method showed a coefficient of variation of 2.9% for dispensing and a coefficient of variation of 2.9% for inoculating. Ninety-three and eight tenths per cent of macro-broth minimum inhibitory concentrations duplicated the macro-broth modal value, with 100% falling within +/-1 double-dilution step. Eighty-five per cent of micro-broth minimum inhibitory concentrations duplicated the micro-broth modal value, with 99.8% falling within +/-1 double-dilution step. When the micro-broth results were evaluated using the macro-broth modal minimum inhibitory concentration value as a reference point, 55.8% duplicated the macro-broth modal value, with 4.7% falling above it and the remainder being skewed below it, with 6.2% at -2 double-dilution steps. These findings indicate that minimum inhibitory concentrations measured by the MIC-2000 system are somewhat lower than those of the reference macro-broth method. As a result, the micro-broth minimum inhibitory concentrations show a wider dispersion when referenced to the macro-broth modal minimum inhibitory concentration than when referenced to their own modal value.