Intermediate Minimum Inhibitory Concentration Research Articles

Evaluating outcomes associated with revised fluoroquinolone breakpoints for Enterobacterales urinary tract infections: A retrospective cohort study.

In 2019, minimum inhibitory concentration (MIC) breakpoints of ciprofloxacin and levofloxacin for Enterobacterales were lowered. This study sought to determine whether there is a correlation between MIC and outcomes in those receiving fluoroquinolones (FQs) for urinary tract infections (UTIs) caused by Enterobacterales pathogens. This was a retrospective study of adult patients treated with ciprofloxacin or levofloxacin for a UTI caused by an Enterobacterales pathogen. Patients were placed into low MIC (ciprofloxacin: ≤ 0.25mcg/mL; levofloxacin ≤ 0.5mcg/mL), intermediate MIC (ciprofloxacin: 0.5-2 mcg/mL; levofloxacin: 1-4 mcg/mL), or high MIC groups (ciprofloxacin: > 2 mcg/mL; levofloxacin: > 4 mcg/mL). The primary outcome was UTI recurrence, defined as hospital admission, emergency department or clinic visit due to UTI, or antibiotic prescription within 28days of FQ initiation. A total of 1022 patients were included: 887, 75, and 60 with a low, intermediate, and high MIC, respectively. UTI recurrence within 28days occurred most frequently in the high MIC group (20.5% vs. 25.3% vs. 60%; P < 0.01). Risk factors for UTI recurrence identified by multivariable analysis were those with a high MIC (high vs. low MIC: OR 5.20, 95% CI 2.99-9.05, P < 0.01; high vs. intermediate MIC: OR 4.72, 95%CI 2.22-10.03, P < 0.01), a complicated UTI (OR 1.85, 95% CI 1.35-2.54; P < 0.01), a history of recurrent UTIs (OR 1.84, 95% CI 1.29-2.62; P < 0.01), or a respiratory disorder (OR 1.58, 95% CI 1.04-2.42; P = 0.03). This study supports separate, less stringent FQ MIC breakpoint interpretive criteria for UTIs caused by Enterobacterales pathogens.

Comparing the minimum inhibitory and mutant prevention concentrations of selected antibiotics against animal isolates of Pasteurella multocida and Salmonella typhimurium.

Historically, the use of antibiotics was not well regulated in veterinary medicine. The emergence of antibiotic resistance (ABR) in pathogenic bacteria in human and veterinary medicine has driven the need for greater antibiotic stewardship. The preservation of certain antibiotic classes for use exclusively in humans, especially in cases of multidrug resistance, has highlighted the need for veterinarians to reduce its use and redefine dosage regimens of antibiotics to ensure efficacy and guard against the development of ABR pathogens. The minimum inhibitory concentration (MIC), the lowest concentration of an antibiotic drug that will prevent the growth of a bacterium, is recognised as a method to assist in antibiotic dosage determination. Minimum inhibitory concentrations sometimes fail to deal with first-step mutants in bacterial populations; therefore dosing regimens based solely on MIC can lead to the development of ABR. The mutant prevention concentration (MPC) is the minimum inhibitory antibiotic concentration of the most resistant first-step mutant. Mutant prevention concentration determination as a complementary and sometimes preferable alternative to MIC determination for veterinarians when managing bacterial pathogens. The results of this study focused on livestock pathogens and antibiotics used to treat them, which had a MIC value of 0.25 µg/mL for enrofloxacin against all 27 isolates of Salmonella typhimurium. The MPC values were 0.50 µg/mL, with the exception of five isolates that had MPC values of 4.00 µg/mL. The MPC test yielded 65.52% (18 isolates) Salmonella isolates with florfenicol MICs in the sensitive range, while 11 isolates were in the resistant range. Seventeen isolates (58.62%) of Pasteurella multocida had MIC values in the susceptible range and 41.38% (12 isolates) had an intermediate MIC value. Mutant prevention concentration determinations as done in this study is effective for the antibiotic treatment of bacterial infections and minimising the development of resistance. The MPC method can be used to better control to prevent the development of antibiotic drug resistance used in animals.

Antibiotic resistance of Mycoplasma Synoviae strains isolated in China from 2016 to 2019

BackgroundIn the past decade, Mycoplasma synoviae (M. synoviae) infection has become widely prevalent in China, has caused serious economic losses and has become one of the most important diseases in the chicken industry. Medication is a general approach for the control of M. synoviae infection, but antibiotics are sometimes ineffective in clinical practice. To investigate the sensitivity of M. synoviae to antimicrobials commonly used in the treatment of M. synoviae infection, the antibiotic susceptibility of 32 M. synoviae strains isolated from China from 2016 to 2019 were determined using the minimum inhibitory concentration (MIC) method.ResultsAll isolates had low MIC values for the combination of lincomycin and spectinomycin, pleuromutilin, and macrolides. However, the M. synoviae isolates displayed variance in MICs for doxycycline hydrochloride with a range of 0.25 to 8 μg/mL, and oxytetracycline hydrochloride with a range of 0.5 to 8 μg/mL. Three and one M. synoviae isolates showed intermediate MIC values to doxycycline hydrochloride and oxytetracycline hydrochloride, respectively. High MIC values for enrofloxacin were detected in all isolates with MICs ranging from 4 to 32 μg/mL. Furthermore, comparison of the parC QRDR identified a mutation at nucleotide position 254 (C254T) resulting in a Thr 85 Ile amino acid change in all M. synoviae isolates and the reference strain ATCC 25204 being resistant to enrofloxacin. Moreover, mutations at Glu 804 Gly and Thr 686 Ala of gyrA QRDR were identified in all M. synoviae isolates and ATCC 25204. The mutation in the QRDR of the parE gene resulted in amino acid changes at positions 197 (Pro to Ser) in 27/32 M. synoviae isolates.ConclusionThree nonsynonymous mutations in gyrA and parE were first identified to be related to enrofloxacin resistance. Our results showed that M. synoviae resistance to enrofloxacin is widespread.

Dosage Adjustment for Ceftazidime in Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling.

Physiologically based pharmacokinetic (PBPK) modeling has unique advantages in investigating the pharmacokinetics of drugs in special populations. Our aim is to design optimized dosing regimens for ceftazidime in renally-impaired pediatric patients using PBPK modeling. Models for healthy and renally-impaired adults were developed, verified, and adapted for children to predict ceftazidime exposure in pediatric patients with varying degrees of renal impairment, capturing age- and weight-related pharmacokinetic changes. We derived a dosage-adjusted regimen for renally-impaired children based on pharmacokinetic data and evaluated the pharmacodynamics of ceftazidime. The PBPK models adequately predicted ceftazidime exposures in populations after single- and multi-dose administrations, with fold error values within 1.1 between simulated and observed data. In moderate, severe, and end-stage renally-impaired pediatric patients, the areas under the plasma concentration-time curves (AUCs) were 1.87-fold, 3.56-fold, and 6.19-fold higher, respectively, than in healthy children when treated with the same dose of 50mg/kg. Pharmacodynamic verification indicated that the recommended doses of 28, 15, and 8mg/kg administered three times daily (every 8h) to pediatric patients with moderate, severe, and end-stage renal disease, respectively, were sufficient to attain the target of maintaining the free plasma concentration at or above minimum inhibitory concentration (MIC) during 70% of the dosing interval (70% fT>MIC: nearly 100% target attainment for susceptible MIC of 4mg/L and >70% for intermediate MIC of 8mg/L). Our PBPK model can be an effective tool to support dosing recommendations in pediatric patients with different degrees of renal impairment.

Detection of vancomycin susceptibility among methicillin resistant staphylococcus aureus in a tertiary care hospital

Introduction: Staphylococcus aureus infections in current times have become challenging to treat because of advent of Methicillin Resistant Staphylococcus aureus (MRSA) strains which are concurrently resistant to a wide panel of drugs and posing a threat to clinicians and microbiologists globally. The optimal drug for treatment of such MRSA infections is vancomycin but strains with augmented Minimum Inhibitory concentration (MIC) for this drug also have surfaced. Objectives: To know the frequency of MRSA isolates in various clinical samples with their antimicrobial sensitivity patterns and to equate agar dilution and E-test methods for MIC determination of vancomycin to MRSA strains. Materials and Methods: A total of 50 non repeat clinical isolates of staphylococcus aureus isolates were collected from various clinical specimens and were tested for methicillin resistance using the cefoxitin disc diffusion test (30mg). All MRSA isolates were tested for specific MIC by agar dilution and E-test methods. Results: 29 (58%) isolates were resistant to cefoxitin (MRSA). 13.8% isolates had MIC of 4mg/ml for vancomycin (VISA) by both agar dilution and E-test methods. However by agar dilution method 25 (86.2%) isolates exhibited vancomycin MIC of ? 2 mg/ml and by E-test 68.9% of the isolates showed MIC ? 2 mg/ml. Conclusion: Multidrug resistant MRSA strains are on the rise and alternate drug of choice for these infections; vancomycin also is showing increased MIC so prudent use of this drug is advocated. E-test can detect MRSA strains with intermediate MIC values useful for detection of MIC creep so that vancomycin can be used rationally.

Disinfectant and antimicrobial susceptibility studies of the foodborne pathogen Campylobacter jejuni isolated from the litter of broiler chicken houses

Foodborne illness is an ongoing problem worldwide and is caused by bacteria that invade the food chain from the farm, slaughter house, restaurant or grocery, or in the home and can be controlled by strategies using biocides (antiseptics and disinfectants). Susceptibility profiles were determined for 96 Campylobacter jejuni strains obtained in 2011–2012 from broiler chicken house environments to antimicrobials and disinfectants as per the methods of the Clinical and Laboratory Standards Institute and TREK Diagnostics using CAMPY AST Campylobacter plates. Low prevalence of antimicrobial resistance was observed in C. jejuni strains to tetracycline (TET; 21.9%), ciprofloxacin (CIP; 13.5%), and nalidixic acid (NAL; 12.5%). The resistance profiles had a maximum of 3 antimicrobials, CIP-NAL-TET, with TET being the main profile observed. No cross-resistance was observed between antimicrobials and disinfectants. The C. jejuni strains (99%) were resistant to triclosan, 32% were resistant to chlorhexidine, and they all were susceptible to benzalkonium chloride. The strains had low-level minimum inhibitory concentrations (MICs) to the disinfectants P-128, Food Service Sanitizer, F-25 Sanitizer, Final Step 512 Sanitizer, OdoBan, dioctyldimethylammmonium chloride, didecyldimethylammonium chloride (C10AC), benzyldimethyldodecylammonium chloride (C12BAC), and benzyldimethyltetradecylammonium chloride (C14BAC). Intermediate MICs against DC&R, cetylpyridinium bromide hydrate, hexadecylpyridinium chloride, ethylhexadecyldimethylammonium bromide, and hexadecyltrimethylammonium bromide with elevated intermediate MICs against Tek-Trol, benzyldimethylhexadecylammonium chloride, tris(hydroxylmethyl)nitromethane (THN), and formaldehyde. The highest MIC were obtained for povidone-iodine. The components THN and the benzylammonium chlorides C12BAC and C14BAC were responsible for the inhibition by DC&R. The components C10AC and C12BAC may act synergistically causing inhibition of C. jejuni by the disinfectant P-128. The formaldehyde component in DC&R was not effective against C. jejuni compared with the ammonium chloride components. Its use in disinfectants may result in additional unnecessary chemicals in the environment. Didecyldimethylammonium chloride is the most effective ammonium chloride component against C. jejuni.

Antimicrobial Susceptibility and Multilocus Sequence Typing of Listeria monocytogenes Isolated Over 11 Years from Food, Humans, and the Environment in Italy.

Due to the increasing number of studies reporting the detection of antimicrobial-resistant isolates of Listeria monocytogenes, we sought to determine the antimicrobial susceptibility of L. monocytogenes isolates collected in Italy and find potential correlations to their serotypes and multilocus sequence types (MLST). The antimicrobial susceptibility of 317 L. monocytogenes isolates collected from food, humans, and the environment from 1998 to 2009 was assessed by minimum inhibitory concentration (MIC). Serotyping and MLST was also performed on all isolates. Potential correlations among antimicrobial resistance profiles, serotyping, and MLST were statistically evaluated. Twenty-four percent of L. monocytogenes isolates were resistant to oxacillin, 28.7% intermediate to clindamycin, and 24.3% to ciprofloxacin. The majority of isolates with elevated MIC to oxacillin was of environmental origin and belonged to serotype 4b/4e and ST2. Isolates with intermediate MIC values to clindamycin and ciprofloxacin were mostly of food and human origin and belonged to serotype 4b/4e and ST9. Regarding the time frame of isolate collection, comparing the last 3 years (2007-2009) to previous years (1998-2006), an increase was observed in the percentage of resistant and intermediate isolates per year. This trend strongly suggests the need for increasing attention on the prevalence of antimicrobial resistance in L. monocytogenes in Italy. To predict future resistance trends, the monitoring of clinical intermediate resistance might represent a useful tool especially for antibiotics associated to multiple-step mechanisms of acquired resistance. A specific focus should be addressed to antimicrobial-resistant isolates of serotype 4b, repeatedly associated with food-borne outbreaks.

Genotypic Resistance to Quinolone and Tetracycline in Salmonella Dublin Strains Isolated from Humans and Animals in Brazil.

Resistance of Salmonella Dublin strains to quinolones and tetracycline has been increasing worldwide. Studies regarding the genotypic resistance traits of strains of this serovar isolated in Brazil are scarce. This study aims to examine the genetic characteristics of Salmonella Dublin strains isolated in Brazil, which are associated with resistance to quinolone and tetracycline. The minimum inhibitory concentrations (MICs) of nalidixic acid, ciprofloxacin, and tetracycline of the 10 strains sensitive and 21 strains resistant to quinolone and tetracycline were determined using Etest.® The mutation profiles of the gyrA, gyrB, parC, and parE genes were accessed by sequencing, while the presence of plasmid-mediated quinolone resistance and tet genes was analyzed by PCR. Quinolone-resistant strains presented the amino acid substitutions Ser96→Tyr, Ser96→Phe, Asp107→Asn, or Asp108→Gly on the gyrA gene, and the Ser224→Phe and Glu231→Asp mutations on the gyrB gene. The qnrA, tet(A), and tet(B) genes were detected in 5, 13, and 6 strains, respectively. Analysis of the MIC values revealed that 1 and 3 strains presented intermediate and resistant MIC profiles to nalidixic acid, respectively; 6 strains presented intermediate MIC profile to ciprofloxacin; and 13 strains presented resistant MIC profile to tetracycline. In the Salmonella Dublin strains studied, quinolone resistance was mainly related to mutation points that led to target alteration in the gyrA and gyrB genes, while tetracycline resistance was associated with the presence of tet(A) and/or tet(B) genes, with the highest resistance levels detected in strains bearing the tet(B) gene. The presence of the aforementioned genotypic resistance traits in Salmonella Dublin strains isolated over 33 years in Brazil indicates that ciprofloxacin or tetracycline therapy against such strains may fail.

Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015.

Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted.

In vitro activity of tedizolid against Staphylococcus aureus and Streptococcus pneumoniae collected in 2013 and 2014 from sites in Latin American countries, Australia, New Zealand, and China.

Tedizolid is an oxazolidinone with an antimicrobial in vitro potency advantage against Gram-positive bacterial pathogens compared to other currently marketed drugs in this class, including linezolid. Tedizolid was compared to linezolid when tested against Staphylococcus aureus and Streptococcus pneumoniae isolates collected from countries in Latin America and the Asia-Pacific. Isolates were tested by broth microdilution susceptibility methods against tedizolid, linezolid, and non-class comparators in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The activity of tedizolid against S. aureus was potent and consistent in Latin America (MIC90, 0.5mg/L), Australia and New Zealand (MIC90, 0.25mg/L), and China (MIC90, 0.5mg/L). Based on MIC90 results, tedizolid was four- to eight-fold more active than linezolid against S. aureus, including both methicillin-susceptible and -resistant isolates. Only two tedizolid non-susceptible strains were observed; both had intermediate minimum inhibitory concentration (MIC) values of 1mg/L, for which the MICs of linezolid was higher (≥2mg/L). Tedizolid (MIC90, 0.25mg/L) was four-fold more potent than linezolid (MIC90, 1mg/L) against S. pneumoniae in all countries that provided isolates. The findings from this study support the global clinical development of tedizolid for Gram-positive infections.

Assessing the antibiotic susceptibility of freshwater Cyanobacteria spp.

Freshwater is a vehicle for the emergence and dissemination of antibiotic resistance. Cyanobacteria are ubiquitous in freshwater, where they are exposed to antibiotics and resistant organisms, but their role on water resistome was never evaluated. Data concerning the effects of antibiotics on cyanobacteria, obtained by distinct methodologies, is often contradictory. This emphasizes the importance of developing procedures to understand the trends of antibiotic susceptibility in cyanobacteria. In this study we aimed to evaluate the susceptibility of four cyanobacterial isolates from different genera (Microcystis aeruginosa, Aphanizomenon gracile, Chrisosporum bergii, Planktothix agradhii), and among them nine isolates from the same specie (M. aeruginosa) to distinct antibiotics (amoxicillin, ceftazidime, ceftriaxone, kanamycine, gentamicine, tetracycline, trimethoprim, nalidixic acid, norfloxacin). We used a method adapted from the bacteria standard broth microdilution. Cyanobacteria were exposed to serial dilution of each antibiotic (0.0015–1.6 mg/L) in Z8 medium (20 ± 1°C; 14/10 h L/D cycle; light intensity 16 ± 4 μEm−2s−1). Cell growth was followed overtime (OD450nm/microscopic examination) and the minimum inhibitory concentrations (MICs) were calculated for each antibiotic/isolate. We found that β-lactams exhibited the lower MICs, aminoglycosides, tetracycline and norfloxacine presented intermediate MICs; none of the isolates were susceptible to trimethoprim and nalidixic acid. The reduced susceptibility of all tested cyanobacteria to some antibiotics suggests that they might be naturally non-susceptible to these compounds, or that they might became non-susceptible due to antibiotic contamination pressure, or to the transfer of genes from resistant bacteria present in the environment.

Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy

Use of rifampicin (RIF) in combination with colistin (COL) has been proposed for the treatment of multidrug-resistant Acinetobacter baumannii infections owing to in vitro synergism. The aim of the present study was to evaluate the molecular epidemiology and mechanisms of RIF resistance in 57 clinical isolates of A. baumannii in two tertiary care hospitals in Naples (Italy) from 2006 to 2010. Amongst the collection, 36 isolates showed high RIF minimum inhibitory concentrations (MICs) (256 mg/L to ≥512 mg/L), 16 showed intermediate MICs (8–16 mg/L) and 5 had low MICs (4 mg/L). Of the 36 isolates with elevated RIF MICs, 35 were assigned to sequence type ST2 and 1 to ST78. Amongst the 57 isolates, 35 carried at least one mutation in rpoB, including H535L in 9 isolates and double mutations D525N and P544L in 7 isolates, whilst 22 showed no rpoB mutations. Treatment with the efflux pump inhibitor phenyl-arginine-β-naphthylamide (PAβN) of resistant isolates with no mutations in rpoB and different RIF MICs reduced the MIC by >10-fold and restored the synergism between RIF and COL in time–kill studies, whilst it had no effect on strains carrying rpoB mutations. In conclusion, the emergence of elevated RIF MICs in A. baumannii isolates from our geographical area was mostly caused by mutations in rpoB; low to intermediate RIF MICs were also caused by altered membrane permeability to the drug. The phenomenon was contributed by the selection of two prevalent clones both assigned to ST2 genotype. These data may have implications for the correct identification of cases with A. baumannii infection that would not benefit from addition of RIF to COL.

Microbial inhibitory and radical scavenging activities of cold‐pressed terpeneless Valencia orange (Citrus sinensis) oil in different dispersing agents

Due to their low solubility in water, oil-based bioactive compounds require dispersion in a surface-active agent or appropriate solvents to ensure maximum contact with microorganisms. These combinations, however, may change their physical and/or chemical characteristics and consequently alter the desired functionality. The objective of this study was to determine the impact of selected dispersing agents, ethanol, dimethyl sulfoxide (DMSO), and Tween-80, on cold-pressed terpeneless (CPT) Valencia orange oil to function as a free radical scavenger and an antimicrobial food additive. When dissolved in ethanol or DMSO, the orange oil fraction had similar minimum inhibitory concentrations (MIC) for Listeria monocytogenes ATCC 19 115 (0.3% and 0.25% v/v respectively), which were significantly lower (P <or= 0.5) than the MIC for Salmonella typhimurium ATCC 14 028 (1% v/v). Both ethanol and DMSO oil dispersion systems exhibited an intermediate MIC (0.75% v/v) for Lactobacillus plantarum WCFS1. The orange oil (up to 3%) in an aqueous solution of 0.1% Tween-80 yielded no inhibitory activities against any of the test bacteria. However, the 1% natural orange oil dispersed in Tween-80 exhibited 56.86% 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical inhibition versus 18.37% and 16.60% when the same level of orange oil was dissolved in DMSO or ethanol, respectively. At the same orange oil concentration, the oil/Tween-80 suspension yielded 57.92% neutralization of hydroxyl radicals. This represents 71.37% of the mannitol antioxidant activity, which was used as a positive control. These findings suggest that Tween-80 is an appropriate dispersing agent only if the antioxidant functionality is desired. If both antimicrobial and antioxidant properties are needed, the CPT Valencia orange oil should be dispersed in either DMSO or ethanol.

Positive selection in penicillin-binding proteins 1a, 2b, and 2x from Streptococcus pneumoniae and its correlation with amoxicillin resistance development

The efficacy of β-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs), however, this has been less so for amoxicillin than for penicillin. Recently, there have been a number of important methods developed to detect molecular adaptation in protein coding genes. The purpose of this study is to employ modern molecular selection approaches to predict sites under positive selection pressure in PBPs, derived from a large international S. pneumoniae collection of amoxicillin resistant and susceptible isolates, and encompassing a comparative data set of 354 pbp1a, 335 pbp2b, and 389 pbp2x gene sequences. A correspondence discriminant analysis (CDA) of positively selected pbp sites and amoxicillin MIC (minimum inhibitory concentration) values is then used to detect sites under positive selection pressure that are important in discriminating different amoxicillin MICs. Molecular adaptation was evident throughout PBP2X, with numerous positively selected sites in both the transpeptidase (TP) and C-terminal domains, strongly correlated with discriminating amoxicillin MICs. In the case of PBP1A positive selection was present in the glycosyltransfer (GT), TP and C-terminal domains. Sites within the TP domain tended to be correlated with the discrimination of low from intermediate MICs, whereas sites within the C-terminal tail, with a discrimination of intermediate from fully resistant. Most of the positively selected sites within PBP2B were in the N-terminal domain and were not correlated with amoxicillin MICs, however, several sites taken from the literature for the TP domain were strongly associated with discriminating high from intermediate level amoxicillin resistance. Many of the positively selected sites could be directly associated with functional inferences based on the crystal structures of these proteins. Our results suggest that clinical emphasis on TP domain sequences of these proteins may result in missing information relevant to antibiotic resistance development.

A multicenter study of the prevalence and susceptibility patterns of isolates of Streptococcus pneumoniae with reduced susceptibility to penicillin G in Louisiana.

Because of increasing reports of multiple-antibiotic-resistant strains of Streptococcus pneumoniae and associated clinical failures, this study was performed to determine the prevalence of multiresistance among strains from nine Louisiana medical centers. Using a National Committee for Laboratory Standards broth microdilution method, 481 strains were tested. Of these, 70% were penicillin-susceptible (PS), 23% had intermediate minimum inhibitory concentration values to penicillin (I), and 7% were fully resistant to penicillin (PR). The isolation rates (15% to 40% for I strains and 0% to 33% for PR strains) at the various medical centers varied appreciably. The prevalence of penicillin resistance was highest among upper respiratory isolates, while cross-resistance to other antimicrobials varied. The least cross-resistance was noted among PS strains. However, strains with reduced penicillin susceptibility had high levels of cross-resistance. Among I strains, the prevalence of cross-resistance (%) was noted for amoxicillin/clavulanate (6%), cefuroxime (71%), cefaclor (91%), ceftriaxone (13%), cefotaxime (34%), erythromycin (67%), azithromycin (32%), and clarithromycin (32%). For PR strains, the prevalence of cross-resistance was 97% for amoxicillin/clavulanate, cefuroxime, and cefaclor; 67% for ceftriaxone and erythromycin; 89% for cefotaxime; and 69% for azithromycin and clarithromycin. These data emphasize the high prevalence of multiple-antimicrobial-resistance among strains of S pneumoniae with reduced penicillin susceptibility in this geographic area.

Evolution of Staphylococcus aureus resistance to erythromycin in Denmark, 1959 to 1988: correlations between characteristics of erythromycin-resistant bacteraemia strains

In an attempt to characterize erythromycin-resistant Staphylococcus aureus we present the intricate relationships between the following factors: phage type, period of isolation, antibiogram, minimum inhibitory concentration (MIC) to erythromycin, inducible or constitutive resistance, spectinomycin susceptibility, hospital- or community-acquired infection, and mortality rate. We studied 718 cases of bacteraemia with erythromycinresistant S. aureus, occurring between 1959 and 1988. Central factors were phage type pattern, period of isolation, and antibiogram. Between 1959 and 1973 the majority of the erythromycin-resistant strains were multiresistant and belonged to the 83A complex and the related group III. They were mainly inducibly resistant, spectinomycin resistant, and had intermediate MICs (1–4 mg l −1) to erythromycin. The majority of these strains came from hospital-acquired infections and still exist today, although in decreased numbers. By contrast, erythromycin-resistant S. aureus isolated in recent years are usually co-resistant only to penicillin and more rarely also to tetracycline. These strains have inducible resistance, are spectinomycin susceptible, and have a high erythromycin MIC. They are isolated both from hospital- and community-acquired infections. Strains with constitutive resistance to macrolides occurred at a stable low level (13%) during the whole observation period and always had high MICs to erythromycin. The mortality rate among patients with S. aureus bacteraemia due to an erythromycin-resistant strain was only associated with the year of infection and decreased from 61% in the first 15-year period to 40% in the subsequent 15 years.