High MICs Research Articles

Etiological prevalence and antifungal sensitivity patterns of dermatophytosis in India - A multicentric study.

The prevalence of dermatophytes varies with season, geographical area, socio-economic factors and effective management strategies. The aim of the study was to assess the prevalence of pathogenic dermatophytes, clinical types of dermatophyte fungal infection, and in vitro antifungal drug susceptibility testing against dermatophytes. Three hundred and ninety five patients with dermatophytosis were enrolled from five cities (Mumbai, Delhi, Lucknow, Kolkata and Hyderabad) across India. All patients were subjected to clinical examination and investigations, including potassium hydroxide microscopy, fungal culture and antifungal drug susceptibility testing. Trichophyton rubrum was the most common species identified (68.4%), followed by T. mentagrophytes (29.3%). Within species, T. mentagrophytes was prevalent in humid environmental conditions (Mumbai and Kolkata), whereas T. rubrum was prevalent in noncoastal areas (Delhi, Lucknow and Hyderabad). Tinea corporis (71.4%) and tinea cruris (62.0%) were the common clinical types observed. antifungal drug susceptibility testing data indicated that minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC-90) was lowest for griseofulvin (0.25-3.0 μg/mL). Among oral antifungals, the mean MIC of itraconazole was within the range (0.84 [0.252] μg/ mL), whereas high mean MIC values were reported for terbinafine (0.05 [0.043] μg/mL). Among topical agents, lowest mean MIC values were reported for luliconazole (0.29 [0.286] μg/mL), eberconazole (0.32 [0.251]) μg/mL and amorolfine (0.60 [0.306]) μg/mL. Lack of correlation between in vitro antifungal susceptibility and clinical outcome and absence of defined MIC breakpoints. T. rubrum was the most common, followed by T. mentagrophytes as an emerging/codominant fungal isolate in India. Tinea corporis was the most common clinical type of dermatophytosis. Mean MIC of terbinafine was above the reference range, while it was within the range for itraconazole; griseofulvin had the lowest mean MIC. Luliconazole presented the lowest mean MIC values across cities.

MALDI-TOF MS characterisation, genetic diversity and antifungal susceptibility of Trichosporon species from Iranian clinical samples.

Trichosporonosis is an emerging fungal infection caused by Trichosporon species, a genus of yeast-like fungi, which are frequently encountered in human infections ranging from mild cutaneous lesions to fungemia in immunocompromised patients. The incidence of trichosporonosis has increased in recent years, owing to higher numbers of individuals at risk for this infection. Although amphotericin B, posaconazole and isavuconazole are generally effective against Trichosporon species, some isolates may have variable susceptibility to these antifungals. Herein, we evaluated the species distribution, genetic diversity and antifungal susceptibility profiles of Trichosporon isolates in Iran. The yeasts were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Phylogenetic analysis was performed based on amplified fragment length polymorphism (AFLP). The in vitro susceptibilities of eight antifungal agents were analysed using the Clinical and Laboratory Standards Institute broth microdilution methods. The isolates belonged to the species Tasahii (n=20), Tjaponicum (n=4) and Tfaecale (n=3). A dendrogram of the AFLP analysis demonstrated that Tasahii and non-asahii Trichosporon strains (Tjaponicum and Tfaecale) are phylogenetically distinct. While voriconazole was the most active agent (GM MIC=0.075μg/ml), high fluconazole MICs (8μg/ml) were observed for a quarter of Trichosporon isolates. The GM MIC value of amphotericin B for Tasahii and non-asahii Trichosporon species was 0.9μg/ml. The distribution and antifungal susceptibility patterns of the identified Trichosporon species could inform therapeutic choices for treating these emerging life-threatening fungi.

Antibacterial activity of Lippia alba, Myrcia lundianaand Ocimum basilicumessential oils against six food-spoiling pathogenic microorganisms

The aim of this study was to undertake a screening experiment on essential oils (EO) of Myrcia lundiana, Ocimum basilicum and Lippia alba against six food-spoiling pathogenic bacteria. Seventy-two (72) samples were initially analyzed for antimicrobial activity based on the agar diffusion test. The minimum inhibitory (MIC) and bactericidal (MBC) concentrations were determined for the 12 samples which showed greatest antimicrobial potential in this stage. Two samples of L. alba, three samples of M. lundiana and seven samples of O. basilicum showed a MIC of 0.12-125 μL/mL for the six tested bacteria. Of these, the EO of O. basilicum cultivar Maria Bonita stood out with the lowest MIC and MBC. Thus, a mixture simulating this essential oil was prepared from commercial standards of the compounds (±)-linalool, geraniol and 1,8-cineole. Significantly higher MIC and MBC were detected in the simulation compared to the respective EO, suggesting a synergistic effectbetween compounds.

Evaluation of DermaGenius® resistance real-time polymerase chain reaction for rapid detection of terbinafine-resistant Trichophyton species.

Treatment-resistant dermatophytosis caused by Trichophyton mentagrophytes/interdigitale complex has emerged as a global public health threat, particularly in endemic countries like India and has spread to many other countries. This veritable spread is alarming due to increase in resistance to terbinafine, which targets the ergosterol biosynthetic pathway by inhibiting the enzyme squalene epoxidase (SQLE). About two third of studies worldwide have reported amino acid substitutions Phe397Leu and Leu393Phe in the SQLE protein to be responsible for high terbinafine MICs. We evaluated the efficacy of the newly developed DermaGenius® Resistance real-time PCR assay to rapidly identify Trichophyton isolates harbouring most common SQLE mutant (Phe397Leu and Leu393Phe) conferring high terbinafine resistance from wild-type susceptible isolates. A total of 97 Trichophyton isolates confirmed by ITS sequencing as T.mentagrophytes/interdigitale (recently named T.indotineae n=90), T.rubrum/T.soudanense (n=3), T mentagrophytes (n=2) and T tonsurans (n=2) were analysed to evaluate DermaGenius® Resistance real-time PCR assay. All 40 T.indotineae isolates exhibiting amino acid substitutions Phe397Leu or Leu393Phe identified by SQLE gene sequencing were evaluated for detection of non-wild-type strains by real-time PCR. Antifungal susceptibility testing for terbinafine was done by CLSI microbroth dilution method. All terbinafine-resistant isolates harbouring amino acid substitutions Phe397Leu or Leu393Phe in SQLE gene were correctly recorded as SQLE mutants by the DermaGenius® Resistance real-time PCR assay. The DermaGenius® Resistance real-time PCR assay effectively identified Trichophyton species and distinguished wild-type from SQLE mutant genotype that harbour Phe397Leu and Leu393Phe amino acid substitutions.

Virulence genes and sanitizers resistance in Salmonella isolates from eggs in southern Brazil.

Salmonellaspp. causes foodborne diseases related to the consumption of contaminated foods, especially poultry products. This study aimed to investigate the occurrence of Salmonella spp. serovars in raw eggs from supermarkets and street food markets in southern Brazil, to analyze virulence genes, resistance profiling to antimicrobials and sanitizers, and to determine the susceptibility of the isolates to Butia odorata extract. Among 160 samples analyzed, just two (1.25%) were positive for Salmonella spp.. One positive sample was from egg yolk (S. enterica serovar Gallinarum, isolate S28), and another one was from eggshell (S. enterica serovar Panama, isolate S37). Regarding the virulence genes, the isolate S37 harbored all the genes evaluated (hilA, invA, spvC, sefA, and pefA), while the isolate S28 did not harbor the pefA gene. The isolate S28 was resistant to tobramycin, azithromycin, and trimethoprim, while the isolate S37 showed resistance profile just to nalidixic acid. However, none of the resistance genes evaluated were identified. Both isolates showed resistance to benzalkonium chloride, chlorhexidine digluconate, sodium hypochlorite, and peracetic acid, presenting high MIC values for these sanitizers. In contrast, B. odorata extract showed antimicrobial activity against the isolates S28 and S37, however, more studies are needed to prove its potential as a natural antimicrobial compound.

Molecular identification and antifungal susceptibility profiles of Candida dubliniensis and Candida africana isolated from vulvovaginal candidiasis: A single-centre experience in Iran.

BackgroundVulvovaginal candidiasis (VVC) is a common and debilitating long‐term illness affecting million women worldwide. This disease is caused mainly by Candida albicans and a lesser extent by other species, including the two phylogenetically closely related pathogens Candida africana and Candida dubliniensis.ObjectivesIn this study, we report detailed molecular epidemiological data about the occurrence of these two pathogenic yeasts in Iranian patients affected by VVC, or its chronic recurrent form (RVVC), and provide, for the first time, data on the antifungal activity of two new drugs, efinaconazole (EFN) and luliconazole (LUL).MethodsA total of 133 vaginal yeast isolates, presumptively identified as C albicans by phenotypic and restriction analysis of rDNA, were further analysed by using a specific molecular method targeting the HWP1 gene. All C africana and C dubliniensis isolates were also tested for their in vitro susceptibility to a panel of modern and classical antifungal drugs.Results and ConclusionsBased on the molecular results, among 133 germ‐tube positive isolates, we identify 119 C albicans (89.47%), 11 C africana (8.27%) and 3 C dubliniensis (2.26%) isolates. C africana and C dubliniensis showed low MIC values for most of the antifungal drugs tested, especially for EFN and LUL, which exhibited a remarkable antifungal activity. High MIC values were observed only for nystatin and terbinafine. Although C albicans remains the most common Candida species recovered from Iranian VVC/RVVC patients, our data show that its prevalence may be slightly overestimated due to the presence of difficult‐to‐identify closely related yeast, especially C africana.

Utilization of agro-industrial waste for biosurfactant production under submerged fermentation and its synergistic application in biosorption of Pb2+

The biosurfactant production process was optimized using raw orange peel extract (ST reduction = 33.04 dyne cm−1; biosurfactant yield = ~3.7 g L−1) and the extracted metabolite was characterized in terms of its nature, and class/family. To the best of our knowledge, a first report utilizing biowaste as a sole carbon substrate for simultaneous biosurfactant production and Pb2+ removal under submerged fermentation by Bacillus haynesii strain E1. The results depicted the extracted biosurfactant to be of lipopeptide nature belonging to surfactin family having 50 mg L−1 of CMC. The crude biosurfactant was found to be tensioactive at temperature 70 °C, 6% salt concentration, and varying pH range. The biosurfactant-producing bacterium effectively remediated Pb2+ (high MIC = 2200 mg L−1) with a maximum adsorption capacity of 196.08 mg g−1. The biosorption mechanism followed Langmuir (R2 = 0.9724) and Pseudo second-order adsorption kinetics (R2 = 0.9996; 200 mg L−1).

Helicobacter cinaedi bacteraemia secondary to enterocolitis in an immunocompetent patient

BackgroundHelicobacter cinaedi are motile, gram-negative spiral rods with a natural reservoir in the intestinal tract of hamsters and rhesus monkeys. In humans, H. cinaedi has been reported in different human infections like fever, abdominal pain, gastroenteritis, proctitis, diarrhoea, erysipelas, cellulitis, arthritis, and neonatal meningitis typically diagnosed by positive blood cultures. Even though H. cinaedi has been detected from human blood and stool the entry of H. cinaedi into the blood stream was undocumented until quite recently. The use of pulse-field gel electrophoresis (PFGE) demonstrated that stool- and blood-derived H. cinaedi strains were consistent.Case presentationHere, we describe a rare Danish case of H. cinaedi bacteraemia in an immunocompetent 44-year-old male with diarrhoea. We isolated H. cinaedi from a blood culture taken at admission, and from a FecalSwab taken at day six despite ongoing antibiotic therapy. Next, we made a genetic comparison of both isolates by use of Multi-locus sequence typing (MLST)- and Single nucleotide polymorphism (SNP)-analysis. The two isolates were identical with zero SNPs and by use of MLST the isolate was identified as a novel ST20, confirming previous data of the intestinal tract as a route of H. cinaedi bacteraemia. The results of our AST showed a resistance pattern with higher MICs for ciprofloxacin and clarithromycin than for ampicillin, amoxicillin, gentamicin, and imipenem. The patient was cured with targeted therapy with pivampicillin; however, the primary source of transmission was unknown.ConclusionsIn conclusion, this case of H. cinaedi bacteraemia secondary to enterocolitis in an immunocompetent patient provide clear evidence that one route of infection occurs through translocation from the intestinal tract to the bloodstream. Helicobacter cinaedi from blood and faeces were identical with a novel ST20, resistant to ciprofloxacin and clarithromycin however, the patient was cured with oral pivampicillin.

Failure of Vitek2 to reliably detect vanB-mediated vancomycin resistance in Enterococcus faecium.

The increasing prevalence of VRE necessitates their reliable detection, especially for low-level resistance mediated by vanB in Enterococcus faecium. In this prospective study we analysed if vanB-mediated vancomycin resistance can be reliably detected by Vitek2. One thousand, three hundred and forty-four enterococcal isolates from routine clinical specimens were tested by Vitek2 (bioMérieux, Nürtingen, Germany). Additionally, a bacterial suspension (with a turbidity equivalent to that of a 0.5 McFarland standard) was inoculated on chromID VRE screening agar (bioMérieux) and incubated for 48 h. If vancomycin tested susceptible by Vitek2 but growth was detected on the screening agar, PCR for vanA/vanB was performed (GeneXpert vanA/B test, Cepheid, Frankfurt, Germany). For isolates that tested susceptible to vancomycin by Vitek2 but were vanA/B positive, MICs were determined before and after cultivation in broth with increasing concentrations of vancomycin. One hundred and fifty-six out of 491 E. faecium were VRE and were predominantly vanB positive (81.0%). Of these, Vitek2 did not identify 14 as VRE (sensitivity 91.0%). By broth microdilution 9/14 isolates demonstrated high MICs (≥32 mg/L) and 5/14 showed low vancomycin MICs, which did not increase despite vancomycin exposure. Three of the 14 isolates demonstrated growth on chromID VRE; after vancomycin exposure seven additional isolates were able to grow on chromID VRE. Vitek2 fails to detect vanB-mediated vancomycin resistance consistently, especially, but not limited to, low-level resistance. As this may lead to treatment failure and further dissemination of vanB VRE, additional methods (e.g. culture on VRE screening agar or PCR) are necessary to reliably identify vanB-positive enterococci in clinical routine.

Infections due to Rare Cryptococcus Species. A Literature Review.

Infections due to rare Cryptococcus species (other than C. neoformans species complex, C. gattii species complex, C. albidus or C. laurentii) are barely reported. The aim of this work is to present a comprehensive literature review of all the papers describing infections due to these species referenced in the main databases (PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar). Clinical and epidemiological data together with laboratory findings (identification and antifungal susceptibility) of each isolate were analyzed. Fifty-eight cryptococosis due to rare species were described in 46 papers between 1934–2018. These reports included 16 rare Cryptococcus spp. that were generally associated with nervous system infections and fungemias. Some species are non-capsulated and are not able to grow at 37 °C. Few species were identified by commercially available methods, making internal transcriber spacer (ITS) and D1/D2 regions sequencing mandatory. The most potent antifungal was amphotericin B (although some species showed high MIC values). The studied strains showed high MICs values to 5-fluorocytosine (all >64 µg/mL), echinocandins (all >8 µg/mL), and fluconazole (>80% of the MICs >4 µg/mL). Due to the scarcity of the data and the absence of guidelines for the treatment of these infections, this review could be informative and could help in the diagnosis and treatment of these infections.

Antibacterial and synergistic activity of 6β-hydroxy-3-oxolup-20(29)-en-28-oic acid (6β-hydroxy betunolic acid) isolated from Schumacheria castaneifolia vahl

Multi- drug resistant microbial pathogens are a serious global health problem and thus new antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. Hence, the objective of the present study was to investigate the antibacterial activity of 6β-hydroxy-3-oxolup-20(29)-en-28-oic acid (6β-hydroxy betunolic acid) isolated from the bark of Schumacheria castaneifolia and its effect when combined with oxacillin. Antibacterial potential of 6β-hydroxy betunolic acid alone was performed using broth micro dilution assay against sixteen bacterial strains which included eight standard strains [Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), carbapenemase producing Kebsiella pneumonia (ATCC BAA 1705), carbapenemase non-producing K. pneumonia (ATCC BAA 1706) and Pseudomonas aeruginosa (ATCC 27853)] and four strains each of clinically isolated meropenem resistant Acinetobactor sp. and methicillin resistant S. aureus (MRSA) which were included in the urgent threat list and serious threat list, respectively in 2019 by the Centers for Disease Control and Prevention in the United States. Its effect when combined with oxacillin was tested against S. aureus (ATCC 29213) and MRSAs using a checkerboard dilution method. The results indicated that 6β-hydroxy betunolic acid had antibacterial activity against the tested Gram positive organisms with MICs ranging from 16 to 32 mg L−1 (MIC of oxacillin and meropenem ranged from 0.25–16 and 0.03–128 mg L−1 respectively). The high MIC values (>1024 mg L−1) of 6β-hydroxy betunolic acid against Gram negative strains indicated a likely lack of activity. Further, 6β-hydroxy betunolic acid exhibited synergistic effect with oxacillin against Staphylococcus aureus (0.49) and showed an additive effect against all the tested MRSAs. The present study suggested that the antibacterial activity of the 6β-hydroxy betunolic acid is restricted to Staphylococcus isolates and possibly Enterococcus faecalis. Further testing on different types of Gram positives and identification of the exact mechanism of action would be of importance.

In vitro activity of plazomicin against quinolone-resistant gram-negative bacteria isolated from catheter-associated urinary tract infections

Quinolone resistance among uropathogens is an increasing concern. Plazomicin is a new aminoglycoside that shows promising results against resistant bacteria. However, no study has yet tested its effect specifically on quinolone-resistant organisms. This study aimed to evaluate the in vitro activity of plazomicin and comparator drugs against quinolone-resistant Gram-negative isolates of catheter-associated urinary tract infections (CAUTI). Plazomicin demonstrated high inhibiting activity against Enterobacteriaceae isolates (95.9% at MIC≤ 2 mg/L), with MIC50/90 was 1/2 mg/L. High MICs values were detected against non-Enterobacteriaceae isolates (MIC50/90, 4/32 mg/L). Plazomicin had susceptibility rate of 97.2% against Enterobacteriaceae isolates carrying aminoglycosides modifying enzymes (AME) genes, while other aminoglycosides, amikacin and gentamicin showed reduced activity (32.4% and 25.4%, respectively). In conclusion, plazomicin showed potent in vitro activity against quinolone-resistant Enterobacteriaceae causing CAUTI, regardless of the AME pattern.

Epidemiological Characterization of Colistin and Carbapenem Resistant Enterobacteriaceae in a Tertiary: A Hospital from Anhui Province.

PurposeAntimicrobial resistance, especially carbapenem resistance Enterobacteriaceae and plasmid mediated mobile colistin resistance, is a serious issue worldwide. This study was designed to determine the epidemiological characteristics of plasmid mediated colistin resistance and carbapenem resistant Enterobacteriaceae from tertiary A hospital located in Hefei, China.MethodsTotally, 158 carbapenems resistant Enterobacteriaceae (CRE) were screened for antibiotic susceptibility, mcr-1, extended spectrum β-lactamases (ESBLs), metallo-β-lactamases (MBLs), and fosfomycin resistance genes using PCR and sequencing. The sequence types were identified by multilocus sequence typing (MLST). Plasmid profiles were determined by PCR based replicon typing (PBRT), and the plasmid sizes were confirmed by southern blotting.ResultsThe isolates showed high MIC50 and MIC90 for all antimicrobials, except tigecycline, meropenem, and colistin. The main Carbapenemase genes were blaKPC-2 (90.5%), blaNDM-1(3.7%), blaOXA-48(5.6%) and fosA3 (14.5%). The blaCTXM-15 found 36.7%, mcr-1 (3.7%) recorded in six isolates. PBRT revealed blaKPC-2 in K. pneumoniae on IncR, IncFII, and IncA/C. blaNDM-1 in E. coli on IncFII, whereas in E. cloacae noticed on IncHI2 plasmid. mcr-1 was recorded among IncFIIK, IncFII, and IncF in E. coli, K. pneumoniae, and E. cloacae. Resistance genes (mcr-1, blaNDM-1, blaKPC-2) harboring plasmids are successfully trans-conjugant to EC-600. A high incidence of ST11 was observed in K. pneumoniae carbapenem resistant isolates. While in E. coli, multiple STs were identified. However, mcr-1 in ST23 was identified for the first time in Anhui Province. Among Enterobacter cloacae, ST270 detected carrying blaNDM-1. Southern-hybridization confirmed the plasmid sizes 35–150kb.ConclusionThis study indicates the co-carrying of mcr-1, blaKPC-2, and blaNDM-1 among clinical isolates, the prevalence of different Enterobacteriaceae STs is alarming, especially in E. coli. Holding such a resistance profile is a threat for humans and animals, which may be transferred between the strains through plasmid transfusion. Persistent control actions are immediately necessary to combat this hazard.

Species identification and antifungal susceptibility testing of Aspergillus strains isolated from patients with otomycosis in northern China

There are limited studies on species distribution and susceptibility profiles of Aspergillus strains isolated from patients with otomycosis in China. A total of 69 confirmed Aspergillus species isolates were obtained from ear swabs of patients diagnosed with otomycosis from 2017 to 2018 in northern China. Identification of these Aspergillus isolates at the species level was performed using conventional morphological methods and MALDI-TOF MS in combination with molecular sequencing, and invitro susceptibility to nine antifungal agents was evaluated using the Sensititre YeastOne system. The Aspergillus section Nigri had the greatest distribution of Aspergillus isolates. A. welwitschiae (n=25) was the most predominant isolate in section Nigri, followed by A. tubingensis (n=12) and A. niger (n=11). Other Aspergillus species were also isolated, including A. terreus (n=11), A. flavus/A. oryzae (n=8), and A. fumigatus (n=2). Amphotericin B, posaconazole, and echinocandins were highly invitro active against all the isolates tested. 2.9% (2/69) of the isolates were resistant to azoles in our study, including one A. niger isolate with a high MIC value for itraconazole (ITR) (16mg/L) and one A. tubingensis isolate cross-resistant to both voriconazole (VOR) (MIC >8mg/L) and ITR (MIC >16mg/L). One A. welwitschiae and one A. niger isolate both had increased MIC values of 4mg/L against VOR. A. welwitschiae was the most prevalent Aspergillus species isolated from patients with otomycosis. Our findings also indicated that the azole-resistant Aspergillus section Nigri should be utilized to guide clinical medication for Otomycosis.

Antimicrobial Susceptibility Patterns in Neisseria gonorrhoeae Isolated from South African Pregnant Women

Background. Neisseria gonorrhoeae, a sexually transmitted infection, is associated with adverse pregnancy and neonatal outcomes. Emerging resistance towards various antibiotics has been observed globally. However, there is a lack of data on antimicrobial susceptibility patterns in N. gonorrhoeae isolated from pregnant women in our setting. This study fills in this gap in the literature. Methods. The study population included pregnant women, recruited from the antenatal clinic of the King Edward VIII hospital (KEH) in Durban. Endocervical swabs were obtained from 307 women. The swab was placed in Amies Charcoal media for culture assessments. Pure isolates of N. gonorrhoeae were subjected to antimicrobial susceptibility testing using the Etest™ method. The MIC values were assessed in accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST, 2019) breakpoints. Results. The prevalence of N. gonorrhoeae by culture was 1.9%. High MIC values to penicillin G (12-64 mg/L) indicating a resistant phenotype were observed for all isolates tested, with 50% of the isolates displaying complete resistance. Isolates with intermediate (1 mg/L) and resistance (1.9-32 mg/L) profiles to tetracycline were observed. Resistance to ciprofloxacin (1.16-3 mg/L) was also observed. Isolates displayed either dual or triple resistance to penicillin G, tetracycline, or ciprofloxacin. All isolates showed susceptibility to spectinomycin (>64 mg/L), azithromycin (1 mg/L), ceftriaxone (>0.125 mg/L), and cefixime (>0.125 mg/L). Conclusion. Despite lack of resistance to ceftriaxone and azithromycin, continuous surveillance for emerging patterns of resistance to these antibiotics is needed since they form part of the treatment guidelines.

#9: Frequency and Antimicrobial Susceptibility of Gram-Negative Organisms Causing Bloodstream Infections in Pediatric Patients from United States (US) Medical Centers (2014–2018)

Abstract Background Ceftazidime–avibactam is US FDA approved for the treatment of pneumonia and complicated intra-abdominal and urinary tract infections in adults, and it is in late-stage clinical development for the treatment of pediatric patients. Methods Organisms were consecutively collected from pediatric patients (≤17 years old) with bloodstream infections in 33 US medical centers in 2014–2018. Enterobacterales, P. aeruginosa, and H. influenzae isolates (n = 976) were susceptibility (S) tested against ceftazidime–avibactam and comparators by reference broth microdilution methods; 42.9% of isolates tested were from patients <1 year old, and 70.7% from patients ≤5 years old. Isolates with an ESBL–phenotype were screened for β-lactamase genes. Results Overall, 40.1% of organisms were Gram-negative bacteria (GNB), 57.0% Gram-positives, and 2.8% Candida spp. The five most common GNB were E. coli (32.4% of GNB), K. pneumoniae (17.3%), E. cloacae (9.8%), P. aeruginosa (9.2%), and S. marcescens (5.5%; Table). Enterobacterales, P. aeruginosa, and H. influenzae isolates combined represented 89% of GNB and all isolates (100.0%) were susceptible to ceftazidime–avibactam. Among Enterobacterales (n = 845; MIC50/90, 0.12/0.25 mg/L), the highest ceftazidime–avibactam MIC value was only 4 mg/L and 99.2% of isolates were inhibited at ≤1 mg/L. Enterobacterales susceptibility to ceftriaxone, piperacillin–tazobactam, ceftolozane–tazobactam, and meropenem were 88.2%, 93.1%, 97.5%, and 99.5%, respectively. Forty-four Enterobacterales isolates (5.2%) produced an ESBL, including CTX-M-type (n = 35 [79.5% of ESBL producers], 21 being CTX-M-15), SHV-type (12; 27.3%), and OXA-1/30 (9; 20.5%). Twelve isolates (27.3%) produced >1 ESBL. No carbapenemase gene was detected. Among ESBL producers, highest ceftazidime–avibactam MIC was 2 mg/L, and susceptibility rates for ceftolozane–tazobactam and meropenem were 92.9% and 100.0%, respectively. Ceftazidime–avibactam exhibited complete activity against P. aeruginosa (MIC50/90, 2/4 mg/L; 100.0% susceptible). P. aeruginosa susceptibility rates for meropenem, piperacillin–tazobactam, and ceftolozane–tazobactam were 82.5%, 85.6%, and 100.0%, respectively; and 10.3% of isolates exhibited multidrug-resistance phenotype (not susceptible to ≥3 classes). Ceftazidime–avibactam was highly active against H. influenzae (n = 34; MIC50/90, ≤0.015/0.03 mg/L; highest MIC, 0.06 m/L). Conclusions Ceftazidime–avibactam exhibited potent activity against a large collection of GNB isolated from pediatric patients with bacteremia and showed complete coverage (100.0% susceptibility) against P. aeruginosa, Enterobacterales, and H. influenzae.

Molecular Identification and Antifungal Susceptibility of Yeasts and Molds Isolated from Patients with Otomycosis.

Fungal otitis externa, an infection of the external auditory canal caused by molds and yeasts, accounts for approximately 10-20% of ear canal infections accompanying high recurrence. The purpose of the current study was to assess the pattern of etiological agents of otomycosis and resistance profile as well as the rate of tympanic membrane perforation. A total of 1040 patients with symptoms of fungal otitis externa, in a period of two years, were investigated. The mycological tests revealed the presence of different fungi in 237 ears (22.8%). Fungal otitis was more related to filamentous fungi of the species Aspergillus flavus (54.43%), A. tubingensis (10.97%), and A. niger (8.86%), followed by yeasts, Candida orthopsilosis (7.59%), C. albicans (6.75%), and C. parapsilosis (5.06%). Tympanic membrane perforation rate was found to be 6.75% and was more common with otomycosis caused by A. flavus, A. tubingensis and C. albicans. In antifungal susceptibility tests, all tested drugs showed generally good activity against most isolates of molds and yeasts, while tolnaftate, clotrimazole, nystatin, and terbinafine had lowest effects. We found that among Aspergillus isolates, one A. niger isolate was resistant to voriconazole, and one A. flavus isolate was resistant to amphotericin B. Furthermore, among Candida species, three isolates of C. orthopsilosis showed high MIC values to fluconazole, two C. albicans isolates were considered fluconazole resistant and one isolate of C. parapsilosis was resistant to caspofungin and 3 isolates were resistant to fluconazole. Regarding the existence of the cases with perforated tympanic membrane and emerging species causing fungal otitis in the current report, the importance of the early physical examination, precise molecular identification, and the antifungal susceptibility evaluation is highlighted.

Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A two-center pilot study

BackgroundDue to high pharmacokinetic variability, standard doses of meropenem are frequently inadequate in septic patients. Therapeutic drug monitoring of meropenem is not widely available; therefore, improved empiric dosing recommendations are needed. ObjectivesThis study aimed to compare the attainment of pharmacologic targets for two common empirical dosing regimens for meropenem in patients with septic shock. MethodsTwo empiric dosing schemes for meropenem were compared using extended infusions (120 minutes) in 32 patients with septic shock in the intensive care units at two different hospitals. One regimen was 3 × 2 g meropenem/24 h for two days, followed by 3 × 1 g meropenem/24 h; the other regimen was 4 × 1 g meropenem/24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the free drug concentration was above various target MICs for each regimen (%fT>MIC). ResultsBoth regimens led to a sufficiently high %fT>MIC for pathogens with target MICs < 4 mg/L. When higher MICs were targeted, the %fT>MIC of 4 × 1 g meropenem decreased faster than that of 3 × 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide appropriate drug concentrations. Renal function was a significant covariate of target attainment. ConclusionsThe results of this study can guide clinicians in their choice of an empirical dosing regimen for meropenem. If pathogens with low MICs (< 4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant strains require higher doses.

Expect the unexpected: fungemia caused by uncommon Candida species in a Turkish University Hospital.

Fungemia caused by uncommon Candida species (UCS) (other than C.albicans, C.glabrata, C.parapsilosis, C.tropicalis, C.krusei) is a rare but emerging threat with their potential to exhibit reduced susceptibility or resistance to antifungal agents. We identified 25 patients with UCS fungemia (9 C.kefyr, 8 C.lusitaniae, 4 C.dubliniensis, 2 C.guilliermondii, 1 C.pelliculosa, 1 C.rugosa) through January 2011 and August 2018. Echinocandins were the most common administered agents, followed by fluconazole. Overall mortality was 44%. Echinocandins and voriconazole showed sufficient activity against all tested isolates. High fluconazole MICs among C.guilliermondii, C.pelliculosa, and C.rugosa were determined. MIC value of C.pelliculosa was above the epidemiological cut-off proposed for fluconazole.

What's left in the cupboard? Older antimicrobials for treating gonorrhoea.

Neisseria gonorrhoeae has developed resistance to all antimicrobials used to treat gonorrhoea, with even ceftriaxone being undermined. It is therefore important to examine any potential to redeploy older antimicrobials routinely used for other infections to treat ceftriaxone-resistant gonococcal infections. We examined the susceptibility of N. gonorrhoeae to aztreonam, chloramphenicol, co-trimoxazole, fosfomycin, piperacillin/tazobactam and rifampicin. N. gonorrhoeae isolates (n = 94) were selected to include a range of antimicrobial susceptibilities: 58 were collected in the Gonococcal Resistance to Antimicrobials Surveillance Programme; 17 were clinical isolates referred to the PHE reference laboratory; and 19 were control strains. MICs were determined by agar dilution for the six study antimicrobials and for ceftriaxone and azithromycin as comparators. There was correlation between piperacillin/tazobactam and ceftriaxone MICs, but all five isolates with high ceftriaxone MICs (>0.5 mg/L) were inhibited by piperacillin/tazobactam at 0.06-0.5 mg/L. Aztreonam MICs for ceftriaxone-resistant isolates exceeded those of ceftriaxone. Among non-β-lactams, fosfomycin and co-trimoxazole had low, tightly clustered MICs, suggesting widespread susceptibility, rifampicin split the collection into highly susceptible and highly resistant groups and chloramphenicol had a wide MIC distribution. Although unsuitable for empirical use, piperacillin/tazobactam, fosfomycin, co-trimoxazole, rifampicin and, possibly, chloramphenicol could be considered for individual patients with ceftriaxone-resistant gonococcal infection once MICs are known. Wider surveillance of the susceptibility of N. gonorrhoeae to these agents is needed, along with clinical trials and the establishment of clinical breakpoints for N gonorrhoeae.