Expression of AraC/XylS stress response regulators in two distinct carbapenem-resistant Enterobacter cloacae ST89 biotypes.

BACKGROUND: The growing incidence of MDR Gram-negative bacteria is a rapidly emerging challenge in modern medicine. OBJECTIVES: We sought to establish the role of intrinsic drug-resistance regulators in combination with specific genetic mutations in 11 Enterobacter cloacae isolates obtained from a single patient within a 7 week period. METHODS: The molecular characterization of eight carbapenem-resistant and three carbapenem-susceptible E. cloacae ST89 isolates included expression-level analysis and WGS. Quantitative PCR included: (i) chromosomal cephalosporinase gene (ampC); (ii) membrane permeability factor genes, e.g. ompF, ompC, acrA, acrB and tolC; and (iii) intrinsic regulatory genes, e.g. ramA, ampR, rob, marA and soxS, which confer reductions in antibiotic susceptibility. RESULTS: In this study we describe the influence of the alterations in membrane permeability (ompF and ompC levels), intrinsic regulatory genes (ramA, marA, soxS) and intrinsic chromosomal cephalosporinase AmpC on reductions in carbapenem susceptibility of E. cloacae clinical isolates. Interestingly, only the first isolate possessed the acquired VIM-4 carbapenemase, which has been lost in subsequent isolates. The remaining XDR E. cloacae ST89 isolates presented complex carbapenem-resistance pathways, which included perturbations in permeability of bacterial membranes mediated by overexpression of ramA, encoding an AraC/XylS global regulator. Moreover, susceptible isolates differed significantly from other isolates in terms of marA down-regulation and soxS up-regulation. CONCLUSIONS: Molecular mechanisms of resistance among carbapenem-resistant E. cloacae included production of acquired VIM-4 carbapenemase, significant alterations in membrane permeability due to increased expression of ramA, encoding an AraC/XylS global regulator, and the overproduction of chromosomal AmpC cephalosporinase.

Emergence of Pseudomonas aeruginosa with class 1 integron carrying blaVIM-2 and blaVIM-4 in the University Clinical Hospital of Bialystok (northeastern Poland).

The effectiveness of carbapenems, considered as last-resort antimicrobials in severe infections, becomes compromised by bacterial resistance. The production of metallo-ß-lactamases (MBLs) is the most significant threat to carbapenems activity among Pseudomonas aeruginosa. The aim of this study was to assess the presence and type of MBLs genes in carbapenem-resistant P. aeruginosa clinical strains, to identify the location of MBLs genes and to determine genetic relatedness between MBL-producers using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The first identified MBL-positive (with blaVIM genes) P. aeruginosa strains were isolated from patients hospitalized in the University Clinical Hospital of Bialystok in the period from September 2012 to December 2013. Variants of MBLs genes and variable integron regions were characterized by PCR and sequencing. PFGE was performed after digesting of bacterial genomes by XbaI enzyme. By MLST seven housekeeping genes were analyzed for the determination of sequence type (ST). Three strains carried the blaVIM-2 gene and one harbored the blaVIM-4 gene. The blaVIM genes resided within class 1 integrons. PCR mapping of integrons revealed the presence of four different cassette arrays. Genetic relatedness analysis by PFGE classified VIM-positive strains into four unrelated pulsotypes (A-D). MLST demonstrated the presence of four (ST 111, ST27, and ST17) different sequence type including one previously undescribed new type of ST 2342. Antimicrobial susceptibility testing showed that VIM-positive strains were resistant to carbapenems, cephalosporins, aminoglycosides, and quinolones, intermediate to aztreonam, and susceptible only to colistin. Integrons mapping, PFGE, and MLST results may point to different origin of these strains and independent introduction into hospitalized patients.

Identification of plasmid OXA and other ß-lactamase genes among carbapenem-resistant isolates of Pseudomonas aeruginosa from the Clinical University Hospital in northeastern Poland.

The aim of the study was to evaluate the prevalence of OXA and other ß-lactamase genes, antibiotic susceptibility, and the genetic relatedness among clinical isolates of P. aeruginosa resistant to carbapenems. The presence of bla- OXA genes was demonstrated in 48% of isolates belonging to four PFGE profiles. Most of them contained the blaOXA-2 gene (88.3%). Other blaOXA genes (Ps1310 with blaOXA-30 and Ps1309 with blaOXA-10) were found in only two isolates. The tested isolates also contained other ß-lactamase genes such as blaVIM-2, blaVIM-4, blaSHV-5, and blaTEM-1. All isolates were susceptible only to colistin (100%).

In vitro activity of rifampicin alone and in combination with imipenem against multidrug-resistant Acinetobacter baumannii harboring the blaOXA-72 resistance gene.

BACKGROUND: The growing incidence of multidrug resistance (MDR) in bacteria is an emerging challenge in the treatment of infections. Acinetobacter baumannii is an opportunistic pathogen prone to exhibit MDR that contributes significantly to nosocomial infections, particularly in severely ill patients. Thus, we performed research on rifampicin activity against selected MDR OXA-72 carbapenemase-producing A. baumannii strains. Since it is widely accepted that rifampicin should not be used as monotherapy in order to avoid the rapid development of rifampicin resistance, we evaluated the efficacy of combination therapy with imipenem. METHODS: Minimal inhibitory concentrations (MICs) of both rifampicin and imipenem were determined by use of the broth microdilution method. Evaluations of the interactions between rifampicin and imipenem were performed by analysis of the fractional inhibitory concentration index (∑FIC), determined using the checkerboard titration method. RESULTS: All tested isolates showed full susceptibility to rifampicin. The checkerboard method revealed synergism in 5 isolates (29%) and an additive effect in another 5 isolates (29%); no difference was reported in the remaining 7 isolates (41%). Strains moderately resistant to imipenem (MIC ≤ 64 mg/l) tended to show synergy or additive interaction. CONCLUSIONS: We conclude that in vitro synergism or an additive interaction between rifampicin and imipenem most likely occurs in A. baumannii strains showing moderate resistance to imipenem (MIC ≤ 64 mg/l). Moreover, utilizing this combination in the therapy of infections caused by strains exhibiting higher levels of resistance (MIC > 64 mg/l) is not recommended since in this setting imipenem could not prevent the development of rifampicin resistance.

Influence of unmodified and ß-glycerophosphate cross-linked chitosan on anti-Candida activity of clotrimazole in semi-solid delivery systems.

The combination of an antifungal agent and drug carrier with adjunctive antimicrobial properties represents novel strategy of complex therapy in pharmaceutical technology. The goal of this study was to investigate the unmodified and ion cross-linked chitosan's influence on anti-Candida activity of clotrimazole used as a model drug in hydrogels. It was particularly crucial to explore whether the chitosans' structure modification by ß-glycerophosphate altered its antifungal properties. Antifungal studies (performed by plate diffusion method according to CLSI reference protocol) revealed that hydrogels obtained with chitosan/ß-glycerophosphate displayed lower anti-Candida effect, probably as a result of weakened polycationic properties of chitosan in the presence of ion cross-linker. Designed chitosan hydrogels with clotrimazole were found to be more efficient against tested Candida strains and showed more favorable drug release profile compared to commercially available product. These observations indicate that novel chitosan formulations may be considered as promising semi-solid delivery system of clotrimazole.

Molecular mechanisms of tigecycline-resistance among Enterobacterales.

The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to acquire mobile genetic elements such as plasmids, represent one of the most hazardous microorganisms. This phenomenon poses a serious threat to public health. Notably, the significance of tigecycline, a member of the antibiotic group glycylcyclines and derivative of tetracyclines has increased. Tigecycline is one of the last-resort antimicrobial drugs used to treat complicated infections caused by multidrug-resistant (MDR) bacteria, extensively drug-resistant (XDR) bacteria or even pan-drug-resistant (PDR) bacteria. The primary mechanisms of tigecycline resistance include efflux pumps' overexpression, tet genes and outer membrane porins. Efflux pumps are crucial in conferring multi-drug resistance by expelling antibiotics (such as tigecycline by direct expelling) and decreasing their concentration to sub-toxic levels. This review discusses the problem of tigecycline resistance, and provides important information for understanding the existing molecular mechanisms of tigecycline resistance in Enterobacterales. The emergence and spread of pathogens resistant to last-resort therapeutic options stands as a major global healthcare concern, especially when microorganisms are already resistant to carbapenems and/or colistin.

The effect of PAMAM dendrimers on the antibacterial activity of antibiotics with different water solubility.

Erythromycin (EM) and tobramycin (TOB) are well-known and widely used antibiotics, belonging to different therapeutic groups: macrolide and aminoglycoside, respectively. Moreover, they possess different solubility: EM is slightly soluble and TOB is freely soluble in water. It was previously demonstrated that PAMAM dendrimers enhanced the pharmacological activity of antifungal drugs by increasing their solubility. Therefore, it appears interesting to investigate the effect of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 (G2) and generation 3 (G3) on the antibacterial activity of antibiotics with different water solubility. In this study it was shown that the aqueous solubility of EM was significantly increased by PAMAM dendrimers (PAMAM-NH2 and PAMAM-OH caused about 8- and 7- fold solubility increases, respectively). However, it was indicated that despite the increase in the solubility, there was only slight influence on the antibacterial activity of EM (2- and 4-fold decreases in the MBC values of EM in the presence of PAMAM-OH G3 and PAMAM-NH2 G2 or G3 for strains of Staphylococcus aureus were noted, respectively). It was also found that there was no influence of PAMAM on the antibacterial activity of hydrophilic TOB.

Carbapenem-resistant strains from the family Enterobacteriaceae isolated in the period 2006-2011 from clinical specimens of patients treated at the university hospital in northeastern Poland.

INTRODUCTION: In recent years an alarming increase of carbapenem-resistant Enterobacteriaceae has been noticed, which creates frequent therapeutic problems, especially for patients residing in intensive care units (ICU). The aim of this study was to evaluate the prevalence of carbapenem-resistant strains of Enterobacteriaceae isolated in the years 2006-2011 at the University Hospital in Bialystok (UHB). METHODS: Based on microbiological analysis reports we conducted a retrospective study of strains resistant to carbapenems. We assigned strains to three carbapenem-resistance phenotypes, and analyzed susceptibility to antibiotics and prevalence of these strains in hospital wards and in clinical specimens collected from hospitalized patients. During a six-year period, 216 strains resistant to carbapenems were tested, which represents 0.96% of all Enterobacteriaceae (n = 22.391) isolated during this period. RESULTS: The greatest number of carbapenem-resistant strains was identified in 2011 (96 strains, 44.44%). Antibiotics that showed the highest activity against strains occurring most frequently (Klebsiella pneumoniae [n = 103] and Enterobacter cloacae [n = 85]) were tigecycline (102 [99.03%] of K. pneumoniae tested strains and 61 [100%] of E. cloacae strains were susceptible), colistin (33 [86.84%] of K. pneumoniae tested strains and 84 [100%] of E. cloacae were susceptible), and amikacin (86 [83.49%] of K. pneumoniae tested strains and 26 [30.58%] of E. cloacae strains were susceptible). CONCLUSIONS: Carbapenem resistance among Enterobacteriaceae isolates showed a trend to increase during the six-year period of study. Because infections caused by carbapenem-resistant strains are frequently life-threatening, the effective strategies to control the spreading of antibiotic resistance are necessary.

Hydrogel of ketoconazole and PAMAM dendrimers: formulation and antifungal activity.

Ketoconazole (KET), an imidazole derivative with well-known antifungal properties, is lipophilic and practically insoluble in water, therefore its clinical use has some practical disadvantages. The aim of the present study was to investigate the influence of PAMAM-NH(2) and PAMAM-OH dendrimers generation 2 and generation 3 on the solubility and antifungal activity of KET and to design and evaluate KET hydrogel with PAMAM dendrimers. It was shown that the surface charge of PAMAM dendrimers strongly affects their influence on the improvement of solubility and antifungal activity of KET. The MIC and MFC values obtained by broth dilution method indicate that PAMAM-NH(2) dendrimers significantly (up to 16-fold) increased the antifungal activity of KET against Candida strains (e.g., in culture Candida albicans 1103059/11 MIC value was 0.008 µg/mL and 0.064 µg/mL, and MFC was 2 µg/mL and 32 µg/mL for KET in 10 mg/mL solution of PAMAM-NH(2) G2 and pure KET, respectively). Antifungal activity of designed KET hydrogel with PAMAM-NH(2) dendrimers measured by the plate diffusion method was definitely higher than pure KET hydrogel and than commercial available product. It was shown that the improvement of solubility and in the consequence the higher KET release from hydrogels seems to be a very significant factor affecting antifungal activity of KET in hydrogels containing PAMAM dendrimers.

[In vitro resistance development in Acinetobacter baumannii to sulbactam and cefoperazone]. / Indukcja in vitro opornosci u Acinetobacter baumannii na sulbaktam i cefoperazon.

INTRODUCTION: Majority of nosocomial Acinetobacter baumannii strains are highly resistant to many available groups of antibiotics, causing therapy of infections the clinical challenge. The aim of study was to estimate of resistance development to sulbactam, cefoperazone and cefoperazone/sulbactam in Acinetobacter baumannii clinical strains. METHODS: Five Acinetobacter baumannii strains (Acb1, Acb2, Acb4, Acb13 and Acb25) were identified by the VITEK 2 GN card and the automatic system VITEK 2 according to the procedure and following the producer's instructions. Additionaly, the belonging of the strains to the species was confirmed by the presence of the bla(OXA-51-like) gene. Initial and after antibiotic exposure MIC values of sulbactam, cefoperazone and cefoperazone/sulbactam were determined by using a broth microdilution method. Antibiotic pressure of examined strains was performed in Mueller-Hinton broth containing 0,5x, 0,9x and 2x initial MIC of individual compounds during six-day passages and next six-day passages without antibiotic presence. The Mann-Whitney U test and Kruskal-Wallis non-prarametric Anova test were used to statistical analysis. RESULTS: Serial passaging of Acinetobacter baumannii strains in the presence of antibiotics caused permanent increasing MIC value independently of used concentrations in the majority of examined strains. The highest MIC value increase of sulbactam was found in Acb4 strain. Even after two passages this isolate changed MIC from 0.5 microg/ml to 4 microg/ml (increase about four levels of concentration). Moreover, after incubation in 0.9x MIC concentration similar observation was noted. No normalization of MIC value of sulbactam after incubation during next six passages without sulbactam was observed. In case of cefoperazone the highest levels of induction were noted in Acb1, Acb13 and Acb25 strains. In these strains, after two passages in presence of cefoperazone (2xMIC) the exceedance of minimal of growth concentration over the highest examined concentration was observed. Similar effects were observed in Acbl strain after stimulation with 0.9x and 0.5x MIC cefoperazone. Return of initial MIC values was received only after induction with 0.5 x MIC cefoperazone. In some cases, no opportunities for evaluation of resistance development was noted, because during stimulation with 2x MIC of used antibiotics concentarations, bactericidal effect was found. CONCLUSIONS: Sulbactam, cefoperazone and cefoperazone/sulbactam rapidly induce increasing of resistance in Acinetobacter baumannii clinical isolates. Statistically essential MIC increase after using higher concentration than lower was showed. This effect was particularly visible in the case of stimulation of cefoperazone/sulbactam combination.

New trends in application of the fumigation method in medical and non-medical fields.

INTRODUCTION: In the twentieth century, fumigation became a very popular method of disinfection, although in the same century many agents used as fumigants were withdrawn for ecological reasons. Fogging (fumigation) is a relatively new disinfection technology using dry fog, which behaves more like a gas and easily fills the sanitized space, reaching all surfaces in the room. The undoubted advantage of fumigation is the possibility of disinfecting difficult to clean areas. Fumigation has become particularly important in the twenty-first century due to procedures related to combating and preventing the spread of the coronavirus that causes COVID-19. OBJECTIVE: The aim of this review article is to summarize the current state of knowledge in the field of fumigation on the basis of past results of original research, taking into account new trends and possibilities of its application. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Due to the fact that fumigation is safe for apparatus, equipment, and electronics, while simultaneously enabling the highest possible bactericidal and virucidal levels, this method is widely used in various areas, both medical and non-medical. Fogging technology is used in the medical, pharmaceutical, and food industries, as well as in transportation, for air fumigation or surface disinfection in closed spaces, such as hospital and laboratory rooms, incubators, refrigerators, ships, trucks, railway containers, and aircraft, to name only a few. The most common fumigants are hydrogen peroxide and peracetic acid, and their mechanism of action is related to their oxidizing properties. SUMMARY: Hydrogen peroxide and peracetic acid are highly effective and non-toxic fumigants that can be safely used for fogging laboratory and medical equipment, pharmaceutical facilities, hospital rooms, and animal breeding rooms.

Air Disinfection-From Medical Areas to Vehicle.

Cars with air conditioning systems have become the norm, but these systems can be dangerous for human health as a result of the accumulation of different microorganisms, including pathogenic ones, causing severe allergy or inflammation problems. The novel purpose of this study is 2-fold: on the one hand, to test different disinfection agents on a new area, that is, automobile cabins, and on the other, to compare activity in the gas phase of these agents for disinfection of car air conditioning and cabin surfaces. This study shown that tested disinfectant agents dedicated for decontamination medical areas (agent based on peracetic acid and an agent containing didecyldimethylammonium chloride, 2-phenoxyethanol with cinnamaldehyde) can be successfully used for disinfection car air conditioning and cabin surfaces. Both disinfectants were examined in comparison to a commercial "ready-to-use" spray from a local supermarket dedicated to car air conditioning disinfection. Our research found that very effective agents in this regard were acid stabilized by hydrogen peroxide applied by fumigator, and a combination of didecyldimethylammonium chloride, 2-phenoxyethanol, and cinnamaldehyde applied by atomizer. Tested disinfection procedures of car air conditioning significantly influence the quality of cabin air and surfaces by reducing the amount of microorganisms. The comparison of disinfection properties studied agents in the gas phase reveal statistically significant differences between it effect for disinfection car air conditioning and cabin surfaces. Our research found that very effective agents in this regard were acid stabilized by hydrogen peroxide applied by fumigator, and a combination of didecyldimethylammonium chloride, 2-phenoxyethanol, and cinnamaldehyde applied by atomizer. Tested disinfection procedures of car air conditioning significantly influence the quality of cabin air and surfaces by reducing the amount of microorganisms.

Poly(amidoamine) dendrimers increase antifungal activity of clotrimazole.

Clotrimazole (CLO) is a local imidazolic antifungal agent. A major problem associated with the successful formulation of effective dosage forms containing CLO is its poor aqueous solubility, which presents a hindrance for the local availability of CLO and limits the effective antifungal therapy. In the present study, the effects of various concentrations of poly(amidoamine) (PAMAM) dendrimers generation 2 (G2) and generation 3 (G3) with amine (PAMAM-NH(2)) or hydroxyl surface groups (PAMAM-OH) on aqueous solubility and antifungal activity of CLO were studied. The obtained results showed that all tested PAMAM dendrimers improved the solubility of CLO and the more potent were PAMAM-NH(2) dendrimers. The increase in solubility of CLO was highest at dendrimer concentration of 10 mg/ml. Microbiology studies indicated that only PAMAM-NH(2) dendrimers significantly increased the antifungal activity of CLO (a 4-32-fold increase in the antifungal activity compared to pure CLO) and the most potent was dendrimer PAMAM-NH(2) G2. These observations indicate that PAMAM dendrimers might be considered as potential carriers of CLO and provide further impetus to evaluate these polymers for use in basic drug delivery studies and to design semisolid dosage forms based on dendrimers with antimicrobial drugs, like CLO.

Plasmid Mediated mcr-1.1 Colistin-Resistance in Clinical Extraintestinal Escherichia coli Strains Isolated in Poland.

Objectives: The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a "last-resort" antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne mcr colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal Escherichia coli strains. Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical E. coli strains. Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene. Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an "epidemic" plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.

In vitro antiproliferative and antifungal activity of essential oils from Erigeron acris L. and Erigeron annuus (L.) Pers.

Antiproliferative and antifungal activities of essential oils from Erigeron acris root and herb and from Erigeron annuus herb were investigated. The cell viability assay was performed in cultured fibroblasts, cancer cell lines (MCF-7 and MDA-MBA-231), and endometrial adenocarcinoma (Ishikawa) cells as well as colon adenocarcinoma (DLD-1) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The essential oil from E. acris root showed the highest antiproliferative activity in the MCF-7 cell line with an IC50 value of 14.5 microg/mL. No effect of the essential oil on normal cells at that concentration was found. Antifungal activity against various strains of five Candida species, i.e. C. albicans, C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis, was tested by the microdilution method. It was found that all examined oils can be useful as antifungal agents against the above-mentioned species, but the essential oil of E. acris herb was the most active. Their minimum inhibitory concentrations (MIC) ranged from 30 to 0.4 microL/mL. The data presented suggest that essential oils from E. acris and E. annuus possess antifungal activity against Candida spp. and antiproliferative activity against breast cancer MCF-7 cells.

Infection caused by Klebsiella pneumoniae ST11 in a patient after craniectomy.

Klebsiella pneumoniae infections have always been an important problem in public health, but today, the increasing resistance of these bacteria to antibiotics due to ß-lactamases production has renewed interest in K. pneumoniae infections. The aim of the study was to present a case of a neurosurgical patient with multidrug-resistant K. pneumoniae ST11 infection after craniectomy. Four K. pneumoniae isolates from various clinical materials of the patient undergone identification and susceptibility testing with the Vitek2 system. Tests for ß-lactamases production were performed according to EUCAST guidelines. Strains were analyzed for bla genes responsible for ß-lactamase production (blaTEM, blaSHV, blaCTX-M, blaVIM, blaIMP, blaNDM, blaKPC, blaOXA-48) using PCR. Moreover, the genetic relatedness of these isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All tested strain presented multidrug resistance. The highest susceptibility was observed for imipenem, meropenem, and ertapenem. The strain isolated from the nervous system was ESBL-positive with blaSHV-11, blaTEM-1, and blaCTX-M-15 genes. Additionally, the strain from urine was blaKPC-3-positive. Molecular typing revealed that all strains belonged to the same clone and identified two PFGE profiles. The analysis of MLST allelic profile showed that tested K. pneumoniae strains belonged to ST11. Identification of ST11 K. pneumoniae as etiological factor of infection unfavorably impacts on prognosis among neurosurgical patient after craniectomy.

[Asperger's disorder diagnosed in the man treated with chronic and resistant emotional and behavioral disturbances--the case report]. / Podejrzenie zespolu Aspergera u mezczyzny z przewleklymi zaburzeniami zachowania i emocji--opis przypadku.

Asperger's disorder is a nosologic phenomena, that is similar to autism, and falls under the category of pervasive developmental disorders. The unknown and probably multi-factor aetiology, wide clinical picture and not completely defined and clinically relevant diagnostic criteria are the topic of discussion between investigators and clinicians. In the article presented, a single case report of a 39-year old male patient, diagnosed and treated for years due to chronic and resistant emotional and behavioural disturbances, not clearly defined psychotic symptoms and dominating dysfunctions of social involvement, may be a voice in the debate about Asperger's disorder spectrum, comorbidity in Asperger's syndrome and serve to remind the clinicians, that pervasive developmental disorders could really be diagnosed in adults.

Activity of Ceftazidime-Avibactam Alone and in Combination with Ertapenem, Fosfomycin, and Tigecycline Against Carbapenemase-Producing Klebsiella pneumoniae.

The aim of this study was to investigate the synergy between ceftazidime-avibactam, ertapenem, fosfomycin, and tigecycline against carbapenemase-producing Klebsiella pneumoniae using the E test MIC:MIC (minimum inhibitory concentration) ratio synergy method. The results were interpreted using fractional inhibitory concentration index (FICI) to describe the effects of antimicrobial combinations in vitro. To assess the clinical significance of each antibiotic combination, the susceptible breakpoint index (SBPI) was calculated for each combination, and within each strain. The FICI method revealed that the most synergistic combinations against carbapenemase-producing K. pneumoniae were ceftazidime-avibactam with ertapenem and ceftazidime-avibactam with fosfomycin. This effect was demonstrated in 47% (9/19) of all tested clinical K. pneumoniae isolates. Considering the effects of all drug combinations in K. pneumoniae harboring blaKPC, blaNDM, and blaOXA-48 genes, we observed that the combination of ceftazidime-avibactam with fosfomycin was the most synergistic in New Delhi metallo-ß-lactamase (NDM)-producing K. pneumoniae, and the combination of ceftazidime-avibactam with ertapenem was the most synergistic in K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae. In addition, all tested combinations were synergistic against oxacillinase (OXA)-48-producing K. pneumoniae, except the combination of ceftazidime-avibactam with tigecycline. The SBPI index showed that ceftazidime-avibactam in combination with fosfomycin reduced the MIC to less than the susceptibility breakpoint among all tested carbapenemase-producing K. pneumoniae. Moreover, the combinations of ceftazidime-avibactam with ertapenem, and ceftazidime-avibactam with tigecycline were able to reduce the MIC to less than the susceptibility breakpoint in all KPC- and OXA-48-producing K. pneumoniae.

[Susceptibility of Staphylococcus aureus to new macrolide antibiotics]. / Wrazliwosc Staphylococcus aureus na nowe antybiotyki makrolidowe.

A total of 73 isolates of Staphylococcus aureus (26 - MRSA, 47 - MSSA) were tested for their susceptibility to macrolide antibiotics and new derivatives (azalide - azythromycin and ketolide -telithromycin). We observed a high - level resistance of MRSA isolates to all tested antibiotics. Over 96% of isolates were resistant to macrolides and azalides and 92,3% to ketolides. Majority of MSSA isolates (93.6%) demonstrated a high-level susceptibility to telithromycin. Mechanisms of resistance to macrolide antibiotics (34 - MLSB and 1 - MSB) were found among 47,9% Staphylococcus aureus isolates. All of MSSA (100%) and 40% MRSA isolates with induction phenotype of resistance (MLSB(I)) were sensitive to telithromycin. Isolates with constitutive phenotype of resistance (MLSB(K)) were resistant to all of the tested antibiotics.

[Vancomycin resistance among strains of Enterococcus faecium]. / Opornosc na wankomycyne wsród szczepów Enterococcus faecium.

A total of 48 clinical isolates of Enterococcus faecium were tested for their susceptibility to glycopeptide antibiotics (vancomycin and teicoplanin). We observed a low-level of resistance to vancomycin (phenotype Van B) for 4.2% isolates. MICs for these strains were MIC(vancomycin) = 8 mg/L and MIC(teicoplanin) = 0,75 mg/L. Among all of the tested strains, 66.7% were resistant to aminoglycoside antibiotics (phenotype HLAR).