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Pharmacotherapy protocols used in cancer treatment are far from curative for many patients due to reasons such as drug-related toxicity and decreased effectiveness of the drug. Multidrug resistance is a defense mechanism developed by the cancer cell against different drug groups or drug combinations. One of the most important reasons is the increase in the efficiency or number of ABC transporters that ensure drug removal from the cell. Imidazopyridines, which are incorporated into the structure of many biomolecules, have been produced under laboratory conditions for many years. Imidazopyridines are effective anticancer agents that can kill cancer cells in various ways. In this review, we presented a detailed summary of studies in which imidazopyridines were used to overcome multidrug resistance by targeting ABC transporters in cancer cells. For this purpose, we collectively evaluated the synthesis strategies and laboratory results of the agents synthesized and used as drugs and the compounds whose clinical trials have not yet started. The introduction of several imidazopyridine derivatives as prescription drugs reflects the potential of these molecules. We think that agents that can provide targeted therapy will be used more frequently in the clinic and will improve treatment success. [ABSTRACT FROM AUTHOR]

Copyright of Bosphorus Medical Journal / Boğaziçi Tıp Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Van Health Sciences Journal / Van Sağlık Bilimleri Dergisi is the property of Van Yuzuncu Yil University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of ANKEM Antibiyotik & Kemoterapi Dergisi is the property of ANKEM Antibiyotik & Kemoterapi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Multidrug resistance (MDR) in gram-negative neonatal infections is difficult to manage, and the risk factors differ among different studies. Therefore, we aim to investigate the demographics, mortality, MDR status of gram-negative isolates, and risk factors for MDR gram-negative infections. Methods: We conducted a retrospective single-center study about MDR gram-negative infections in neonates between January 2012-January 2022 at Duzce University Hospital in Turkey. This study evaluates neonates with MDR gram-negative infections' risk factors and clinical features. All analyses were performed using IBM SPSS V23. In addition, univariate analyses and multivariate logistic regression models were studied to determine MDR's risk factors. Results: Of 107 gram-negative bacteria, 41 (38.3%) accounted for Enterobacter, 30 (28%) for Klebsiella pneumonia, and 22 (20.6%) for Escherichia coli. Additionally, 61 (56.5%) were MDR microorganisms. Among the susceptibility tests performed for selected isolates, 41 (77.4%) had resistance to piperacillin, 57 (75%) showed resistance to amoxiclav, and 16 (72.7%) had cefoxitin resistance. In addition, carbapenemase resistance was found in 24 (43.6%) and meropenem resistance in 13 (36.1%). Colistin, aztreonam, and tigecycline resistances were the least frequent. In addition, the following dependent risk factors increased the multidrug resistance risk in gram-negative infections; late-onset sepsis 3.547 fold (p=0.005), use of mechanical ventilation 3.143 fold (p=0.007), blood transfusion 3.587 fold (p=0.013), bronchopulmonary dysplasia 6.702 fold, (p= 0.015) and total parenteral nutrition 5.591 fold (p=0.001), lower gestational age 1.122 (1/0.891) fold (p=0.026), and birth weight 1.001 (1/0.999) fold, (p=0.013). Similarly, antibiotherapy duration was significantly higher in the MDR group than in the non-MDR group. Conclusions: The reported risk factors for MDR in gram-negative neonatal infections are all dependent risk factors. Hence clinicians must be alert to all potential risk factors. [ABSTRACT FROM AUTHOR]

Copyright of Anatolian Clinic Journal of Medical Sciences is the property of Hayat Saglik ve Sosyal Hizmetler Vakfi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Infections caused by antibiotic-resistant pathogens pose a major threat worldwide. There is an urgent need to develop effective strategies to solve this problem. The antibacterial activity of adult mesenchymal stem cells (MSCs) has recently been determined against various bacterial isolates. New approaches, such as Toll-like receptor activation, were used to enhance their antibacterial potency. This study examines the antibacterial activity of TLR agonist (TLR2/TLR1 and/or TLR2/TLR6) activated adipose-derived canine MSCs (AD-MSCs) on multi)drug resistant isolates including Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa regarding bacterial growth, and minimum inhibitory concentration (MIC) determination. Effects on bacterial morphology were assessed by electron microscopy. Our results showed that the AD-MSCs conditioned medium primed with different TLR agonists inhibited the growth of E. coli and S. aureus, but it had a decreased effect on E. faecalis and P. aeruginosa. Despite this, AD-MSCs conditioned medium prepared with the combination of TLR agonists exhibited antibacterial activity against all isolates. These findings were in parallel with MIC levels of conditioned media. We conclude that adipose-derived canine MSCs primed with TLR agonists (TLR2/TLR1 and TLR2/TLR6 combination) possess antimicrobial activity against multi-drug resistant isolates of E. coli, S. aureus, E. faecalis and P. aeruginosa. Further studies for testing in in vivo models are being planned to assess the potential application of AD-MSCs as an adjunct treatment modality for multi drug resistant infections. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a global health problem. In particular, chickens are the source of antibiotic resistance and resistance genes. In this study, it was aimed to investigate the Gram-negative bacterial species that cannot ferment lactose from cloacal swap samples and to determine the antibiotic resistance profiles. Identification of the bacteria was performed with MALDI-TOF-MS and multidrug resistance was determined by disk diffusion test. In addition, the presence of ESBL, AmpC and carbapenemase in isolates was investigated by CLSI directions. Totally, 27 isolates were collected and 20 of them were Escherichia coli, 4 of them were E. fergusonii and 1 isolate of Pseudomonas fulva, Aeromonas media, Serratia marcescens. 19 different antibiotic discs from 7 different classes were used in the study and 63% of bacteria had resistance to antibiotics from 3 or more classes. While the highest resistance rate was observed in tetracycline (74.07%), all isolates were found that sensitive to imipenem. While carbapenemase could not be detected in any isolate, it was observed that P. fulva had ESBL and AmpC. Also, PCR was conducted for blaCTX-M, CIT, blaKPC genes in P. fulva. It was found that the bacterium had only blaCTX-M gene. As a result, although it is pleasing to find low presence of beta lactamase, high multidrug resistance has been determined in bacteria. This situation suggests newer therapeutic approaches. In addition, considering the "One Health" concept, antibiotic resistance should be constantly monitored with the interaction of the animal-human-environment. Because the development of resistance is in a constant state of change between bacteria. [ABSTRACT FROM AUTHOR]

Copyright of Mersin Üniversitesi sağlık Bilimleri Dergisi is the property of Mersin University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: The search for treatment success in gallbladder carcinomas, which is one of the tumors with the most aggressive course, poor prognosis, and tendency to show resistance to treatment, continues today. Treatments targeting pathways related to genetic changes detected in most solid tumors offer new hope in the treatment of these tumors. Some of these treatment modalities target apoptosis-related pathways, and mammalian target of rapamycin (mTOR), p38, Bcl-2, and caspase-3 are important components of this pathway. Methods: In the study, mTOR, caspase-3, p38, Bcl-2, LL-37, MDR1, multidrug resistance protein (MRP)1, MRP6, and MRP7 immunohistochemical staining were applied to paraffin blocks of 27 gallbladder cancer and 62 cases with gallbladder dysplasia. The immunohistochemically stained sections were evaluated and scored. Results: mTOR, p38, and caspase-3 expressions were found to be significantly increased in dysplasia and tumor groups, and in dysplastic and malignant cells. While there was no significant difference in the expression of MRP1 and MRP7, MRP6 was significantly overexpressed. Conclusion: In this study, increased expression of mTOR, p38, and caspase-3 in the dysplastic and malignant cells of the gallbladder may show that it has a role in the carcinogenesis process in the gallbladder. The study also shows that MRP6 may also play a role in the development of drug resistance in gallbladder carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Incidence of ventilator-associated pneumonia, caused by gram-negative multidrug resistant bacteria, is on the increase and early mortality rate is high. We aimed to investigate the effects of aging, comorbidities, high Charlson comobidity index score, high Acute Physiology and Chronic Health Evaluation II score, leukocytosis, high C-reactive protein level, inappropriate empirical antibiotic therapy and antibiotic resistance on mortality in ventilator-associated pneumonia caused by gram-negative multidrug-resistant bacteria. Methods: The study was planned as a retrospective cohort study. Patients aged 18 years and older who were hospitalized between January 01, 2015, and January 01, 2020, diagnosed with ventilator-associated pneumonia, and had Gram-negative multidrug resistant pathogen was detected in blood and/or bronchoalveolar lavage fluid specimen or quantitative endotracheal aspirate cultures were included in the study. Results: A total of 370 patients were included in the study. Median age of the patients was 74 (19-95) years. Most frequent bacteria was Acinetobacter baumannii (52.4%). Resistance to ceftriaxone, meropenem, and colistin was 99%, 68%, and 4%, respectively. 7-day and 21-day mortality rates were 38.3% (n=142) and 85.1% (n=315). In multivariate analysis, 7-day mortality was associated with a Charlson comorbidity index score of =4, and risk factors for 7-day mortality were septic shock, amikacin resistance, and white blood cell count =15000/mm3. Advanced age was found to be a risk factor for 21-day mortality, and a high Acute Physiology and Chronic Health Evaluation II score and a high Charlson comorbidity index score were associated with 21-day mortality. It was found that the risk of 7-day mortality in patients with tracheostomy was lower than in patients without tracheostomy. Conclusion:Consideration of clinical scoring systems, closer monitoring of elderly patients, following-up with tracheostomy, may provide a decrease in mortality of ventilator-associated pneumonia, caused by multidrug resistant pathogens. [ABSTRACT FROM AUTHOR]

Objective: Sepsis due to the drug resistant infections is associated with the higher mortality rates in an intensive care unit (ICU). The aim of this study was to determine the demographic characteristics of the deceased critically ill patients, prevalence of the sepsis, and extensively drug resistant infectious-related (XDR) deaths within a year in the ICU. Materials and Methods: The data of patients who died in the ICU between January 1, 2019 and 2020 was retrospectively analyzed. Results: Out of 525 patients admitted to the ICU, 269 of them died. One hundred fifty-one of those deceased patients (56.1%) were in medical and 118 (43.9%) in the surgical ICU. Their mean age was 70.5±15 years and 126 (46.8%) of them were female. The mean Acute Physiology and Chronic Health Evaluation-II, Glasgow coma score, Sequential Organ Failure Assessment scores at ICU admission were 23.4±20.9, 9.8±4.4, and 8.2±3.6, respectively. A few reasons for the ICU admission were: respiratory failure (34.9%), neurologic dysfunction (19%), sepsis (17.8%), and cardiovascular failure (16%). Infection occurred in the 231 (85.9%) patients. Of the 109 (40.5%) deceased patients with the diagnosis of sepsis, 48 (40%) of them were admitted in the ICU with sepsis. The most common site of infection was the respiratory system (34.6%). Septic shock was seen in 170 patients (63.2%) and renal replacement therapy was needed in 61 (22.7%) of them. XDR developed in 34.6% of the deceased patients and was more frequent among those with an antibiotic usage before the ICU admission (p=0.02). The mean length of stay at hospital before the ICU admission and length of the ICU stay were 22±25.8 and 10.1±12.7 days, respectively. The number of the deceased medical patients were significantly higher than the surgical patients (p=0.018). Conclusion: The deceased critically ill medical patients were higher than the surgical patients. A total of 40% of the deceased critically ill patients were diagnosed with a sepsis, and one third of them had XDR infection. XDR infections were more frequent among the patients with an antibiotic usage before the ICU admission. [ABSTRACT FROM AUTHOR]

Inappropriate application of antimicrobial agents can result in resistance by bacteria to drugs and changes in bacterial ecology. In particular, the emergence of multi-drug resistant bacteria seriously aff ects the antibacterial efficacy of drugs, which threatens the health and lives of humans and animals. Pharmacokinetic/Pharmacodynamic (PK/PD) models can be used to analyze the relationship between PK and PD data and the antibacterial effect. PK/PD models provide valuable guidance for optimization of dosage regimens, development of new drugs, setting of susceptibility breakpoints, and analyses of resistant mutants. Th e main models of PK/PD integration are in vitro PK/PD, ex vivo PK/PD, and in vivo PK/PD. Each of these models has its own advantages and disadvantages. Hence, knowing how to choose the appropriate PK/PD model has a huge infl uence on obtaining accurate PK/PD data. In this review, we describe the commonly used PK/PD methods. In this way, we provide a reference for optimizing drug regimens and preventing and controlling drug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance among the Enterobacteriaceae members has progressed from multi to extensively drug-resistant status, thereby limiting the treatment options for immunocompromised patients (ICPs). Monotherapy application has been proven unsuccessful in many cases, thereby necessitating a combination therapy for optimal treatment. Materials and Methods: The incidence of extensively drug-resistant (XDR) pathogens among ICPs was studied and they were screened for β-lactamase production, and the effectiveness of antibiotic combination against the XDR Enterobacteriaceae isolated from a Federal Medical Center in Nigeria was determined using the standard Clinical and Laboratory Standards Institute methods. Checkerboard assay was used to determine the synergy between piperacillin-tazobactam (TZP)/amoxicillin-clavulanic acid (AMC) and each of ceftazidime (CAZ), ceftriaxone (CRO), and gentamicin (GN) by using fractional inhibitory concentration indices. Results: A total of 68 Enterobacteriaceae members were isolates and 15 (22.1%) were XDR. Of the 68 isolates, 53.3%, 13.3%, and 0% were extended-spectrum β-lactamases (ESBL), AmpC, and carbapenemase producers, respectively. A resistance to meropenem was expressed by 37.5% in XDR E. coli, 60% in K. pneumoniae, and 100% in Enterobacter aerogene. Equally alarming was the colistin resistance expressed by 50% in XDR E. coli and 20% in K. pneumoniae. Mono antibiotics with favorable activities against the XDR Enterobacteriaceae included colistin, tigecycline, and meropenem. The synergy was observed for XDR E. coli and K. pneumoniae when TZP was combined with CAZ and CRO. No synergy was observed when AMC was combined with either CAZ or GN. Conclusion: This study demonstrated the incidence of XDR Enterobacteriaceae among ICPs and suggested TZP plus CAZ or CRO as a useful treatment combination for infections due to XDR Enterobacteriaceae, including the co-producers of ESBL and AmpC β-lactamase. [ABSTRACT FROM AUTHOR]

Copyright of ANKEM Antibiyotik & Kemoterapi Dergisi is the property of ANKEM Antibiyotik & Kemoterapi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Giriş: Çoklu ilaç dirençli Gram-negatif bakterilerin yol açtığı enfeksiyonlar tüm dünyada ciddi bir halk sağlığı problemidir. Karbapenem dirençli Klebsiella pneumoniae (K. pneumoniae) suşları bu grupta yer alan önemli patojenlerden biridir. Antimikrobiyal direnç oranlarının giderek artması bu izolatlarla gelişen enfekiyonların tedavisinde kullanılabilecek seçenekleri azaltmaktadır. Seftazidim-avibaktam, çoklu ilaç dirençli enfeksiyon etkenleri için tedavi alternatifi olarak görülen bir sefalosporin-beta-laktamaz inhibitörü kombinasyonudur. Bu çalışmada 2018-2023 arası yıllara ait karbapenem dirençli K. pneumoniae izolatlarının seftazidim-avibaktam duyarlılığın ilerleyen yıllar içinde in vitro değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Bu çalışmada 1 Ocak 2018 ile 31 Aralık 2023 tarihleri arasında hastanemizde yatan hastaların çeşitli klinik örneklerinden izole edilen karbapenem dirençli K. pneumoniae suşlarında seftazidimavibaktam duyarlılığı retrospektif olarak araştırıldı. Her hasta için aynı enfeksiyon döneminde alınan tekrarlayan üremeler çalışma dışı bırakıldı. Çalışmaya dahil edilen 122 K. pneumoniae izolatının antibiyotik duyarlılık testleri Kirby-Bauer disk difüzyon yöntemiyle Mueller-Hinton agarda test edildi. Sonuçlar EUCAST (The European Committee on Antimicrobial Susceptibility Testing) standartlarına göre değerlendirildi. Çalışmada kalite kontrol suşu olarak K. pneumoniae ATCC700603 suşu kullanıldı. İstatistiksel analizde IBM SPSS (Versiyon 21, Chicago, IL) programı kullanıldı. Bulgular: Çalışmaya dahil edilen karbapenem dirençli toplam 122 K. pneumoniae izolatı hastanemiz mikrobiyoloji laboratuvarına gönderilen kan, kateter, endotrakeal aspirat, bronkoalveolar lavaj, balgam, idrar, yara, apse, doku, safra, plevra ve assit sıvısı materyallerinden izole edildi. Bu izolatların 118'i (%96,7) seftazidim-avibaktama duyarlı bulundu. Duyarlılık oranları 2 yıllık periyotlar halinde incelendiğinde 2018-2019 yıllarına ait izolatların (n=34) tümü seftazidim-avibaktama duyarlı görülürken, 2020-2021 yıllarına ait izotlarda (n=45) %95,5, 2022-2023 yıllarına ait olanlarda (n=43) ise %95,3 oranında duyarlılık saptandı (p=0,449). Sonuç: Enterobacteriaceae türlerinde gün geçtikçe artan antibiyotik direnci özellikle sağlık hizmeti ilişkili enfeksiyonların tedavisini güçleştirmiş ve yeni tedavi arayışlarını beraberinde getirmiştir. Ülkemizde yine disk difüzyon yöntemiyle yapılmış benzer iki çalışmada karbapenem dirençli K. pneumoniae izolatlarında seftazidim-avibaktam duyarlılık oranları %77,5 ve %77,8 olarak bildirilmiştir. INFORM küresel sürveyans çalışmasında ise meropenem dirençli Enterobacteriaceae izolatlarının %73'ü seftazidim-avibaktama duyarlı olarak raporlanmıştır. Bu sonuçlar göze alındığında hastanemizde 2018-2023 yılları arasında saptadığımız %96,69 oranındaki duyarlılık son derece yüz güldürücüdür. Sonuç olarak çoklu ilaç dirençli mikroorganizmaların yol açtığı enfeksiyonların tedavisinde doğru tedavi stratejilerinin oluşturulabilmesi için her hastanenin kendi direnç profilini belirlemesi gerekmektedir. [ABSTRACT FROM AUTHOR]

The increase in methicillin and multidrug resistance (MDR) of Staphylococcus species, which are frequently isolated from cats and dogs, formed the basis of our study. For this purpose, a total of 142 clinical samples (wound, ear, eye, nasal, skin swabs, etc.) belonging to 100 dogs and 42 cats brought to the Near East University Animal Hospital were studied in our investigation. Species-level identification of Staphylococcus spp. isolated from the samples examined was performed with the VITEK-2 microbial ID/AST test system and API Staph identification system. Antimicrobial susceptibility analyzes of Staphylococcus isolates were carried out through the VITEK-2 automated system. From the samples, 78 (54.92%) Staphylococcus spp. were isolated. 52 (66.67%) of the isolates were identified as Coagulase positive Staphylococcus (CoPS) and 16 (20.51%) as Coagulase negative Staphylococcus (CoNS). Among CoPS, the most frequently identified species were S. pseudintermedius (38.46%) and S. aureus (25.64%); whereas among CoNS, S. chromogenes (10.26%) was determined as the most predominant. According to the results of antimicrobial susceptibility analyzes, 11 (28.2%) isolates were determined as methicillin resistant S. aureus (MRSA), 10 (25.64%) as methicillin resistant S. pseudintermedius (MRSP) and 10 (25.64%) isolate methicillin resistant Coagulase negative Staphylococcus (MRCoNS). Besides, 6 (40.00%) MDR-MRSP and 4 (26.66%) MDRMRSA positivity were determined among the species with multiple drug resistance. Of the 23 MDR Staphylococcus spp. isolates in total, 21 were isolated from dogs and 2 from cats. By analyzing the current approaches of the increased drug resistance with the data obtained in this study in Staphylococcus species isolated from animals, necessary contributions have been implemented to the treatment protocols within this framework. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ankara University Faculty of Medicine / Ankara Üniversitesi Tip Fakültesi Mecmuasi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Complicated by nosocomial infections and wide spectrum antibiotherapy, combat related injuries (CRI) are associated with resistant gram-negative microorganisms, especially at the later stage. The aim of this study is to retrospectively investigate demographic, clinical and microbiologic characteristics of 45 CRI patients transferred from Libya and hospitalized in a private clinic. Material and Method: Surveillance cultures (nasal, rectal, wound swabs, trakeal aspirates, urine and blood cultures) were obtained and isolated bacteria and their antibiotic susceptibility were identified using VITEKR 2 system (bioMerieux, Marcy l'Etoile, France). Results: The median age of 45 patients (44 [97.8%] male) was 30.7}12.9 years. The majority of the injuries were due to firearms (66.7%) and 22 (48.9%) patients were injured on the lower extremities. Open bone fractures were present in 30 (66.6%) patients. Primary wound site infection was present in 28 (62.2%) patients. Surveillance cultures revealed 40 microorganisms from the samples of 29 patients, which were gram-negative rods in 22 (55%), gram-positive cocci in 17 (42.5%) and fungus in 1 (2.5%) patients). Of the 40 isolated microorganisms, 13 (32.5%) were non-resistant, 10 (22.2%) were MDR, and 13 (28.9%) were XDR. None of the patients died in the study period. Conclusion: Despite the limited number of cases, this study presents the characteristics of the Libyan combat victims treated by a multidisciplinary team at a single center. Surveillance cultures revealed many victims to be infected or colonised by MDR/ XDR bacteria. Early surgical wound debridement, early initiation of antibiotic therapy in the proper dose and spectrum, and obtaining wound site cultures whenever necessary may help to provide more favorable outcomes in CRI victims. [ABSTRACT FROM AUTHOR]

Objectives: Mycobacterium tuberculosis is the causative organism of tuberculosis, which is the most lethal disease after cancer in the current decade. The development of multidrug and broadly drug-resistant strains is making the problem of tuberculosis more and more critical. In the last 40 years, only one molecule has been added to the treatment regimen. Generally, drug design and development programs target proteins whose function is known to be essential to the bacterial cell. M. tuberculosis possesses specialized protein export systems like the SecA2 export pathway and ESX pathways. Materials and Methods: In the present communication, rational development of an antimycobacterial agent's targeting protein export system was carried out by integrating pocket modeling and virtual analysis. Results: The 23 identified potential lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like infrared and nuclear magnetic resonance spectroscopy, and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds showed profound antimycobacterial activity. Conclusion: We found that Q30, M9, M26, U8, and R26 molecules had significant desirable biological activity and specific interactions with Sec of mycobacteria. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidates with fewer side effects. [ABSTRACT FROM AUTHOR]

Infection is a major cause of morbidity and mortality in burns patients. In spite of considerable advances in the treatment of burns, infection continues to pose the greatest danger to burn patients. We aimed to evaluate and present risk factors for multidrug resistant (MDR) Pseudomonas aeruginosa and Acinetobacter baumannii infections which are considered as a challenge to burns. From January 2009 to May 2011, a total of 465 patients hospitalized in Burn Care Unit were retrospectively reviewed including bacteria isolated and antibiotic susceptibility tests. The mean age of patients was 18.6 ±22.0 yr (median=6,1-87 yr). Use of invasive device, lenght of stay in hospital, Intensive care unit lenght of stay and percentage of Total Body Surface Area were statistically significant for MDR A. baumannii and P. aeruginosa. In logistic regression, length of stay and the invasive device usage were found as risk factors for MDR A. baumannii and P. aeruginosa. Strict rules to control infections, lower hospitalization period and reducing the invasive device usage are essential to keep MDR and Nosocomial infections (NIs) rates lowered or at least in a stable phase. [ABSTRACT FROM AUTHOR]

In this study, the investigation of the antibiotic resistance gene profiles of Staphylococcus aureus isolates from foods of animal origin was aimed. Totally, 95 S. aureus strains, obtained during a period between 2009 and 2012, from culture collection of the Food Hygiene and Technology Laboratory, were examined. The isolates were confirmed by phenotypic tests and PCR. The antibiotic susceptibilities of the isolates were analyzed by disc diffusion method and the minimal inhibition concentrations of the antibiotics were determined by E test. PCR were also utilized for determining the presence of resistance genes including blaZ, ermA, ermC, tetK, tetM, mecA, VanA, VanB, VatA, VatB and aacA-aphD. Resistance to penicillin, tetracycline, vancomycin, erythromycin, cefoxitin, gentamycin and quinupristin-dalfopristin were evident as 81.1%, 28.4%, 18.9%, 17.9%, 9.4%, 9.4% and 3.2% respectively. E test results were compatible with the disc diffusion method. Multidrug resistance was observed from 29.5% of S. aureus isolates. Positive compatibility was observed between conventional methods and PCR for the resistance of the isolates, except for vancomycin. In addition, all of the tested isolates found to include a resistance gene for at least one antibiotic. In conclusion, more efficient interventions must be followed to control the redundant use of antibiotics in veterinary practice. Furthermore, appropriate control measures are needed to be implemented to reduce contamination and the spread of multiresistant S. aureus strains. [ABSTRACT FROM AUTHOR]

Herein, oxipropanolamine derivatives from α-naphthol compound were synthesized and the activities against MDR (multi-drug resistant) bacteria were evaluated. Strains of S. aureus which is one of Gram-positive bacteria and A. baumannii, P. aeruginosa, E. coli which are of Gram-negative bacteria were used.The tested bacteria are Grampozitif stain of S. aureus and Gram-negatif stains of A. baumannii, P. aeruginosa, E. coli. For the synthesis of compounds 2a-d which were used in the study, firstly 2-((naphthalen-1-yloxy)methyl) oxirane was obtained with the reaction of α-naphthol with epichlorohydrin and then reacted with four diffrent amine groups to obtain 2a-d derivatives. While the obtained compounds 2a, 2b and 2c have more antibacterial activity than other tested antibacterials, the compound 2d has shown moderate or blow antibacterial activity against Gram-negative bacteria, but has a high activity against gram-positive bacteria S. aureus. [ABSTRACT FROM AUTHOR]

Merkezi sinir sisteminin gerek yapı ve fonksiyonunu gerekse patolojisini hücresel düzeyde anlamada nöronal ve glial paradigma olmak üzere iki yaklaşım öne çıkmaktadır. Nöronal paradigma nöronları, glial paradigma ise glia hücrelerini vurgulayarak patolojiyi açıklamakta ve anlamlandırmaktadır. Beyin tümörlerinin en yaygın türlerinden biri olan glioblastoma, konumu, sağ kalım süresinin kısalığı ve ilacın hedef dokuya ulaşabilirliğinin zorluğu noktalarından özgün bir tümördür. Glioblastomalarda kemoterapötik tedavi- de gözlenen ilaç direnci, diğer tümörlerde gözlenen direnç mekanizmalarıyla uyumludur. Bu direnç mekanizmaları, tümör hücreleri- nin ilaca hassasiyetini azaltan kan beyin bariyeri ve membran transport proteinlerine bağlı olarak hücre içine ilaç girişinin azalması, DNA tamir sistemlerindeki adaptif cevap ve hedef molekülün ilaca bağlanma etkinliğinin azaltılması ve ilaçların hedef dokudaki et- kin konsantrasyonunu azaltan mekanizmalar detoksifikasyonda rol alan proteinlerdeki değişimler, tümör mikroçevresinde meydana gelen hipoksik bölgeler olmak üzere iki alt başlıkta incelenebilir. Ayrıca, onkogenlerin aktivasyonu ve apoptozisle ilişkili Bcl-2 ailesi proteinlerinin ifadesindeki düzensizliklerin de ilaç direncinin ortaya çıkışında rol aldığı bilinmektedir. Bu derlemede glioblastoma tümörlerinde görülen çoklu ilaç direncinin olası mekanizmalarını güncel literatür ışığında tanımlanarak sistemik ve bütüncül bir bakış açısı ortaya konulmaya çalışılmıştır

Purpose: This study aims to determine the risk factors associated with multi-drug-resistant Pseudomonas aeruginosa (MDR-Pa) infections. Methods: A case control study was conducted at the Dicle University Hospital which is 1150-bed tertiary care teaching hospital in Diyarbakir, Turkey. The study cases were recruited from patients with nosocomial MDR-Pa infections. Two control cases were arranged to compare risk factors of MDR-Pa infections. One of the control groups was composed of patients with non-MDR-Pa infections and the other group with non-MDR Gram-negative bacterial infections except P. aeruginosa. Results: Overall, 225 patients were included in the study, 75 with MDR-Pa infections, 150 control cases (75 non-MDR-Pa and 75 MDR Gram-negative non P. aeruginosa infections). The incidence of MDR-Pa infections was found as 3.1/1,000 admissions. Multivariate analysis showed that multiple invasive procedures (Relative Risk 24.57 (95% Confidence Interval 4.45-135.73) p<0.001), burn (RR 13.66 (CI 407-45.80) p<0.001), malignity (RR 12.50 (CI 2.64-59.20) p=0.001), pneumonia (RR 11.91 (CI 2.44-58.16) p=0.002), carbapenem use (RR 4.92 (CI 1.60-15.09) p=0.005) and long hospitalization (> 10 days) (RR 4.68 (CI=2.09-10.49) p<0.001), were found to be risk factors for MDR-Pa. Conclusions: This study revealed that severity of clinical course and carbapenem use are significant risk factors for MDR-Pa infections. [ABSTRACT FROM AUTHOR]

Giriş: Son yıllarda karbapenem direncinin yayılması küresel bir sağlık sorunudur. Karbapeneme dirençli Acinetobacter baumannii, Pseudomonas aeruginosa, 3. kuşak sefalosporinler ve karbapenemlere dirençli Enterobactericea (Escherichia coli, Klebsiella pneumoniae) kritik öneme sahip Gram-olumsuz bakterilerdir. Özellikle yoğun bakım ünitelerinde yatan hastalarda bu etkenlerle gelişen enfeksiyonların tedavisi zor ve mortalitesi yüksektir. Yeni tedavi seçeneği olarak seftazidim-avibaktam (CAZ-AVI) yapılan çalışmalarda çoklu antibiyotik direnci gösteren Gram-olumsuz enterik basillere ve pseudomanas türlerine etkili saptanmıştır. Bu nedenle hastanemizde CAZ-AVI ile tedavi ettiğimiz hastaların verilerini analiz ederek tedavi deneyimimizi paylaşmayı amaçladık. Gereç ve Yöntem: CAZ-AVI tedavisi verilen 36 hastanın %75’i erkek ve ortanca yaş 63 (20-91) olarak saptandı. Enfeksiyonların %40,8’i pnömoni, %38,8’i kan dolaşım enfeksiyonu, %10,2 deri-yumuşak doku enfeksiyonuydu. On iki hastada birden fazla enfeksiyon tablosu mevcuttu. Pnömoni gelişen hastalardan alınan endotrakeal aspirat kültürlerinde en sık izole edilen etkenler sırasıyla Klebsiella spp. (%57,1) ve Pseudomonas aeruginosa (%17,8) oldu. Tüm izolatlardaki kolistin direnci %42,8 idi. Bakteriyemi gelişen 19 hastadan toplamda 21 etken izole edildi. Bakteriyemide en sık saptanan etken ise %80,9 ile Klebsiella spp. oldu ve tüm izolatlardaki kolistin direnci %66,6 idi. Bulgular: Hastaların tedavi süresi ortanca 14 (3-14) gündü. Yedi (%19,4) hastada CAZ-AVI monoterapi olarak tedavide kullanıldı. Kombinasyonlar %47,2 ikili, %30,6 üçlü ve %2,8 dörtlüydü. Kombinasyonda en sık kullanılan antibiyotikler ise teikoplanin (%22,4), kolistin (%16,3), tigesiklin (%12,2) ve amikasindi (%10,2). Hastaların 28 günlük mortalite oranı %36,1 olarak saptandı. Sonuç: CAZ-AVI, ülkemizde Ekim 2019’da ruhsat almış olmasına rağmen geri ödeme koşulları ancak 28 Nisan 2021 tarihinde sağlanabilmiştir. İkinci ve/veya üçüncü basamak yoğun bakım ünitelerinde yatan hastalarda; komplike intraabdominal enfeksiyon, piyelonefrit dahil komplike idrar yolu enfeksiyonu veya ventilatör ile ilişkili pnömoni dahil hastanede kazanılmış pnömoni tedavisinde endikasyon almıştır. CAZ-AVI özellikle çoklu ilacadirençli Gram-olumsuz bakterilerde etkili bir alternatif olarak karşımıza çıkmakta; ancak halen daha fazla hasta izleminin yapıldığı prospektif gözlemsel çalışmalara ihtiyaç duyulmaktadır. [ABSTRACT FROM AUTHOR]

Objective: Corynebacterium striatum strains are members of the normal flora of skin and mucous membranes, and commonly found in the environment. They have been regarded as contaminant for a long time when they reproduce in microbiological cultures. Lately, increase in the number of immunosuppressive patients and invasive procedures, and more frequent use of wide-spectrum antibiotics caused an increase in the number of reported infections and epidemics related to C. striatum strains. In this study, C. striatum isolates which are regarded as the infectious agents according to the microbiological criteria and their susceptibility to antibiotics were evaluated in our hospital for the last five years period and it was tried to attract the attention to this opportunistic pathogen having rapidly increasing isolation frequency. Methods: Various clinical samples sent to our hospital’s Medical Microbiology Laboratory were Gram stained, and cultured in appropriate agars. The strains with leucocytes and/or bacteria on Gram stain, dominant or absolute growth in culture, and growth in the repeated cultures were regarded as infectious agents while bacterial growths not fulfilling those criteria were reported as contamination or colonization. Identification of the agents at stain level was performed with Vitek 2 (bioMerieux, France) system between 2010 and 2013, and with Bruker Microflex MS (Bruker Daltonics, Bremen, Germany) system in 2014. Results: The numbers of C. striatum strains that were regarded and reported as infectious agents according to microbiological criteria between 2010 and 2014 were 52, 73, 191, 199, and 231, respectively (total 746). Among those, 369 (49.5%) strains were isolated from wounds, 149 (20.0%) from tracheal aspirates, 140 (18.8%) from blood, 38 (5.1%) from sterile body fluids, 31 (4.2%) from urine, and 19 (2.5%) from abscesses. The agents were most frequently isolated from ICU patients (37.9%). According to the antibiotic susceptibility test results it was observed that all agents were multiresistant. In the evaluation performed according to CLSI guidelines between the years 2010 and 2013 the ciprofloxacin, penicillin, rifampicin, clindamycin, tetracycline, and gentamycin resistance were found as 83.0%, 80.0%, 79.1%, 73.2%, 69.9%, 41.2%, 17.6% respectively and also it was observed that all the strains were susceptible to vancomycin and linezolid. In the evaluation performed according to EUCAST guideline in 2014 it was observed that all strains were susceptible only to vancomycin and linezolid, and resistant to all other antimicrobials. Conclusion: C. striatum isolates are becoming more and more frequently seen pathogens in the clinical microbiology laboratory. Missing their diagnosis as pathogens particularly in immunosuppressive patients and/ or in the ones on long-term treatment with widespectrum antibiotics may result in mortality. In this study, we tried to draw attention to this opportunistic, multiresistant pathogen with an increasing isolation rate in our hospital. Corynebacterium strains that may act as infectious agents according to microbiological criteria particularly in risky patient groups must be identified at strain level, their antimicrobial susceptibility tests must be performed, and the patients must be treated accordingly. [ABSTRACT FROM AUTHOR]

Objective: In the present report we were interested in to determine the community associated Urinary Tract Infections (UTI) causing uropathogen's prevalence, the antibiotic resistance patterns and the risk factors associated with it in the Parhon Hospital Iasi, the most important clinical facility of this type from Moldova region in Romania. Material and Method: This was a retrospective chart review-study We considered as multi-drug resistant, those germs that were resistant to more than five antibiotics. In addition, we were interested in better understanding the other variables associated with the positive urine culture and their value as main risk factors in UTI, as studied from the patients charts. Results: Our data showed that mainly the most problematic germs were represented by Klebsiella pneumoniae/spp, Pseudomonas aeruginosa, Escherichia coli and Staphylococci (coagulase-negative/S. aureus/S. saprophiticus). Also, the bacteria responsible for UTI multidrug resistant (MDR) development presented a 100% resistance to the following 9 antibiotics: amoxicillin, ticarcillin, cefalexin, cefaclor, ceftibuten, penicillin, oxacillin, erythromycin and ceftaroline. In addition, for the first time in our country, a specific profile for the UTI MDR-risk patient was described in the present paper. Conclusion: Thus, treatment for UTI should be done in accordance with the antibiogram results and for a sufficient period of time, in order to avoid the appearance of pan-resistant germs for which there are no reserve antibiotics available. Also, discarding certain commonly used antibiotics, to which the great majority of the strains are resistant, for a period of time, could perhaps lead to a possible shift in the spectrum of their sensitivity. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to determine the types of specimens, distribution among clinics and antibiotic susceptibilities of 531 Acinetobacter baumannii strains isolated in our laboratory between January 2012-June 2014. Methods: Acinetobacter baumannii isolates were identified by conventional methods and API 20 NE (bioMerieux, France), antibiotic susceptibility tests were performed according to the Clinical and Laboratory Standards Institute guidelines except tigecycline evaluated according to Food and Drug Administration guidelines. Results: Strains were isolated from Anesthesiology and Reanimation Unit (36.9%), Medical Intensive Care Unit (17.9%), Neurological Intensive Care Unit (14.7%), Surgical Intensive Care Unit (13.9%), Coronary Intensive Care Unit (2.3%), Internal Medicine Services (9.8%) and Surgical Services (4.5%). Specimen types were; 239 (45.0%) tracheal aspirate, 92 (17.3%) urine, 78 (14.7%) blood, 55 (10.4%) wounds, 38 (7.1%) sputum and 29 (5.5%) catheter. The antibiotic resistance rates were found as 99.1% for nitrofurantoin, 98.9% for cefotaxime, 97.7% for tetracycline, 97.4% for piperacillin, 97.2% for netilmicin, 94.9% for ceftazidime, 94.7% for cefepime, 92.8% for piperacillin/tazobactam, 91.7% for ampicillin/sulbactam and ciprofloxacin, 91.1% for meropenem, 89.8% for imipenem, 89.5% for levofloxacin, 82.1% for gentamicin, 81.2% for trimethoprim/sulfamethoxazole, 79.3% for amikacin, 69.5% for cefoperazone-sulbactam, 25.4% for tobramycin, 5.1% for tigecycline and 0.8% for Colistin. Conclusion: Our strains were found as sensitive to Colistin, tigecycline, tobramycin and cefoperazone/sulbactam antibiotics. Resistance to carbapenems and other antibiotics were remarkable. [ABSTRACT FROM AUTHOR]

This research was conducted to investigate the extended spectrum beta-lactamase activity and multidrug resistance of Salmonella serovars isolated from chicken carcasses. For this purpose, 99 Salmonella isolates from 930 chicken carcasses were tested against 12 different antimicrobials. The resistance rates of Salmonella isolates to antimicrobials were as follows: 35.3% (35/99) to ampicillin, 33.3% (33/99) to tetracycline, 29.2% to amoxicillin-clavulanic acid, 18.1% (18/99) to nalidixic acid, 17.1% (17/99) to chloramphenicol, 16.1% (16/99) to aztreonam, 12.1% (12/99) to trimethoprim-sulfamethoxazole, 4% (4/99) to gentamicin, 1.0% (1/99) to ceftazidime. Of the isolates 46.4% (46/99) were found to be resistant to two or more antimicrobials as a multidrug resistance. Extended spectrum beta-lactamase activity was detected in 1.0% (1/99) of the isolates. Furthermore, S. Typhimurium 26.2% (28/99), S. Infantis 16.1% (16/99), S. Hadar 12.1% (10/99) and S. Branderburg 9.0% (9/99) were found to be the predominant serovars. In conclusion, antimicrobial resistance and also multidrug resistance rates of Salmonella isolates in this study, indicated that monitoring of antimicrobial resistance profiles is important for Salmonella infections to plan treatment strategies. [ABSTRACT FROM AUTHOR]

(A. baumannii) is a non fermantative gram negative coccobacillus that may cause hospital infections with difficulties in treatment high mortality rates due to its ability to have multiple drug resistance. During recent years, resistance to a lot of antimicrobials including carbapenems in A.baumannii strains results in problems in treatment. Antibiotic combinations are suggested in the treatment of infections caused by multi-drug resistant A. baumannii strains. Postoperative mediastinitis is a rare condition with a high mortality rate. The combination of rifampicin and colistin is an appropriate treatment choice in case of mediastinitis caused by multi-drug resistant A. baumannii. In this case report, we describe a patient who experienced mediastinitis due to A. baumannii infection after coronary artery bypass surgery that was successfully treated with rifampicin and colistin combination. [ABSTRACT FROM AUTHOR]

In cellular perspective, neuronal and glial paradigms are two prevailing approaches for understanding both structure/function and pathology of central nervous system. Neuronal paradigm explains brain pathology mainly based on neurons, while glial paradigm put more emphasize to glial cells. Glioblastoma, one of the most common brain tumors, is unique due to its location, the shortness of median survival and the difficulty of efficient uptake in target tissue. Drug resistance mechanisms observed in the chemotherapy of glioblastoma are quite similar to the ones of other tumor types. These mechanisms can be investigated under two main groups: one is decreasing the sensitivity of tumor cells to chemotherapeutic agents (decreasing of drug uptake into cell by blood brain barrier and membrane transport proteins) and the other one is reducing the efficient concentration of the drug in target tissue (variabilities in detoxification proteins and hypoxia in the tumor microenvironment). Moreover, activation of oncogenes and abnormalities of expression of Bcl-2 protein family members are mediating players in the development of drug resistance in glioblastoma. In this review, the possible drug resistance mechanisms in glioblastoma were described in the light of recent literature by using systemic and integrative perspective. [ABSTRACT FROM AUTHOR]

Amaç: Acinetobacter baumannii; yoğun bakım ünitelerinde çoklu organ yetmezliğine neden olabilen gram negatif fırsatçı patojenlerden birisidir. Acinetobacter baumannii tedavide kullanılan antimikrobiyal ajanlara karşı artan oranda direnç geliştirmektedir. Çoklu ilaca dirençli (en az üç farklı antimikrobiyal sınıfına dirençli) Acinetobacter baumannii suşlarına bağlı enfeksiyonlarda son yıllarda artış mevcut olup bu enfeksiyonların tedavisinde sıklıkla kullanılan kolistine karşı da direnç bildirilmiştir. Bu çalışmamızda; yoğun bakım ünitesinde çoklu ilaç dirençli Acinetobacter baumannii enfeksiyonu bulunan hastaların klinik özelliklerini ve sonuçlarını değerlendirmeyi amaçladık. Gereç ve Yöntem: 1 Ocak 2021-1 Ocak 2022 tarihleri arasında Akdeniz Üniversitesi Tıp Fakültesi Hastanesi Yoğun Bakım Üniteleri’mizde takip ettiğimiz çoklu ilaca dirençli Acinetobacter baumannii enfeksiyonu bulunan hastaların verileri retrospektif olarak incelenmiştir. Etik kurul onayı alınmıştır. Bulgular: Çalışmaya alınan sürede yoğun bakım ünitelerimizdeki toplam 1.734 hastanın verileri incelendi ve doğrulanmış laboratuvar kültürü ile çoklu ilaç dirençli Acinetebacter baumannii enfeksiyonu bulunan 103 hasta örnekleme dahil edildi. Hastaların %65’i erkek, %35’i kadındı. Yaş ortalaması 57,8±19,1, Charlson komorbidite indeksi 6 (IQR1-10), APACHE II skoru ortalaması 19,2±7,9 idi. Yoğun bakıma alınma nedenleri arasında akut solunum yetersizliği en yüksek sıklıkta bulundu. Yüz üç hastadan 26’sının COVID pnömonisi, 9’unun ise son 3 ay içinde geçirilmiş COVID enfeksiyonu vardı. Hastaların %79,8’inde trakea, %14,3’ünde kan kültürü Acinetobacter baumannii pozitifliği mevcuttu. On altı (%15) hastada kolistine dirençli, 87 (%85) hastada sadece kolistin duyarlılığı bulunan Acinetobacter baumannii suşu saptandı. Kültür sonucunun tespiti sonrası Acinetobacter baumannii tedavisine yönelik hastaların 32’si (%31) monoterapi (kolistin), 51’i (%49) ikili antibiyoterapi (kolistin, meropenem), 18’i (%17) üçlü antibiyoterapi (kolistin, meropenem, trimetoprim-sulfametoksazol), 2’si (%1) dört ve üstü antibiyoterapi (üçlü antibiyoterapiye ek olarak yüksek doz ampisilin sulbaktam) almaktaydı. Doksan iki (%89) hastada sepsis, 77 (%75) hastada septik şok, 57 (%55) hastada ilk 28 günde mortalite gelişmiş olup genel mortalite %63 olarak bulundu. Sonuç: Çalışmamızın verilerileri çoklu ilaç dirençli Acinetobacter baumannii enfeksiyonunun çoklu antibiyoterapi seçenekleri kullanılmasına rağmen yoğun bakım ünitelerinde yüksek mortaliteyle ilişkili olduğunu göstermiştir. Acinetobacter baumannii enfeksiyonlarında hasta sonuçlarının iyileştirilebilmesi için etkili enfeksiyon kontrolü ve tedavide yeni antimikrobiyal ajanlara ihtiyaç duyulmaktadır. [ABSTRACT FROM AUTHOR]

Objective: Burn wound infections are the most severe cause of mortality in patients in the burn units. The aim of this study is to determine the bacteriological profile and their antibiotic resistance patterns in burn unit of Dicle University Hospital. Methods: Medical records of 151 burn patients admitted to the burn unit of Dicle University Hospital between June, 2008 and June 2010 were reviewed retrospectively. Results: Our study included 70.2% (n=106) male and 29.8% (n=45) female patients. The mean age of cases was 10.9±14.7 years. The rate of isolated microorganisms were 62.3% (n=94) Acinetobacter baumannii, 25.8% (n=39) Pseudomonas aeruginosa, 7.3% (n=11) Escherichia coli and 4.6% (n=7) Staphylococcus aureus. The most effective antibiotic against A. baumannii was colistin (95%) followed by levofloxacin (84%) and trimethoprimsulfamethoxazole (87%). The most effective antibiotics against P. aeruginosa were amikacin (82%), ciprofloxacin (71%) and levofloxacin (71%). The most effective antibiotics against E. coli were amikacin (91%), meropenem (73%) and imipenem (82%). Conclusion: The prevalence of burn wound infection caused by A. baumannii and multiple drug resistant A. baumannii are increasing worldwide by time. The prevalence of multiple drug resistant P. aeruginosa and E. coli are rising also. So, new strategies of infection prevention should improve as soon as possible. [ABSTRACT FROM AUTHOR]

Objective: Multidrug resistance is a cause of treatment failure in patients with malignant lymphoma; however, the frequency and clinical relevance of multidrug resistance protein expression are unclear. The present study aimed to investigate expression of the most common multidrug resistance proteins in a group of lymphoma patients. Material and Methods: The study included 44 previously untreated lymphoma patients (non-Hodgkin's lymphoma [n = 21], non-malignant lymphadenopathy [n = 13], and Hodgkin's lymphoma [n = 10]). MDR1, MRP, and LRP expression was assessed via quantitative PCR of lymph node biopsy specimens. Results: In the non-Hodgkin's lymphoma group MDR1 was positive in 23.8% (5/21) of the patients, MRP was positive in 57.14% (12/21), and LRP was positive in 90.47% (19/21). In the non-malignant lymphadenopathy group, MDR1 was positive in 46.15% (6/13) of the patients, MRP was positive in 84.61% (11/13), and LRP was positive in 100% (13/13). In the Hodgkin's lymphoma group MDR1 was positive in 50% (5/10) of the patients, MRP was positive in 50% (5/10), and LRP was positive in 80% (8/10). MDR1, MRP, and LRP expression did not differ between the 3 groups. Furthermore, MDR1, MRP, and LRP expression wasn't associated with tumor stage, response to first-line therapy, the erythrocyte sedimentation rate, or C reactive protein, beta 2 microglobulin, serum lactate dehydrogenase, and albumin levels. Additionally, survival time in the MDR1- and MRP-positive, and MDR1- and MRP-negative patients did not differ (comparison of LRP was not possible due to the small number of LRP-negative patients). Conclusion: According to the present findings, future studies should investigate alternative pathways of multidrug resistance in order to arrive at a better understanding of treatment failure in lymphoma patients. [ABSTRACT FROM AUTHOR]

Aim: To characterize common beta-lactamase genes and the role of integrons in beta-lactam antibiotic resistance among multidrug-resistant (MDR) P. aeruginosa strains isolated from intensive care units in Turkey. Materials and methods: After the examination of 67 P. aeruginosa isolates, 14 were found to be resistant to all of the tested beta-lactams and aminoglycosides. These 14 strains were studied to characterize the beta-actamases and related integrons. Evaluation of minimum inhibitory concentrations, polymerase chain reaction (PCR) screening, isoelectric focusing, outer membrane isolation and analysis, and cloning and sequencing were performed according to published protocols. Results: PCR screening for common beta-lactamases detected PER-1 and OXA-10 among the selected MDR P. aeruginosa. PCR screening results showed that 2 of the isolates had 5'-3' class I integrons. Sequence analysis of the integrons revealed the existence of 6'-N-acetyltransferase (aac(6)-Ib) and streptomycin 3'-adenyl transferase (aadA2) cassettes (GenBank accession no. EF368053). Coexistence of PER-1 and OXA-2 and of PER-1 and OXA-10 was demonstrated in 8 and 7 of the isolates, respectively, by PCR. Shotgun cloning and PCR screening with relevant primers revealed the existence of a class I integron-associated blaOXA-2 gene cassette in 2 of the isolates. Strains positive for OXA-2 were also positive for PER-1. Conclusion: This study demonstrated the coexistence of PER-1 and OXA-2 in a single host. Coexistence of PER-1 with OXA-2 may increase the risk of the spreading of MDR P. aeruginosa in Turkish hospitals. [ABSTRACT FROM AUTHOR]

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The cells developing resistance to an applied drug may also present cross-resistance to other anticancer drugs which are not applied. In this study, the development of cross-resistance in paclitaxel (MCF-7/Pac), docetaxel (MCF-7/Doc), vincristine (MCF-7/Vinc) and doxorubicin (MCF-7/Dox) resistant MCF-7 cells to selective anticancer drugs, tamoxifen and all trans-retinoic acid (ATRA) were investigated. Combined antiproliferative effects of these drugs in different combinations were also evaluated by checkerboard combination assay. MCF-7/Pac and MCF-7/Doc cells developed cross-resistance to vincristine (13- and 12-folds, respectively) and tamoxifen (3- and 2-folds, respectively). MCF-7/Dox cells developed cross-resistance to paclitaxel (109-fold), docetaxel (10-fold), tamoxifen (2-fold) and ATRA (3-fold). MCF-7/Vinc cells developed cross-resistance to paclitaxel (48-fold), doxorubicin (6-fold) and tamoxifen (2-fold). Combinations of paclitaxel and docetaxel with doxorubicin exerted synergic antiproliferative effect. Tamoxifen had synergic effect with doxorubicin and vincristine. ATRA had indifferent effect with paclitaxel, docetaxel and doxorubicin where it had antagonistic effect with vincristine. The data presented here may provide an insight to assess response of breast tumors to anticancer drug combinations. [ABSTRACT FROM AUTHOR]

Giriş: Günümüzde Gram-olumsuz bakterilerde (GNB) direnç giderek artmaktadır. Çoklu ilaca dirençli (ÇİD) izolatlarla gelişen enfeksiyonlar hastalarda yüksek mortalite ve morbidite ile ilişkilidir. Direnç nedeniyle etkin antibiyotik seçenekleri azalmaktadır. Parenteral fosfomisin ÇİD GNB tedavisinde etkili bir alternatif olarak karşımıza çıkmaktadır. Bu nedenle hastanemizde son bir yılda fosfomisin ile tedavi ettiğimiz hastaların verilerini sunmayı amaçladık. Gereç ve Yöntem: Fosfomisin tedavisi verilen 24 hastanın %70,8’i erkek ve ortanca yaş 54,5 (19-74) olarak saptandı. Hastaların %54,2’si yoğun bakım ünitesinde takip edilmekteydi. Enfeksiyonların %37,5’u pnömoni, %25’i üriner sistem enfeksiyonu, %16,6’sı kan dolaşım enfeksiyonu, %16,6’sı batın içi enfeksiyondu. Beş hastada birden fazla enfeksiyon tablosu mevcuttu. Üç (%12,5) hastaya ampirik olarak tedavi başlanmıştı. Kan dolaşım enfeksiyonu saptanan hastalarda izole edilen bakteriler ve direnç profilleri Tablo 1’de özetlenmiştir. Bakteriyemide en sık saptanan etken %42,8 ile Klebsiella spp. olmuş ve bakteriyemi gelişen dört hastadan yalnızca biri eksitus olmuştur. Bulgular: Endotrakeal aspirat kültürlerinde en sık izole edilen etken Acinetobacter spp. (%45,4) olmuştur. Tüm izolatlar karbapenem dirençli, kolistin duyarlıdır. İdrar kültürlerinde en sık izole edilen etken Klebsiella spp. (%60) olmuştur ve %66,6 karbapenem direnci saptanmıştır. Kolistin direnci saptanmamıştır. Deri-yumuşak doku ve batın içi enfeksiyon saptanan hastalardan alınan yara, doku ve apse kültürlerinde en sık izole edilen etken yine Klebsiella spp. (%42,8) olmuştur ve %33,3 karbapenem direnci, %66,6 kolistin direnci saptanmıştır. Hastaların tedavi süresi ortanca 10 (3-21) gündür. Üriner sistem enfeksiyonu nedeniyle takip edilen üç (%12,5) hastada fosfomisin monoterapi olarak kullanılmıştır. Kombinasyonlar %29,2 ikili, %54,2 üçlü, %4,2 dörtlü olarak kullanılmıştır. Kombinasyonda en sık kullanılan antibiyotikler karbapenemler (%30,8), kolistin (%12,8) ve tigesiklindir (%12,8). Hastaların 28 günlük mortalite oranı %37,5 olarak saptanmıştır. Sonuç: Fosfomisin, özellikle duyarlı olan etkenlerle gelişen enfeksiyonlarda, olumlu bir güvenlik profili sergilemektedir. ÇİD GNB enfeksiyonlarında halen ilgi çekici bir alternatif olmayı sürdürmektedir; ancak hızla direnç gelişebilmesi ve ciddi enfeksiyonu bulunan hastalarda yeterli sayıda randomize kontrollü çalışmaların bulunmaması nedeniyle uygun hasta seçiminde dikkatli olmak gerekmektedir. [ABSTRACT FROM AUTHOR]

A 78 year old male was hospitalized in neurology clinic with a diagnosis of encephalopathy. On 13th day of imipenem treatment for ventilator-associated pneumonia (VAP), a new VAP episode was diagnosed based on physical examination, laboratory and radiological findings. Cefoperazone-sulbactam 2×2 gr/day IV was started empirically. In the 3rd day of treatment Acinetobacter baumannii was identified from endotracheal aspirate culture that was resistant to all other antibiotics including colistin except cefoperazone-sulbactam (intermediate) and tigecycline (MIC: 4 mg/L, intermediate) by VITEK and E-test. Tigecycline 2 × 50 mg (after loading dose of 100 mg) IV, colistin IV 2 × 150 mg and colistin inhaler 2 × 75 mg were added to the cefoperazone-sulbactam 2 × 2 gr IV. Clinical findings were improved under this combination and completed to 14 days. The patient was discharged from hospital with neurological sequel after three months. This case has been presented to emphasize that colistin resistant Acinetobacter baumannii is becoming a problem for our country. [ABSTRACT FROM AUTHOR]