Resistance and heteroresistance to colistin among clinical isolates of Acinetobacter baumannii.

Colistin is one of the most effective alternatives for treating Acinetobacter baumannii infections. The aim of this study was to determine colistin resistance and heteroresistance rates in A. baumannii from clinical samples in Hacettepe University clinical microbiology laboratory between June 2016 and January 2017. A total of 200 isolates were included in the study. In vitro susceptibility to amikacin, gentamicin, ceftazidime, piperacillin/tazobactam, meropenem, ciprofloxacin, and tigecycline were determined by disk diffusion test. Most isolates were multiresistant as they exhibited resistance to aminoglycosides, ß-lactams, and fluoroquinolones. Colistin susceptibility was determined by broth microdilution (BMD) test (EUCAST standards) and was compared with E-test (bioMérieux, France) in 120 isolates. In 14 blood isolates that were susceptible to colistin (MIC ≤ 2 mg/L), heteroresistance was investigated with the population analysis profile (PAP) method. Overall resistance (n = 200) to colistin was 28% by BMD. Among the 120 isolates where the two tests were compared, resistance to colistin was 25.8% versus 4.2% with BMD and E-test, respectively. Three blood isolates (21.4%) were heteroresistant to colistin. With E-test, a majority of the resistant isolates are overlooked and in vitro susceptibility to colistin should be determined with broth dilution method. This is the first study in Turkey reporting heteroresistance in A. baumannii isolates by the PAP method and emphasizes the need to test for heteroresistance in relation to clinical outcome in serious infections due to A. baumannii.

Metastatic meningioma of the scalp.

Meningiomas generally present as slow-growing, expanding intracranial lesions and are the most common benign intracranial tumor in adults. Rarely, meningiomas can exhibit malignant potential and present as extracranial soft-tissue masses through extension or as primary extracranial cutaneous neoplasms. Although they are uncommonly encountered by dermatologists, it is important to include meningioma in the differential diagnosis for scalp neoplasms. We present a rare case of a 68-year-old woman with scalp metastasis of meningioma 11 years after initial resection of the primary tumor.

Trichosporon asahii sepsis in a patient with pediatric malignancy.

Trichosporon asahii is a rare opportunistic infection, especially in children, causing a life-threatening fungal infection underlying hematologic malignancies. Predisposing factors for infection with this pathogen are immunodeficiency including underlying malignancy, organ transplantation, extensive burns, human immunodeficiency virus infection, corticosteroid therapy, prosthetic valve surgery, and peritoneal dialysis. In the literature, a breakthrough under caspofungin, micafungin therapy is reported. In this article we report on a 16-year-old patient with Ewing sarcoma who had T. asahii sepsis. The patient died although he had been receiving caspofungin for less than 3 months and amphotericin B therapy for 3 days. A postmortem study of conchal tissues revealed T. asahii and mucormycosis histopathologically, and blood culture grew T. asahii.

The Prevalence of Vancomycin-Intermediate Staphylococcus aureus and Heterogeneous VISA Among Methicillin-Resistant Strains Isolated from Pediatric Population in a Turkish University Hospital.

There are limited data regarding the prevalence of vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) among pediatric population. Our objective was to determine the distribution of vancomycin and daptomycin minimum inhibitory concentrations (MICs) and explore the phenomenon of vancomycin MIC creep and the VISA/hVISA prevalence among the methicillin-resistant Staphylococcus aureus (MRSA) strains belonging to pediatric population by population analysis profile-area under the curve (PAP-AUC) and Etest macromethod. Vancomycin and daptomycin susceptibilities of 94 pediatric isolates of MRSA were tested by broth microdilution (BMD) and Etest methods. To determine the prevalence of VISA/hVISA, Etest macromethod and PAP-AUC was performed on all isolates. All isolates were susceptible to vancomycin and daptomycin by both BMD and Etest methods. Twenty-eight (29.8%) isolates had vancomycin MICs of 2 µg/ml by BMD. No increase in vancomycin MICs was observed over time. There were no VISA among 94 MRSA tested but 20 (21.3%) hVISA isolates were identified by PAP-AUC. Results of Etest macromethod were compared to PAP-AUC. Etest macromethod was 60.0% sensitive and 90.5% specific. The hVISA isolates represented 53.6% of isolates with vancomycin MICs of 2 µg/ml. Also, 75% of hVISA isolates had vancomycin MICs of 2 µg/ml. To our knowledge, this is the first study investigating the prevalence of VISA/hVISA among MRSA isolated from pediatric patients by PAP-AUC method. Based on our findings, MRSA isolates, which have vancomycin MIC of 2 µg/ml can be investigated for the presence of hVISA. In this study, daptomycin showed potent activity against all isolates and may represent a therapeutic option for MRSA infections.

Vancomycin and daptomycin minimum inhibitory concentration distribution and occurrence of heteroresistance among methicillin-resistant Staphylococcus aureus blood isolates in Turkey.

BACKGROUND: The aim of this study was to determine the distribution of vancomycin and daptomycin MICs among methicillin-resistant Staphylococcus aureus (MRSA) blood isolates, the prevalence of heterogeneous vancomycin-intermediate S. aureus (hVISA) and the relationship between hVISA and vancomycin MIC values. METHODS: A total of 175 MRSA blood isolates were collected from seven university hospitals in Turkey. All isolates were tested for susceptibility to vancomycin and daptomycin by reference broth microdilution (BMD) and by standard Etest method. BMD test was performed according to CLSI guidelines and Etest was performed according to the instructions of the manufacturer. All isolates were screened for the presence of the hVISA by using macro Etest (MET) and population analysis profile-area under the curve (PAP-AUC) methods. RESULTS: The vancomycin MIC50, MIC90 and MIC ranges were 1, 2, and 0.5-2 µg/ml, respectively, by both of BMD and Etest. The daptomycin MIC50, MIC90 and MIC ranges were 0.5, 1 and 0.125 -1 µg/ml by BMD and 0.25, 0.5 and 0.06-1 µg/ml by Etest, respectively. The vancomycin MIC for 40.6% (71/175) of the MRSA isolates tested was >1 µg/ml by BMD. No vancomycin and daptomycin resistance was found among MRSA isolates. Percent agreement of Etest MICs with BMD MICs within ±1 doubling dilution was 100% and 73.1% for vancomycin and daptomycin, respectively. The prevalence of hVISA among MRSA blood isolates was 13.7% (24/175) by PAP-AUC method. MET identified only 14 of the hVISA strains (sensitivity, 58.3%), and there were 12 strains identified as hVISA that were not subsequently confirmed by PAP-AUC (specificity, 92.1%). CONCLUSIONS: Agreement between BMD and Etest MICs is high both for vancomycin and daptomycin. Daptomycin was found to be highly active against MRSA isolates including hVISA. A considerable number of isolates are determined as hVISA among blood isolates. As it is impractical to use the reference method (PAP-AUC) for large numbers of isolates, laboratory methods for rapid and accurate identification of hVISA need to be developed.

Pancreatic mucinous cystic neoplasm with sarcomatous stroma metastasizing to liver: a case report and review of literature.

We report a case of mucinous cystic neoplasm of pancreas with sarcomatous stroma metastasizing to the liver. The tumor occurred in a male patient aged 46 years. Symptoms included persistent epigastric and right upper quadrant pain. Radiographically, the pancreas contained four large cystic masses located in the neck, body, and tail. Histologically, the cysts were lined with benign, mucinous epithelium with underlying bland, storiform, ovarian-like stroma. An undifferentiated focally hyalinized, sarcomatous stroma composed of bland spindle cells showing short fascicular growth pattern and focal nuclear palisading was associated with the epithelial component in one of the cysts. These cells showed strong immunoreactivity with vimentin and inhibin (weak), they were negative for CD34, estrogen receptor, progesterone receptor, androgen, calretinin, S-100, CD117, melan A, chromogranin, and synaptophysin. A morphologically and immunohistochemically identical metastatic sarcomatous focus was identified in the liver without any glandular component. This case is unique in its clinically malignant behaviour and metastatic nature despite its morphologically benign epithelial and stromal components.

Identification of single chain antibodies to breast cancer stem cells using phage display.

Recent evidence suggests that most malignancies are driven by "cancer stem cells" sharing the signature characteristics of adult stem cells: the ability to self renew and to differentiate. Furthermore these cells are thought to be quiescent, infrequently dividing cells with a natural resistance to chemotherapeutic agents. These studies theorize that therapies, which effectively treat the majority of tumor cells but 'miss' the stem cell population, will fail, while therapies directed at stern cells can potentially eradicate tumors. In breast cancer, researchers have isolated 'breast cancer stem cells' capable of recreating the tumor in vivo and in vitro. Generated new tumors contained both additional numbers of cancer stem cells and diverse mixed populations of cells present in the initial tumor, supporting the intriguing self-renewal and differentiation characteristics. In the present study, an antibody phage library has been used to search for phage displayed-single chain antibodies (scFv) with selective affinity to specific targets on breast cancer stem cells. We demonstrate evidence of two clones binding specifically to a cancer stem cell population isolated from the SUMl59 breast cancer cell line. These clones had selective affinity for cancer stem cells and they were able to select cancer stem cells among a large population of non-stem cancer cells in paraffin-embedded sections. The applicability of these clones to paraffin sections and frozen tissue specimens made them good candidates to be used as diagnostic and prognostic markers in breast cancer patient samples taking into consideration the cancer stern cell concept in tumor biology.

Long-term clarithromycin in cystic fibrosis: effects on inflammatory markers in BAL and clinical status.

Macrolides have antiinflammatory effects that are potentially useful in cystic fibrosis (CF). In this placebo-controlled, randomized, double-blind crossover study, 18 CF patients were randomized to receive either clarithromycin (CM) (Group 1) or placebo (Group 2) for three months. After 15 days, the treatments were crossed over. Bronchoalveolar lavage (BAL) was obtained in the beginning and at the end of each treatment period. There was no significant difference in median cell counts and median cytokine levels at baseline, after CM use and after placebo use between the two groups. In Group 2, the median neutrophil elastase (NE) level decreased with CM. Patients had less acute pulmonary exacerbations and median clinical score decreased with CM in both groups. Median z-scores for weight increased with CM in Group 2. We could not demonstrate a fall in proinflammatory cytokines in BAL; however, some improvement in clinical status could be shown with three-month CM.

Stenotrophomonas maltophilia infection of the central venous catheter and lysis of an old thrombosis in a post-bone marrow transplantation child: implications in the fibrinolytic process.

In this report, we describe an 11-y-old girl who developed jugular venous thrombosis after allogeneic bone marrow transplantation for lymphoma and then experienced dissolution of the thrombosis following catheter-related Stenothrophomonas maltophilia bactearemia. The lysis of the old thrombosis around the central venous catheter suggested a local fibrinolytic activity of S. maltophilia. The global fibrinolytic capacity (GFC) was also tested in vitro by using S. maltophilia cultures obtained from the present patient; GFC of the patient was compared to that of another isolate of S. maltophilia, other bacteria (S. pyogenes and E. coli), and control plasma. The fibrinolytic capasity of S. maltophilia was significantly higher than that of the control plasma (p<0.05) and almost equal to that of S. pyogenes (p>0.05). Thus, if a potent local fibrinolytic activity of S. maltophilia is evident, the use of the fibrinolytic enzyme of S. maltophilia as a thrombolytic agent may be a useful therapeutic adjunct in the future. Further studies are needed to comfirm the results obtained in the present study.