Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection.

BACKGROUND: Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin. METHODS: A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated. RESULTS: The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin. CONCLUSIONS: The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates.

Accessory Gene Regulator (agr) group polymorphisms in methicillin-resistant Staphylococcus aureus and its association with biofilm formation.

 Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main causes of community- and hospital-acquired infections. The expression of virulence genes in S. aureus is arranged by regulators like the accessory gene regulator (agr). The present study aims to estimate phenotypic characteristics of S. aureus and investigate the occurrence of agr genes with their correlation to biofilm formation. In this study, 34 MRSA strains out of 100 S. aureus isolates were recovered in a variety of clinical samples. Phenotypic characterization and ability of biofilm formation were assessed. About 8(24%) of isolates were biofilm producers. The percentages of biofilm production among isolates were 3(37.5%), 2(25%), 3(37.5%) as strong, moderate, and weak, respectively. Furthermore, the resistance rates for all antibiotics were higher in biofilm producers and 76% of the isolates were staphyloxanthin producers, around 82% of the strains showed resistance to H2O2. Hemolytic activity was detected in 74% of the total isolates. The activity of the protease enzyme was 68%. The lipase enzyme was active in 79% of the tested S. aureus isolates. The majority of isolates were established to be agrI 84%, followed by agrII 53%, agrIII 32%, and 30% of the isolates have agr IV. Our study indicated that the majority of MRSA isolates were non-biofilm producers and the agr I is the most dominant type. Thus, agr I is not correlated with biofilm production.

Diversity of biofilm-specific antimicrobial resistance genes in Pseudomonas aeruginosa recovered from various clinical isolates.

Background and Objectives: The resistance of Pseudomonas aeruginosa to antibiotics offers a significant challenge in the treatment of patients. This study aimed to investigate the antimicrobial resistance profile, biofilm-specific antimicrobial resistance genes, and genetic diversity of P. aeruginosa recovered from clinical samples. Materials and Methods: Totally 47 non-duplicate isolates of P. aeruginosa were recovered from various clinical samples. toxA, algD, ndvB, and tssC1 genes were detected in biofilm-producing isolates. The DNA sequences of the toxA and tssC1 genes were analyzed, by creating phylogenetic trees. Results: The findings revealed that 30 (63.8%) of the isolates tested positive for Extended spectrum ß-lactamase (ESBL), whereas 31 (65.9%) tested positive for Metallo-ß-lactamase (MBL) and all of the isolates presented the toxA genes, and 19.1%,17%, 6.3% presented by algD, ndvB and tssC1 genes. Besides, the phylogenetic trees of the toxA and tssC1 gene isolates suggested a genotype that was closely aligned with others. Gene sequencing similarity revealed 99% identity with other isolates deposited in GenBank. Conclusion: The occurrence of toxA was most prevalent. One isolate was recorded as a novel isolate in the global gene bank as a locally isolated strain from the city of Erbil that has never been identified in global isolates due to genetic variation.

Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC)

PURPOSE: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients. PATIENTS: Patients (n = 54) with locally inoperable or distant metastasis and performance status of 0-2 were eligible. The triplet combination chemotherapy consisting of docetaxel 60 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and 5-fluorouracil 600 mg/m(2) for 5 days of continuous infusion were administered every 21 days, up to nine cycles. Prophylactic G-CSF was not allowed. RESULTS: In all, 36 (67 %) patients were male and 18 (33 %) were female; median age was 59 years. The majority of patients (n = 46, 85 %) had metastatic disease and 8 (15 %) of them had locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (43 %) and 18 (39 %) of the 46 cases, respectively. The median cycle of chemotherapy was 6. In assessing 50 patients for response evaluation, one had complete response. Partial response was achieved in 27 (54 %) patients. Seventeen patients (34 %) had stable disease and 5 (10 %) had progressive disease, while 4 % (n = 2) and 11 % (n = 6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. During the median follow-up time (6.9 months, range 0.4-24), 28 (52 %) patients died. The overall and progression-free survival were 10.7 [95 % CI 8.9-12.4] and 6.8 [95 % CI 5.8-7.8] months, respectively. CONCLUSIONS: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects (AU)

Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC).

PURPOSE: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients. PATIENTS: Patients (n = 54) with locally inoperable or distant metastasis and performance status of 0-2 were eligible. The triplet combination chemotherapy consisting of docetaxel 60 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and 5-fluorouracil 600 mg/m(2) for 5 days of continuous infusion were administered every 21 days, up to nine cycles. Prophylactic G-CSF was not allowed. RESULTS: In all, 36 (67 %) patients were male and 18 (33 %) were female; median age was 59 years. The majority of patients (n = 46, 85 %) had metastatic disease and 8 (15 %) of them had locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (43 %) and 18 (39 %) of the 46 cases, respectively. The median cycle of chemotherapy was 6. In assessing 50 patients for response evaluation, one had complete response. Partial response was achieved in 27 (54 %) patients. Seventeen patients (34 %) had stable disease and 5 (10 %) had progressive disease, while 4 % (n = 2) and 11 % (n = 6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. During the median follow-up time (6.9 months, range 0.4-24), 28 (52 %) patients died. The overall and progression-free survival were 10.7 [95 % CI 8.9-12.4] and 6.8 [95 % CI 5.8-7.8] months, respectively. CONCLUSIONS: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects.

Prognostic significance of the metastatic lymph node ratio for survival in colon cancer.

PURPOSE: The metastatic lymph node ratio (LNR) is defined as the number of metastatic lymph nodes divided by the total number of lymph nodes removed. The aim of this study was to investigate the prognostic significance of the metastatic LNR in patients with colon cancer. METHODS: One-hundred twenty-five patients with stage III colon cancer admitted to the Istanbul University Oncology Institute between 1995 and 2005 were retrospectively evaluated. The median LNR was 0.2, and this figure was accepted as cut-off value in the present study. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. Log-rank test was used for intergroup comparisons. The significance level was put at p<0.05. RESULTS: Of the 125 patients, 58 (46.4%) were males and 67 (53.6%) females with median age 57 years. The mean OS in patients with a LNR <0.2 was 120.5±7.3 months, with a LNR ≥0.2 was 92.8±9.0 months Although clinically significant, the difference between the groups was statistically insignificant (p=0.074). The mean duration of DFS in patients with a LNR <0.2 was 100.6±8.6 months and for those with a LNR ≥0.2 it was 71.7±8.3 months (p=0.017). The 5-year DFS rate in patients with a LNR ≥0.2 was 42.3%; it was 64.1% in those with LNR<0.2. The difference between the groups was statistically significant (p=0.017). CONCLUSION: The determination of the optimal cut-off value for the LNR in future prospective studies will help defining prognosis with better accuracy in colon cancer patients.

Identification of a shine-through artifact in the trachea with (124)I PET/CT.

UNLABELLED: The presence of (124)I in tissue near the trachea can cause a phenomenon that might be called shine-through. The effect is due to high-energy positrons that cross the air-filled trachea and annihilate at the opposite tracheal wall, incorrectly suggesting uptake at that location. METHODS: We investigated shine-through using (124)I, (68)Ga, and (18)F PET/CT scans of a neck phantom. Additionally, we evaluated (124)I studies of 29 patients with differentiated thyroid cancer who underwent imaging for postsurgical staging. RESULTS: In the phantom studies with a 0.1-mL (124)I source, the relative intensity of shine-through decreased from 7% to nearly zero when the thickness of the positron-stopping layer was increased from 0.3 to 3.85 mm. In patients, shine-through was observed in 5 of the 29 studies, with intensities between 0.7% and 14%. CONCLUSION: Shine-through appears rather common in differentiated thyroid cancer. Recognition is important for identification of real lesions, calculation of uptake, and dosimetry.

Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer.

In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis.

Adjuvant chemoradiation for patients with adenocarcinoma of the pancreas: an expirence of single institute.

Only a small percentage of patients with pancreatic cancer have limited disease suitable for curative resection. Even with surgery, patients often have poor long-term survival due to relapse of the disease. There are controversies about the adjuvant treatment of these patients. We reported the survival of resected pancreatic cancer from a single institute. About 128 consecutive patients who had complete resection of the pancreatic ductal adenocarcinoma were evaluated, retrospectively. Chemoradiotherapy (45 Gy plus 5-fluorouracil) was given to 63 patients. Fifty-five patients declined to take chemoradiotherapy or with poor performance status were observed without additional treatment. Eight patients took only chemotherapy and two patients took only radiotherapy. The median survival of chemoradiotherapy group was significantly higher than the observation group (13 months vs. 4 months, respectively; P < 0.001). In multivariate analyses the most important factors improving survival were the application of chemoradiation (P < 0.001), low-level serum LDH (P = 0.026), good performance status (P = 0.033) and low serum CA19-9 (P = 0.037). Although adjuvant chemoradiotherapy has a significant survival benefit when compared with the observation group, the survival data are still poor for pancreatic cancer. Therefore, we need more effective additional or adjuvant treatment modalities.

XELOX followed by XELIRI or the reverse sequence in advanced colorectal cancer.

BACKGROUND: Capecitabine has demonstrated high efficacy as first-line treatment for metastatic colorectal cancer (mCRC). In this non-randomized pilot study, we investigated the efficacy and safety of sequentially administered XELOX and XELIRI regimens or the reverse sequence in patients with advanced colorectal cancer. PATIENTS AND METHODS: Entry criteria were histologically confirmed mCRC, ECOG performance status (PS) < or =2 and adequate bone marrow, renal and hepatic function. All patients consecutively received XELOX followed by XELIRI at disease progression or vice versa. RESULTS: In multivariate analysis, independent prognostic factors with worse overall survival were: lower PS (p = 0.0001), multiple metastatic sites (p = 0.016) and high tumor grade. Higher serum levels of alkaline phosphatase and worse ECOG PS were associated with a shorter progression-free survival. Grade 3/4 mucositis, nausea/vomiting, grade 3/4 alopecia and grade 3 diarrhea were more frequent with XELIRI, whereas major toxicity events with XELOX were grade 3 neutropenia, thrombocytopenia and grade 2/3 neurotoxicity. CONCLUSION: Capecitabine appears to be an acceptable alternative to continuous-infusion fluorouracil (FU)/leucovorin (LV) in combination therapy and offers an effective, but more convenient alternative to continuous infusion FU/LV in the first-line treatment of patients with mCRC.

Value of glutathion-S transferase pi as a prognostic factor in epithelial ovarian carcinoma.

The association between glutathione S-transferase pi (GSTpi) and other clinicopathological parameters, response to chemotherapy and clinical outcome were investigated in chemotherapy naive epithelial ovarian cancer patients. Paraffin-embedded material from 55 patients were used for immunohistochemical analysis. All patients had received six cycles of cisplatinum-based chemotherapy and 41 of them were revalued by laparotomy. Pre- and post-chemotherapy GSTpi staining were detected in the cancer tissues of 18/55 (32.7%) and 5/14 (35.7%) patients, respectively. GSTpi expression was not associated with other clinicopathologic parameters. Of 17 patients with postoperative measurable residual disease clinical response was observed in 4/7 of GSTpi positive and in 9/10 GSTpi negative patients (p = 0.25). Pathologic complete response (pCR) was achieved in 5/8 of GSTpi positive and 11/22 of GSTpi negative cases (p = 0.69). There was no significant difference in overall survival and progression-free survival (PFS) according to initial GSTpi status. However the PFS of the five patients (median 22 +/- 5.9 months) who had postchemotherapy positive GSTpi was significantly shorter than the nine patients (10.0 +/- 2.19 months) who had negative GSTpi (p = 0.006). This difference was not observed in overall survival. These results suggest that initial immunohistochemical staining of GSTpi does not aid in the prediction of pCR and clinical outcome in patients with epithelial ovarian cancer. Nonetheless investigation of GSTpi expression after chemotherapy needs further evaluation.

Prognostic factors and survival in patients with metastatic or recurrent carcinoma of the uterine cervix.

The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment. Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval ( 8 months vs.

Efficacy of cisplatin and cyclophosphamide combination for recurrent and metastatic carcinoma of the uterine cervix.

The efficacy of a combination of cyclophosphamide and cisplatin in patients with metastatic and recurrent carcinoma of the cervix, was tested. Thirty patients were included in the study. Initially, 27 patients (90%) had received pelvic radiation and intracavitary boost and one patient was additionally given paraaortic radiation. Cisplatin was given at 75 mg/m2 followed by cyclophosphamide at 750 mg/m2 on day 1 with three weekly intervals for a maximum of six cycles. All patients received a median of four cycles of chemotherapy. The overall response rate for all eligible patients was 20% (continuous CR: 1, CR: 1, PR: 4 patients). Overall response rate and progressive response in patients with relapse within the previous radiation field were 9.5% and 66.7%, respectively; while for patients who had recurrent disease outside any irradiated area both were 44.4%. Eighteen patients (60%) had early withdrawal from the planned schedule, which was due to patient incompliance in seven patients (23.3%), disease progression in ten (33.3%) and early death after the first cycle in one patient (3.3%). Anemia was the most frequent toxicity, necessiating 24 transfusions in nine patients (30%). WHO grade 3 and 4 toxicity were anemia: 13 (43.3%), leucopenia: one (3.3%), thrombocytopenia: two (6.6%), renal: one, emesis: nine (30.0%) patients. The median survival duration for all eligible patients was 11 months. Univariate analysis revealed that progressive response to chemotherapy was the only prognostic factor for survival (7.1 vs 16.8 months, p = 0.003). The combination of cisplatin and cyclophosphamide did not appear to be more active than single agent cisplatin in this patient group with a relatively poor prognosis. Further studies are required to determine a better therapeutic approach for patients with relapsed carcinoma of the cervix.

A phase II study of paclitaxel and cisplatin combination chemotherapy in recurrent or metastatic head and neck cancer.

The taxanes are the most active new agents for squamous-cell carcinoma of the head and neck (SCCHN) since the discovery of cisplatin. Our aim was to define the therapeutic efficacy and toxicity of paclitaxel and cisplatin combination therapy in patients with recurrent SCCHN. Patients with locally recurrent or metastatic SCCHN were enrolled in the study. Patients were required to be chemotherapy-naive, and should have completed radiation therapy at least 6 weeks prior to enrollment. A World Health Organization (WHO) performance status of less than 3 was required. Paclitaxel (Taxol, Bristol Myers Squibb Company, Princeton, NJ) and cisplatin therapy (PC) consisted of prophylaxis with pheniramine 50 mg i.v., ranitidine 150 mg i.v. and dexamethasone 20 mg i.v. given prior to paclitaxel 175 mg/m2 as a 3-hour i.v. infusion, followed by cisplatin 75 mg/m2 as a 1-hour infusion with an additional 3000 cc of saline for hydration. This treatment was repeated every 3 weeks for a maximum of six cycles. Patients were evaluated for response after the third and sixth cycles, or at the time of clinical progression. Fifty patients were enrolled in the study. The overall response rate was 32% with a 10% complete response rate. Forty-eight patients were assessable for toxicity. A total of 221 cycles of chemotherapy was given and the most common toxicity was myelosuppression; 7.7% of cycles had grade III-IV neutropenia. Severe neuropathy, nephropathy, mucositis, and emesis were uncommon (<10 %). At a median follow-up period of 25 months, the median overall survival was 10 months and the 1-year progression-free and overall survival rates were 16.7% and 35.2%, respectively. We conclude that patients with recurrent SCCHN have a moderate response to combination chemotherapy with cisplatin and paclitaxel. Given this moderate response rate, it is unlikely that this combination (PC) might ultimately prove to be superior to standard treatment regimens in terms of significant survival advantage.

Treatment of aggressive non-Hodgkin's lymphoma with dose-intensified epirubicin in combination of cyclophosphamide, vincristine, and prednisone (CEOP-100): a phase II study.

Epirubicin is an agent with a lower incidence of cardiotoxicity and myelotoxicity compared with doxorubicin; and it is active in patients with non-Hodgkin's lymphoma (NHL). Our aim was to define the therapeutic efficacy and toxicity of dose-intensified epirubicin in combination with cyclophosphamide, vincristine, and prednisone (CEOP) in patients with diffuse large-cell NHL. Previously untreated patients aged between 15 and 75 years, with at least one measurable lesion, adequate liver, renal, cardiac functions, and no central nervous system involvement were included in the study. The planned chemotherapy regimen CEOP consisted of cyclophosphamide 750 mg/m2, epirubicin 100 mg/m2, and vincristine 1.4 mg/m2 intravenously on day 1 and 100 mg prednisone taken orally on days 1 to 5. Courses were repeated every 21 days. Patients with stage I and II received four cycles of chemotherapy followed by involved-field radiotherapy, and patients with stage III and IV received six cycles of chemotherapy followed by radiotherapy to bulky lymph node sites. Seventy-five patients were enrolled in the study. The complete response rate was 83.8%, and 72 patients were assessable for toxicity. The most common toxicity was myelosuppression; 13.9% of the patients had grade III-IV neutropenia. Severe mucositis, diarrhea, and emesis were uncommon (<10%). At a median follow-up period of 41 months, the 5-year progression-free survival and overall survival rates were 63.5% and 65.3%, respectively. Increasing the dose intensity of epirubicin can yield a similar complete response rate compared with the regimens used in NHL without significantly increasing the toxicity rate associated with chemotherapy. The role of dose-intensive epirubicin should be investigated further in future randomized trials.