Staphylococcus Aureus colonization and bacteremia in children with cancer.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3666-3666
Author(s):  
Ashok Srinivasan ◽  
Steven Seifried ◽  
Liang Zhu ◽  
Deo Kumar Srivastava ◽  
Matthew Bankowski ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Conflicts Of Interest ◽  
Methicillin Resistance ◽  
Healthy Children ◽  
Children With Cancer ◽  
Spa Typing ◽  
Patients With Cancer ◽  
Number Of Patients ◽  
Increased Risk ◽  
Rectal Colonization

Abstract Abstract 3666 Poster Board III-602 Background Staphylococcus aureus is an important cause of blood stream infections in children and adults. In recent years, new strains of methicillin-resistant S. aureus (MRSA), also known as community-acquired (CA)-MRSA have been isolated from otherwise healthy individuals. These strains frequently carry the Panton-Valentine Leukocidin (PVL) leukotoxin and belong to spa type 8; USA300 genotype, which is the most common strain causing CA-MRSA infections in the U.S. The clinical course of infections with PVL-positive S.aureus strains appears to be more severe than infection from PVL-negative strains. Bacteremia due to these strains has been reported in children, adolescents and adults. It is not known if methcillin-resistance or infection with CA-MRSA strains adversely affects outcome in children with cancer. Colonization of MRSA in healthy children has increased significantly since 2001 and has shown to be a risk factor for subsequent infection. However the prevalence of nasal and rectal colonization with MRSA; in particular with PVL-positive strains and the relationship between colonization and infection is not known in children or adults with cancer. Methods The epidemiology of MRSA and methicillin-sensitive S.aureus (MSSA) bacteremia and prevalence of MRSA nasal and rectal colonization in children with cancer was retrospectively studied from 2000 to 2007. Medical record review included patient demographics, underlying disease and antimicrobial susceptibility patterns of the MRSA and MSSA bacteremia isolates. Molecular typing was performed by polymerase chain reaction (PCR) on all isolates for detection of the PVL genes. Staphylococcus cassette chromosome (SCC) mec and spa typing was performed on all PVL-positive MRSA and MSSA bacteremia isolates and MRSA isolates causing colonization and infection. Demographic and treatment variables were compared between patients with MRSA and MSSA bacteremia and patients with PVL-positive and PVL-negative MRSA and MSSA bacteremia using exact two-sample Wilcoxon rank sum test or robust rank sum test for unequal variances and Fisher's exact chi-square test. The trend of MRSA/MSSA bacteremia and MRSA colonization was evaluated by logistic regression models. Results Ten (19%) MRSA and 42 (81%) MSSA isolates from clinically distinct infectious bacteremic episodes were collected from 52 patients with cancer during the eight year study period. The proportion of cancer patients with MRSA, or MSSA bacteremia did not change significantly over the duration of the study. A third of the patients, 17 (33%), had complications. Thirty-eight (73%) of the bacteremic episodes were catheter-related. Catheters were removed significantly more often for MRSA infections than for MSSA infections for persistently positive blood cultures or complications (p=0.003). Subcutaneous ports was removed significantly more often than Hickman catheters (p= 0.005). The number of patients with persistently positive MRSA bacteremia were higher as compared to MSSA bacteremia (p= 0.004). Methicillin resistance was associated with decreased susceptibility to erythromycin (p=0.0003) and gentamicin (p=0.03). The difference in PVL positivity between MRSA and MSSA was statistically significant (P=0.01). None of the other variables studied including complications were significantly different between patients with MRSA or MSSA bacteremia or between patients with PVL-positive and PVL-negative S.aureus bacteremia. The number of patients colonized with MRSA compared to the total number of samples tested increased significantly between 2000-2001 and 2006-2007 (p=0.0007). PVL-positivity was associated both with increased colonization (p=0.004) and with an increased risk of infection (p=0.0005). There was a discordance in the spa types between the colonization and infection isolates. Conclusions This report represents the first description of the epidemiology of S.aureus bacteremia and colonization including analysis of PVL-positive strains in children with cancer. Methicillin-resistance or PVL-positivity did not appear to be associated with a worse outcome in our patient population. The number of patients colonized with MRSA increased significantly during this time period. PVL-positivity was associated with an increased risk of colonization and infection. Further studies are needed to confirm these observations in patients with cancer. Disclosures: No relevant conflicts of interest to declare.

Thrombo-Embolism in Patients Receiving Erythropoeitic Stimulating Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4005-4005
Author(s):  
Donald Doll
Keyword(s):  
Pulmonary Embolism ◽  
Cancer Patients ◽  
Conflicts Of Interest ◽  
Central Catheter ◽  
Label Change ◽  
Patients With Cancer ◽  
Catheter Occlusion ◽  
Time Period ◽  
Number Of Patients ◽  
Increased Risk

Abstract 4005 Poster Board III-941 Background There is an increased risk of thrombo-embolism in patients receiving erythropoeitic stimulating agents (ESAs) in the treatment of anemia due to cancer and chemotherapy as well as in patients with chronic renal failure. This fact coupled with evidence of the negative impact on survival in some patients with cancer has prompted a change in the FDA label and restricted the use of ESAs. The exact incidence of thrombo-embolism etiologically related to ESAs in community cancer practices is not known. In this retrospective study we examined the relationship between the administration of ESAs and thrombo-embolism in patients treated after initiating the more conservative use of such agents based on label change. Methods One-hundred fifty-eight cases of thrombo-embolism and central catheter occlusion observed between August 2007 and May 2009 were identified through the electronic medical records (EMR) database at Gabrail Cancer Center. Likewise, all patients who received ESAs during the same time period were identified through the EMR. Records of all patients were examined to verify diagnosis, confirm data, and validate timing of administration of the ESAs. Results A total of 496 patients received ESAs during the study period. Of these patients, 158 developed thrombo-embolism or central catheter occlusion. There were 128 patients with cancer and 34 had non-cancerous diagnoses with mean age of 62 and M:F of 4:1. Of the 128 patients with cancer 99 patients developed uncomplicated catheter occlusion and 39 developed DVT and/or pulmonary embolism. Seventy-four of the 99 patients who had catheter occlusion had received ESAs (74%). Of the 39 patients who developed DVT and pulmonary embolism 26 were treated with ESAs (67%). Of the 99 patients who developed catheter occlusion 51 (51%) received ESAs prior to catheter occlusion of the 39 patients who had DVT and PE 19 (48%) of the events happened after ESAs were initiated. The total number of patients who received ESAs during the same time period was 496. Only 32% of these patients developed thrombo-embolism and catheter occlusion. However, only 114 patients (23%) experienced a thrombotic episode after ESAs were initiated. This did not differ significantly from the incidence of thrombosis either in the form of catheter occlusion, deep vein thrombosis, or pulmonary embolism in this patient population. Conclusion Although some studies have shown an increased incidence of thromboembolism in cancer patients receiving ESAs, such studies were performed at a time when the use of these agents was more liberal in order to increase the Hb to normal or above normal levels. In this community-based practice study that included patients treated after the label change, the incidence was not greater than that seen in cancer patients not receiving ESAs. However, a prospective clinical trial is needed to confirm these findings especially after the label change that has restricted the use of ESAs. 3(Transmittal 80, Pub 100-03 Medicare National Coverage Decision, eff. 7/30/2007) Disclosures: No relevant conflicts of interest to declare.

scholarly journals The First Report of a Methicillin-Resistant Staphylococcus aureus Isolate Harboring Type IV SCCmec in Thailand

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 430
Author(s):  
Wichai Santimaleeworagun ◽  
Praewdow Preechachuawong ◽  
Wandee Samret ◽  
Tossawan Jitwasinkul
Keyword(s):  
Staphylococcus Aureus ◽  
Resistance Genes ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Sccmec Type ◽  
Clinical Strain ◽  
Spa Typing ◽  
Methicillin Resistant ◽  
Type Iv ◽  
Antimicrobial Resistance Genes

Methicillin-resistant Staphylococcus aureus (MRSA) is mostly found in Thailand in the hospital as a nosocomial pathogen. This study aimed to report the genetic characterization of a clinical community-acquired MRSA (CA-MRSA) isolate collected from hospitalized patients in Thailand. Among 26 MRSA isolates, S. aureus no. S17 preliminarily displayed the presence of a staphylococcal cassette chromosome mec (SCCmec) type IV pattern. The bacterial genomic DNA was subjected to whole-genome sequencing. Panton–Valentine leukocidin (PVL) production, virulence toxins, and antibiotic resistance genes were identified, and multi-locus sequence typing (MLST) and spa typing were performed. The strain was matched by sequence to MLST type 2885 and spa type t13880. This strain carried type IV SCCmec with no PVL production. Five acquired antimicrobial resistance genes, namely blaZ, mecA, Inu(A), tet(K), and dfrG conferring resistance to β-lactams, lincosamides, tetracycline, and trimethoprim, were identified. The detected toxins were exfoliative toxin A, gamma-hemolysin, leukocidin D, and leukocidin E. Moreover, there were differences in seven regions in CR-MRSA no. S17 compared to CA-MRSA type 300. In summary, we have reported the ST2885-SCCmec IV CA-MRSA clinical strain in Thailand for the first time, highlighting the problem of methicillin resistance in community settings and the consideration in choosing appropriate antibiotic therapy.

scholarly journals P54 Pneumocystis jirovecii prophylaxis in patients on rituximab

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Kishore Warrier1 ◽  
Catherine Salvesani ◽  
Samundeeswari Deepak
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Pneumocystis Jirovecii ◽  
Current Evidence ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.

scholarly journals Impact of mass administration of azithromycin as a preventive treatment on the prevalence and resistance of nasopharyngeal carriage of Staphylococcus aureus

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0257190
Author(s):  
Soumeya Hema-Ouangraoua ◽  
Juliette Tranchot-Diallo ◽  
Issaka Zongo ◽  
Nongodo Firmin Kabore ◽  
Frédéric Nikièma ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Respiratory Infections ◽  
Methicillin Resistance ◽  
Pediatric Population ◽  
Preventive Treatment ◽  
Nasal Carriage ◽  
Post Intervention ◽  
Serious Illness ◽  
Increased Risk ◽  
The Impact

Staphylococcus aureus is a major cause of serious illness and death in children, indicating the need to monitor prevalent strains, particularly in the vulnerable pediatric population. Nasal carriage of S. aureus is important as carriers have an increased risk of serious illness due to systemic invasion by this pathogen and can transmit the infection. Recent studies have demonstrated the effectiveness of azithromycin in reducing the prevalence of nasopharyngeal carrying of pneumococci, which are often implicated in respiratory infections in children. However, very few studies of the impact of azithromycin on staphylococci have been undertaken. During a clinical trial under taken in 2016, nasal swabs were collected from 778 children aged 3 to 59 months including 385 children who were swabbed before administration of azithromycin or placebo and 393 after administration of azithromycin or placebo. Azithromycin was given in a dose of 100 mg for three days, together with the antimalarials sulfadoxine-pyrimethamine and amodiaquine, on four occasions at monthly intervals during the malaria transmission season. These samples were cultured for S. aureus as well as for the pneumococcus. The S. aureus isolates were tested for their susceptibility to azithromycin (15 g), penicillin (10 IU), and cefoxitine (30 g) (Oxoid Ltd). S. aureus was isolated from 13.77% (53/385) swabs before administration of azithromycin and from 20.10% (79/393) six months after administration (PR = 1.46 [1.06; 2.01], p = 0.020). Azithromycin resistance found in isolates of S. aureus did not differ significantly before and after intervention (26.42% [14/53] vs 16.46% [13/79], (PR = 0.62 [0.32; 1.23], p = 0.172). Penicillin resistance was very pronounced, 88.68% and 96.20% in pre-intervention and in post-intervention isolates respectively, but very little Methicillin Resistance (MRSA) was detected (2 cases before and 2 cases after intervention). Monitoring antibiotic resistance in S. aureus and other bacteria is especially important in Burkina Faso due to unregulated consumption of antibiotics putting children and others at risk.

scholarly journals Nasopharyngeal carriage, spa types and drug susceptibility profiles of Staphylococcus aureus from healthy children under 5 years in eastern Uganda

2019 ◽  
Author(s):  
David Kateete ◽  
Benon B Asiimwe ◽  
Raymond Mayanja ◽  
Brian Mujuni ◽  
Freddie Bwanga ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Low Income ◽  
Pulse Field ◽  
Healthy Children ◽  
Beta Lactam ◽  
Spa Typing ◽  
Carriage Rate ◽  
Eastern Uganda ◽  
Spa Types ◽  
Children Under 5

Abstract Background Staphylococcus aureus carriage is a known risk factor for staphylococcal disease. However, the carriage rates vary by country, demographic group, etc. This study aimed to determine the S. aureus carriage rate in Ugandan children, and track Staphylococcus strains that can cause infection in Uganda. Methods Nasopharyngeal samples (one per child) from 742 healthy children under 5 years living in Iganga/Mayuge Health & Demographic Surveillance Site in eastern Uganda were processed for isolation of S. aureus. Genotyping was performed by spa typing and pulse field gel electrophoresis. Results The processed samples yielded 144 S. aureus isolates (one per sample/child) therefore, the S. aureus carriage rate in the children was 19.4% (144/742). Further, 45 (31.3%, 45/144) of the isolates were methicillin resistant (MRSA) yielding a carriage rate of 6.1% (45/742). All MRSA isolates were susceptible to vancomycin, linezolid and clindamycin however, compared to methicillin susceptible S. aureus (MSSA) isolates (68.8%, 99/144), MRSA were more resistant to non-beta-lactam antimicrobials –tetracycline (91.1%, 41/45), trimethoprim/sulfamethoxazole (73.3%, 33/45), erythromycin (75.6%, 34/99), chloramphenicol (60%, 19/99), gentamicin (55.6%, 25/45) and ciprofloxacin (35.6%, 16/45). Furthermore, an MRSA isolate was mupirocin resistant and 42 (93.3%, 42/45) were multidrug resistant (MDR); three (3%, 3/99) MSSA isolates were mupirocin and clindamycin resistant while 61 (61.6%, 61/99) were MDR. All MSSA/MRSA isolates were susceptible to rifampicin, vancomycin and linezolid but only two were pan-susceptible to the tested antibiotics. Seven spa types were detected in MRSA, of which t064 & t037 were predominant and associated with SCCmec types I & IV, respectively. Fourteen spa types were detected in MSSA, of which t645 & t4353 were predominant. Conclusions S. aureus (MSSA/MRSA) carriage rate in children in rural eastern Uganda is high and comparable to rates for hospitalized patients in Kampala city. Detection of mupirocin resistance is worrying as it could rapidly increase in a low-income setting should mupirocin be used for staphylococcal decolonization. Further, S. aureus strains of spa types t064, t037, t645 & t4353 are prevalent and could be responsible for majority of staphylococcal infections in Uganda.

scholarly journals P24 Can high ANA titre combined with clinical features predict developing autoimmune conditions in children?

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Ovgu Kul Cinar ◽  
Charlene Foley ◽  
Ali Al-Hussaini ◽  
Kimberly Gilmour ◽  
Matthew Buckland ◽  
...  
Keyword(s):  
Clinical Features ◽  
Chart Review ◽  
Conflicts Of Interest ◽  
Connective Tissue Diseases ◽  
Retrospective Chart Review ◽  
Final Diagnosis ◽  
Healthy Children ◽  
Street Hospital ◽  
Increased Risk ◽  
Autoimmune Conditions

Poster presentation Tuesday 8 October Background Antinuclear antibodies (ANA) are autoantibodies that recognise cellular antigens found predominantly in the cell nucleus. They are associated with numerous autoimmune diseases such as systemic lupus erythematosus, but may also be found in infectious diseases, malignancies and healthy individuals. ANA is requested as part of an initial work-up for autoimmune conditions. In healthy children (5-18%), positive ANA titres of 1/80 to 1/320 have been reported. A prospective study of healthy children with positive ANA found that children who developed autoimmune disease had clinical features at presentation that were suspicious for such an outcome. Therefore, the usefulness of a positive ANA result for diagnosing autoimmune conditions is limited without clinical correlation. The aim of our study was to assess whether high ANA titre and clinical features at presentation could predict final diagnosis. Methods Single centre retrospective study at Great Ormond Street Hospital for Children (GOSH). The immunology laboratory provided a list of positive ANA results (using indirect immunofluorescence technique) from January 2013 to July 2018. A retrospective chart review was performed to ascertain presence of clinical features at presentation under the five following titles: arthritis, skin involvement, eyes, CNS involvement and Raynaud’s phenomenon. We then reviewed the last clinical contact to document confirmed diagnosis. Results We performed a retrospective chart review on 1,354 children (67% female; median age 7.5 years (0.1-17.5); median follow-up 4.8 years (0-18)) with positive ANA results (titres 1/160, 1/320, 1/640, 1/1280, 1/2560 and >1/2560). Table 1 reports ANA titres at first presentation in relation to final diagnosis. A titre of 1/640 or above was most commonly seen (>50%) in children with an autoimmune rheumatology condition. In fact, children with the highest titre (>1:2560) were significantly more likely to be diagnosed with one of these conditions. Finally, we looked at the number of presenting features and correlated with final diagnosis. Those diagnosed with a CTD were most likely to present with 2-5 clinical features (p < 0.0001). P24 Table 1: Percentage of patients grouped according to their diagnosis and ANA titres Final Diagnoses ANA Titres >1: 2560 1: 2560 1: 1280 1: 640 1: 320 1: 160 Connective Tissue Diseases 24% 9% 13% 16% 16% 22% JIA and Uveitis 8% 11% 15% 22% 22% 22% JIA 6% 8% 13% 24% 24% 25% Autoimmune (other) 4% 5% 11% 19% 32% 29% Unidentified autoimmune/ autoinflammatory 8% 12% - 24% 12% 44% Vasculitis - - 5% 26% 16% 53% Sarcoidosis - 20% - 20% - 60% Autoinflammatory 7% - - 43% - 50% Malignancy - - - 25% - 75% Other 3% 2% 3% 17% 28% 47% Non-inflammatory MSK 3% - 9% 18% 27% 43% Conclusion This study suggests that, patients presenting with higher ANA titres and a combination of clinical features should be assessed systemically and followed-up as they may have increased risk of developing an autoimmune rheumatological conditions. Conflicts of Interest The authors declare no conflicts of interest.

scholarly journals Increasing prevalence of nasal and rectal colonization with methicillin-resistant Staphylococcus aureus in children with cancer

2010 ◽  
Vol 55 (7) ◽  
pp. 1317-1322 ◽  
Author(s):  
Ashok Srinivasan ◽  
Steven E. Seifried ◽  
Liang Zhu ◽  
Deo K. Srivastava ◽  
Rosalie Perkins ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Children With Cancer ◽  
Methicillin Resistant ◽  
Rectal Colonization

scholarly journals Prevalence of methicillin resistance and superantigenic toxins in Staphylococcus aureus strains isolated from patients with cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Effat Abbasi Montazeri ◽  
Azar Dokht Khosravi ◽  
Saeedeh Khazaei ◽  
Ali Sabbagh
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Cancer Patients ◽  
Methicillin Resistance ◽  
Resistance Pattern ◽  
Patients With Cancer ◽  
Resistance Patterns ◽  
Mrsa Strains ◽  
Southwest Iran ◽  
Antibiotic Resistance Patterns

Abstract Background This study aimed to determine the frequency of methicillin-resistant Staphylococcus aureus (MRSA), antibiotic resistance patterns, superantigenic toxins profile, and clonality of this pathogen in patients with cancer. Results In total, 79 (25.7%) isolates were confirmed as Staphylococcus species, from which 38 (48.1%) isolates were S. aureus, and 29 (76.3%) isolates were confirmed as MRSA. The highest resistance in MRSA strains was seen against ciprofloxacin (86.2%) and erythromycin (82.8%). Teicoplanin, and linezolid were the most effective antibiotics. From all MRSA isolates, 3 strains (10.3%) were resistant to vancomycin with minimum inhibitory concentration values of 128 μg/ml. The prevalence of superantigenic toxins genes was as follows: pvl (10.5%), tsst-1 (36.8%), etA (23.7%), and etB (23.7%). The t14870 spa type with frequency of 39.5% was the most prevalent clone type circulating in the cancer patients. Conclusions This study showed the circulating of spa t14870 as the most predominant MRSA clone in cancer patients of southwest Iran. Also, a diverse antibiotic resistance pattern and toxin profiles were seen among MRSA isolates.

scholarly journals Nasopharyngeal carriage, spa types and antibiotic susceptibility profiles of Staphylococcus aureus from healthy children less than 5 years in Eastern Uganda

2019 ◽  
Author(s):  
David Kateete ◽  
Benon B Asiimwe ◽  
Raymond Mayanja ◽  
Brian Mujuni ◽  
Freddie Bwanga ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Low Income ◽  
Antibiotic Susceptibility ◽  
Multidrug Resistant ◽  
Healthy Children ◽  
Beta Lactam ◽  
Spa Typing ◽  
Carriage Rate ◽  
Eastern Uganda ◽  
Spa Types

Abstract Background: Staphylococcus aureus carriage is a known risk factor for staphylococcal disease. However, the carriage rates vary by country, demographic group and profession. This study aimed to determine the S. aureus carriage rate in children in Eastern Uganda, and identify S. aureus lineages that cause infection in Uganda. Methods: Nasopharyngeal samples from 742 healthy children less than 5 years residing in the Iganga/Mayuge Health & Demographic Surveillance Site in Eastern Uganda were processed for isolation of S. aureus. Antibiotic susceptibility testing based on minimum inhibitory concentrations (MICs) was determined by the BD PhoenixTM system. Genotyping was performed by spa typing. Results: The processed samples yielded 144 S. aureus isolates (one per child) therefore, the S. aureus carriage rate in children was 19.4% (144/742). Thirty one percent (45/144) of the isolates were methicillin resistant (MRSA) yielding a carriage rate of 6.1% (45/742). All isolates were susceptible to rifampicin, vancomycin and linezolid. Moreover, all MRSA were susceptible to vancomycin, linezolid and clindamycin. Compared to methicillin susceptible S. aureus (MSSA) isolates (68.8%, 99/144), MRSA isolates were more resistant to non-beta-lactam antimicrobials –trimethoprim/sulfamethoxazole 73.3% (33/45) vs. 27.3% (27/99) [P<0.0001]; erythromycin 75.6% (34/45) vs. 24.2% (24/99) [P<0.0001]; chloramphenicol 60% (27/45) vs. 19.2% (19/99) [P<0.0001]; gentamicin 55.6% (25/45) vs. 25.3% (25/99) [P=0.0004]; and ciprofloxacin 35.6% (16/45) vs. 2% (2/99) [P<0.0001]. Furthermore, 42 MRSA (93.3%) were multidrug resistant (MDR) and one exhibited high-level resistance to mupirocin. Overall, 61 MSSA (61.6%) were MDR, including three mupirocin and clindamycin resistant isolates. Seven spa types were detected in MRSA, of which t037 & t064 were predominant and associated with SCCmec types I & IV, respectively. Fourteen spa types were detected in MSSA, of which t645 & t4353 were predominant. Conclusions: S. aureus carriage rate in healthy children in Eastern Uganda is high and comparable to rates for hospitalized patients in Kampala. The detection of mupirocin resistance is worrying as it could rapidly increase if mupirocin is administered in a low-income setting. S. aureus strains of spa types t064, t037 (MRSA) and t645, t4353 (MSSA) are prevalent and could be responsible for majority of staphylococcal infections in Uganda.

scholarly journals Increase in Mortality and Second Neoplasms in Chronic Lymphocytic Leukemia with Pro/Pro Genotype of TP53 Codon 72

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Martin Cabero-Becerra ◽  
Jose Antonio Garcia Vela ◽  
Pedro Sanchez-Godoy ◽  
Angel Arias-Arias ◽  
Miguel Piris-Villaespesa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tp53 Mutation ◽  
Conflicts Of Interest ◽  
The Other ◽  
Complex Karyotype ◽  
Codon 72 ◽  
Risk Of Death ◽  
Second Neoplasms ◽  
Number Of Patients ◽  
Increased Risk

Chronic Lymphocytic Lymphoma (CLL) is a heterogeneous disease in which many important factors for its prognosis have been identified. The normal functioning of p53 is one of the most critical barriers against cancer; therefore, if it has a deletion and/or mutation, it is a robust biomarker for the therapeutic response in CLL. The possibility was raised that some germline single - nucleotide polymorphisms of TP53 in healthy populations may also affect p53 function. One of the most studied polymorphisms of the TP53 gene is codon 72 in exon 4, a CGC to CCC transition (R72P), due to its potential effect on cancer risk. As with many types of cancer, its association with a worse prognosis in CLL is unclear. We analyzed the relationship of the genotypes of the TP53 codon 72 polymorphism in a large cohort of patients with CLL, to demonstrate the association of codon 72 with the evolution of the disease. Using the IDIPHIM patient database, 558 patients with a diagnosis of CLL were included, with clinical data, immunophenotype studies, FISH, IgHV, and karyotype, at the time of diagnosis and during follow-up. The TP53 codon 72 Arg/Arg, Arg/Pro, and Pro/Pro genotypes were analyzed using RT-PCR and Sanger sequencing techniques. After analyzing the sample of patients, 321 patients with the Arg/Arg genotype, 202 with the Arg/Pro genotype, and 35 with the Pro/Pro genotype were found. In the comparative analysis of the three groups, the patients with the Pro/Pro genotype had a higher number of patients in advanced stages B and C. The latter had a significant association with Binet staging (p = 0.002) compared to the other groups. Likewise, patients with the Pro/Pro genotype had a higher incidence of Richter transformation, whose association was significant (p = 0.013). Also, the patients who were within the Pro/Pro genotype group showed a significant association (p = 0.030) with the Time to the first treatment (TFT), also observing that the group of patients with the Arg/Pro genotype had a more considerable time until your first treatment. 19.7% (110/558) had a second neoplasm, having a significantly higher association with the homozygous groups (Arg/Arg and Pro/Pro) than with the Arg/Pro group, which on the contrary, had fewer second neoplasms (p = 0.016) (see Table 1). Regarding the type of tumors, we found 14.5% of the bladder, 14.5% of the skin, 14.5% of the colon, 13.6% of the prostate, and 12.7% of the lung. No associations were found between Codon 72 and CD38+, ZAP70+, complex karyotype, IgHV, NOTCH-1, del 11q, 12+, p53, del 13q, TP53 mutation. Still, when forming a group between the p53 deletion and TP53 mutation, if significant differences were found (p = 0.023), Pro / Pro group had the highest percentage. The overall survival was 156.32 months (139.92 - 172.72), showing that patients with the Arg/Pro genotype live 40 months more significantly than the other groups (p = 0.028) (see Figure 1). Finally, in the multivariate analysis, age, complex karyotype, 11q deletion, p53 deletion, unmutated IgHV, and Pro/Pro genotype at codon 72 were identified as independent variables associated with an increased risk of death (see Table 2). In conclusion, the Pro/Pro genotype of TP53 Codon 72 has a potential role in the progression and the higher mortality of patients with CLL. Conversely, the Arg / Pro genotype was associated with a lower incidence of second malignancies and higher overall survival. Disclosures No relevant conflicts of interest to declare.

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