The future of cancer treatment: combining radiotherapy with immunotherapy.

Radiotherapy (RT) and immunotherapy (IT) are the powerful tools for cancer treatment which act through the stimulation of immune response, and evidence suggest that combinatorial actions of these therapies may augment each other's beneficial effect through complex synergistic mechanisms. These molecular strategies are designed to target rapidly dividing cancer cells by either directly or indirectly inducing DNA damage. However, when cells detect DNA damage, they activate a range of signalling pathways known as the DNA damage response (DDR) to repair. Strategies are being developed to interfere with the DDR pathways in cancer cells to ensure their damage-induced degeneration. The stability of a cell's genetic material is largely dependent on the efficacy of DNA repair and therefore, an in-depth understanding of DNA damages and repair mechanism(s) in cancer cells is important to develop a promising therapeutic strategies for ensuring the efficacy of damage-induced tumor cell death. In recent years, a wide range of small molecule drugs have been developed which are currently being employed to combat the DNA repair deficiencies associated with tumor cells. Sequential or concurrent use of these two modalities significantly enhances the anti-tumor response, however with a concurrent probability of increased incidence of symptomatic adverse effects. With advent of newer IT agents, and administration of higher doses of radiation per fraction, such effects are more difficult to predict owing to the paucity of randomized trial data. It is well established that anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), anti- Programmed cell death protein 1(PD-1), anti-Programmed cell death one ligand 1 (PD-L1) can be safely administered with RT and many studies have demonstrated survival benefit with such combination for patients with metastatic malignancy. However, the biology of radioimmunotherapy (RT/IT) is still an open area where research need to be focused to determine optimum dosage specially the interaction of the RT/IT pathways to determine optimum dosing schedule. In the current article we have summarised the possible intracellular immunological events that might be triggered when RT and IT modalities are combined with the DDR antagonists and highlighted present clinical practices, outcome, and toxicity profile of this novel treatment strategy.

Bioavailable Vitamin D Levels in Children With First Episode Nephrotic Syndrome: A Longitudinal Study.

OBJECTIVE: To estimate the levels of serum bioavailable vitamin D in children presenting with first episode nephrotic syndrome (FENS) at diagnosis and after 4 weeks of standard steroid therapy while the child is in remission, and compare the same with age-sex matched healthy controls. METHODS: We included children aged 1 month to 12 years presenting as FENS and estimated the serum calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D (25(OH)D), parathormone, serum and urine Vitamin D binding protein (VDBP) at diagnosis and after 4 weeks of standard steroid therapy while the child is in remission. We also included age-sex matched healthy controls for comparison. Bioavailable and free 25(OH)D were estimated at enrolment and at 4 weeks of therapy. RESULTS: The mean(SD) 25(OH)D level (ng/mL) in children with FENS was 11.3 (6.1) at diagnosis and 13.6 (6.2) at 4 weeks follow-up, while the observed value in healthy controls was 16 (7) ng/mL. The median (IQR) serum VDBP level in FENS at enrolment was 223.0 (144, 305.5) µg/mL. There was significant correlation of serum VDBP with serum albumin levels (P = 0.04). At 4 weeks (remission), the median (IQR) VDBP levels increased to 554.5 (383, 644.75) µg/mL (P < 0.001). The median (IQR) free 25(OH)D levels (pg/mL) in children with FENS was 1.07 (0.8, 1.6) at enrolment and 0.53 (0.37, 0.86) at 4 weeks follow-up. The median (IQR) bioavailable vitamin D in FENS during proteinuria was 0.58 (0.4, 0.83) ng/ml, much lower as compared to controls 0.97(0.85, 1.08) ng/ml (P < 0.001). On follow-up at 4 weeks of remission the median (IQR) bioavailable vitamin D levels increased to 0.87 (0.59, 1.42) ng/ml (P = 0.015). There was a very strong positive correlation between free vitamin D and bioavailable vitamin D (r = 0.9, P < 0.001); a strong negative correlation between serum VDBP and bioavailable vitamin D (r = - 0.69, P < 0.001). There was a positive correlation between 25-hroxy vitamin D and bioavailable vitamin D (r = 0.63, P < 0.001). A positive correlation was seen between urine UP/UC and urine VDBP (r = 0.51, P = 0.004). Serum VDBP and serum albumin showed statistically significant positive correlation (r = 0.37, P < 0.05). CONCLUSION: Children with FENS are deficient in vitamin D. The free and bioavailable vitamin D levels are reduced in children with FENS during the proteinuric phase. Further studies to assess the association between bioavailable vitamin D and 25(OH)D with bone mineral density are needed in children with nephrotic syndrome to validate the utility of bioavailable vitamin D in clinical practice.

Efficacy of 15% trichloroacetic acid peel versus 35% glycolic acid peel in acanthosis Nigricans: A randomized open-label study.

Introduction: Acanthosis Nigricans (AN) is an acquired disorder of keratinization. It presents as hyperpigmentation, velvety texture of skin that can involve any part of the body including the face. Different topical, systemic therapies, or physical therapies including laser have been explored. However, there are not many randomized controlled studies for the majority of therapy alternatives besides lifestyle modifications and weight reduction. Objectives: The aim of this study was to compare the effectiveness of 15% trichloroacetic acid (TCA) and 35% glycolic acid (GA) peel for AN. Materials and Methods: Forty participants were included and randomized into two groups. In groups A and B, peeling with 15% TCA and 35% GA was done, respectively. The effectiveness of each peel was assessed using changes in the Acanthosis Nigricans Area and Severity Index Score (ANASI) and Physician Assessment Score. Statistical analysis included Wilcoxon-Mann-Whitney test, Friedman test, and generalized estimating equations. Results: The overall change in ANASI over time was compared in the two groups using the generalized estimating equations method. A significant difference was observed in the trend of ANASI over time between the two groups (P < 0.001). TCA peel group showed more change in ANASI as compared with GA peel group. Conclusion: In our research, 15% TCA has a better efficacy when compared with 35% GA peel after three sessions of chemical peeling. We therefore recommend the use of 15% TCA peel in AN as a safe and effective treatment option. However, more comprehensive randomized control studies are required for supporting data.

Serum Inflammatory Markers in Children with Severe Acute Malnutrition with Systemic Infections: A Case-Control Study.

Severe acute malnutrition (SAM) is a major contributor to under-five mortality in developing countries such as India, where SAM children are susceptible to infections. However, there is inconsistent literature on the derangement of immune mechanisms and subsequent infection-related mounting of inflammatory responses in SAM cases compared to nutritionally-normal controls with infections. To address this, authors conducted a case-control study comparing serum inflammatory markers in 60 SAM children with systemic infections to nutritionally-normal children with infection. Cases had a lower mean serum C-reactive protein (CRP) on admission compared to controls (p-value <0.001), which continued during the follow-up (p-value <0.001). Cases also had a lower mean serum interleukin-6 (IL-6) on admission (p-value = 0.04). Baseline CRP, procalcitonin, and follow-up procalcitonin were positively correlated with antibiotic therapy duration (p-value = 0.018, 0.025, and 0.007, respectively). This study suggests that SAM children had some ability to mount an inflammatory response during a systemic infection, but it was weaker compared to nutritionally normal children with a systemic infection.

Biochemical and hormonal abnormalities in adult female acne.

BACKGROUND: Prevalence of adult patients with acne is increasing and women comprise majority of the cases. There is lack of data on biochemical and hormonal abnormalities in adult female acne (AFA). AIMS: To evaluate biochemical and hormonal parameters in 60 patients of AFA. METHODS: A cross-sectional observational study conducted from November 2018 to March 2020 in Dermatology outpatient department of a tertiary care hospital in North India. Adult females (age > 25 years) with a clinical diagnosis of acne were included in the study. RESULTS: 60 cases of AFA were included. The age ranged between 26-41 years with mean age at presentation being 29.45 years. 53.3% patients had persistent acne while 46.7% had late-onset acne. 50% patients had history of premenstrual flare-up of their acne. Raised FBG was found in 25% patients. 10% had raised serum insulin levels. HOMA-IR index was deranged in 55% patients. At least one lipid alteration was reported in 91.6% of patients. In hormonal parameters, raised TT was present in 6.7%, LH in 3.3%, FSH in 18.3%, prolactin in 3.3%, and TSH in 15%. No association was found between acne severity and biochemical and hormonal parameters. CONCLUSIONS: Our study highlighted the importance of measuring lipid profile in AFA and calculating HOMA-IR index for measuring insulin resistance rather than simply measuring serum insulin levels. In our study, additional parameter deranged in significant number of patients was FBG. Hence, we recommend routine screening of lipid profile, FBG and calculation of HOMA-IR index in AFA.

Association between the physical activity and metabolic syndrome in residents of a foot-hill area in India.

BACKGROUND AND AIMS: Physical inactivity, has been linked to development of metabolic syndrome, which increases the risk of developing cardiovascular disease. Aim of the study was to assess the level of physical activity and it's association with prevalence of metabolic syndrome and oxidative stress in a semiurban foothill population of India. METHODS: Participants (n = 288), >18 years of age were enrolled. Their demographics and clinical details were recorded. Fasting plasma glucose, triglycerides, cholesterol and erythrocyte glutathione peroxidase activity were measured. Physical activity was estimated using Global Physical Activity Questionnaire and converted into metabolic equivalent in minutes per week. RESULTS: 37.5% of study population was found to be physically active, with more males (43.3%) being active than females (23.3%). Inactivity was associated with higher triglycerides levels in males and with higher hip circumference, diastolic blood pressure, triglycerides and fasting plasma glucose in females. No significant difference was found in the oxidative stress, indicated by decreased glutathione peroxidase activity, between active and inactive persons or persons with normal and increased body mass index. CONCLUSIONS: There is a high prevalence of physical inactivity in this region of India, with prevalence of physical inactivity higher is females as compared to males. No significant co-relation was found between the levels of activity and components of metabolic syndrome and oxidative stress in the study population.

Cerebral dominance in an unusual case of Landau-Kleffner syndrome.

Landau-Kleffner syndrome (LKS) is described by the International Classification of Epileptic Syndromes since 1985 as a constellation of clinical and electrographic signs, including acquired aphasia, regression of language milestones and seizures, along with sleep-activated paroxysms on electroencephalogram which can progress to electrographic status epilepticus of sleep. In this case, a 7-year-old boy presented with an atypical history of new-onset aphasia and regression of language milestones with rare seizures. However, there was an electrographic mismatch in the form of right-sided epileptiform activity and continuous spike and wave of sleep pattern. Detailed speech analysis and perusal of the history revealed a possibly ambidextrous child with right hemispheric language dominance, and he was diagnosed with LKS and treated. This report illustrates the many pitfalls in the diagnosis and treatment of this rare epileptic syndrome.

Nipah Virus Disease: Recent Perspective and One Health Approach.

Background: Nipah virus (NiV) first emerged in 1998 in Malaysia, causing an outbreak of respiratory illness and encephalitis in pigs. Pig-to-human transmission of NiV associated with severe febrile encephalitis was described, and it was thought to occur through close contact with infected animals. The first outbreak was reported in India in Siliguri, West Bengal in 2001 followed by Nadia, West Bengal and adjoining areas of Bangladesh in 2007, where an intermediate animal host was not identified, suggesting bat-to-human and human-to-human transmissions. Although it is extremely difficult to document the spillover event and ascertain crossing of trans-natural boundaries by bats and bringing new viruses in an unexposed population, efforts for source identification are important to understand the epidemiology of disease. As the disease transcends beyond one species and has shown to infect humans, it therefore requires the 'One Health approach' in which multiple sectors coordinate and work together to achieve better public health outcomes. Objective: We summarize the re-emergence and response of the Nipah virus outbreaks (NiVD) in Kerala, India, about 1800 kms away, a decade later in 2018 and 2019. The paper recapitulates involvement of various stakeholders from the Ministry of Health and Family Welfare, Directorate of Health Research, Indian Council of Agricultural Research, State Health Department, State Animal Husbandry, District Administration, and multidisciplinary response mechanism during the NiVD outbreaks of 2018 and 2019. Methods: Information was collected from the Press Information Bureau (PIB), media/weekly alerts from the Integrated Disease Surveillance Programme (IDSP), news articles from print and electronic media, newsletters, advisories from the National Centre for Disease Control (NCDC), Disease Outbreak News (DON), World Health Organization (WHO), and published papers from various stakeholders. Findings & Conclusion: The evidence of NiV in humans and bats, with samples collected from the outbreak sites, was laboratory confirmed. The multidisciplinary response mechanisms during the 2018 outbreak helped in further understanding the importance of the One Health approach for systemic and streamlined response utilizing existing surveillance systems. This was of utmost help in the subsequent outbreak of the disease that occurred during 2019, wherein there was no documented spread of disease from the index case and no mortality was observed. This success reiterates the need for institutionalizing the involvement and cooperation of various departments and organizations during public health emergencies, especially of Zoonotic diseases, using the One Health approach.

Appropriateness of Lower Waist Circumference Cutoffs for Predicting Derangement in Metabolic Parameters Among Asian Children and Adolescents: A Pilot Study.

Waist circumference (WC) >90th percentile cut-off effectively screens children for metabolic syndrome, as some specific metabolic derangements (high fasting serum levels of insulin and triglycerides) may be better associated with lower (70th percentile) waist circumference cut off. We evaluated a subset of children and adolescents found obese or overweight following the anthropometric screening in a school-based survey. Metabolic parameters (fasting insulin levels, fasting blood sugar and fasting lipid profile and blood pressure) were compared among 3 groups of obese or overweight children divided on the basis of WC percentiles (>90th, 70th-90th and <70th). 78 children (aged 11-18 years, 45 boys) were evaluated. The proportion of participants with high triglycerides and fasting insulin among those with WC<70th (28.6%, 19%) was significantly lower than that in the group with WC >90th (76.9%, 53.8%) as well as in group with WC 70th-90th percentile (38.7%, 41.9%).

Wilson's Disease Masquerading as Juvenile Idiopathic Arthritis in an Adolescent.

Wilson's disease (WD) is a rare autosomal-recessive inborn error of copper metabolism characterized by the toxic accumulation of copper in liver, brain, cornea, and other tissues. It has a variable clinical presentation. Musculoskeletal presentations are very unusual. We report a 17-year-old male who presented to us with juvenile idiopathic arthritis (JIA), which later proved to be a case of WD.

Study of serum vitamin D levels in men with premature androgenetic alopecia.

BACKGROUND: Vitamin D deficiency had been associated with various hair loss disorders, such as telogen effluvium, alopecia areata, and female pattern hair loss. However, previous studies have not found a correlation between serum vitamin D levels and the severity of androgenetic alopecia. METHODS: A case-control study was conducted for a period of one year in a public tertiary care hospital. Fifty males clinically diagnosed with androgenetic alopecia and 50 age-matched healthy controls were recruited. Serum vitamin D levels in both cases and controls were measured by radioimmunoassay technique, and the results were compared. RESULTS: A total of 50 cases and 50 controls were recruited and analyzed. The mean age of the cases was 23 years and that of controls was 24.2 years. The mean levels of serum vitamin D significantly decreased in cases, compared to controls (20.10 vs. 29.34 ng/mL; P ≤ 0.001). Eighty-six percent of the cases had deficiency of vitamin D (<30 nmol/L), while 14% had insufficient vitamin D levels (31-50 nmol/L). There was a positive correlation between vitamin D deficiency and severity of androgenetic alopecia (AGA), which was statistically significant (P ≤ 0.5). However, there was no correlation between the duration of sun exposure and serum vitamin D levels (2.36 ± 1.2 in cases and 3.23 ± 1.6 in controls, P value = 0.98). CONCLUSION: Our study showed a significant correlation between vitamin D deficiency and the severity of androgenetic alopecia. This suggests that vitamin D may play a role in the premature onset of androgenetic alopecia. However, further studies on a larger population and the effect of vitamin D supplementation on the progression of androgenetic alopecia are required to validate the above findings.

Single point insulin sensitivity estimator as an index for insulin sensitivity for metabolic syndrome: A study in North Indian population.

BACKGROUND: Various indices for estimating insulin sensitivity, based on glucose tolerance test and fasting insulin levels, have been devised. However, they are laborious, time-consuming, and costly. Recently, a new index, single point insulin sensitivity estimator (SPISE) based on TG, high-density lipoproteins (HDL), and body mass index (BMI) was proposed in the European population and was found comparable to gold standard test. Decreased insulin sensitivity is a hallmark of metabolic syndrome (MetS). Hence, the current study was planned to determine the optimal cutoff of SPISE with high sensitivity and specificity in MetS patients of the North Indian population. MATERIALS AND METHODS: A community-based cross-sectional study including 229 MetS cases and 248 controls was conducted. MetS was defined according to the South Asian Modified National Cholesterol Education Program criteria. SPISE index was calculated for cases and controls using the formula devised by Paulmichl et al.: SPISE = 600 × HDL-C0.185/(TG0.2 × BMI1.338). Receiver operating characteristic (ROC) curve was plotted for determining optimal cutoff for SPISE in MetS. RESULTS: SPISE was significantly lower in MetS patients (5.35 ± 1.35) than that for controls (7.45 ± 2) with P < 0.05 (confidence interval [CI]: 1.79-2.41). ROC curve showed area under the curve = 0.83 for SPISE (P < 0.05, CI: 0.79-0.86), showing SPISE to have good predictive ability to discriminate MetS cases from controls. The cutoff value of SPISE index for predicting insulin sensitivity in MetS was found out to be 5.82 with sensitivity and specificity of 73% and 80%, respectively. This cutoff is lower than the European population (6.61), indicating higher insulin resistance (IR) in the study population. CONCLUSION: SPISE could be a useful potential low-cost indicator with high sensitivity and specificity for predicting IR in MetS.

Study of metabolic syndrome and its risk components in patients attending tertiary care center of uttarakhand.

Metabolic syndrome is a complex of metabolic factors which includes central obesity, insulin-resistance, dyslipidemia and hypertension. Metabolic syndrome is associated with increased risk of cardiovascular disease. This study aimed to know the rate of metabolic syndrome in outpatients presenting to medicine department of our hospital and their profile. The metabolic syndrome was diagnosed using International Diabetes Federation criteria. The parameters analyzed included age, sex, blood pressure, BMI, fasting plasma glucose, HDL and triglycerides. The rate of metabolic syndrome was 21.1 % in our study. The younger population was most susceptible to metabolic derangements. Further, females were found to be affected more than males. The extremely significant parameters were deranged fasting plasma glucose, HDL, triglycerides while hypertension was found to be insignificant. Being overweight maybe a strong predictor for presence of metabolic syndrome in our region of study, and all overweight persons should be assessed and appropriately treated to prevent future cardiovascular events.

Tuberculosis and non-diabetic hyperglycemia: a challenge to public health management.

Diabetes and tuberculosis comorbidity is an emerging challenge for public health management. But the diagnostic criteria for diabetes is based on microvascular complications of diabetes and does not reflect the level of hyperglycemia which affects infectivity of Mycobacterium tuberculosis. Therefore the study protocols focussing on these comorbidities need to be reviewed.

Concomitant detection of biofilm and metallo-beta-lactamases production in gram-negative bacilli.

UNLABELLED: Carbapenems are mainstay of treating serious multidrug resistant gram-negative biofilm-based infections. However, recent emergence of metallo-beta-lactamases (MbL) producing gram-negative bacilli in different parts of world may be related to gain of virulence factors associated with biofilm production. OBJECTIVES: To explore the association of MbL and biofilm production in various gram-negative bacilli. MATERIALS AND METHODS: In this study, 110 non-repetitive ceftazidime resistant gram-negative bacilli were evaluated for biofilm and MßL production. Biofilm forming ability of isolates obtained from various specimens was tested by the tube method. Disks of ceftazidime (30 µg) and ceftazidime with ethylenediaminetetraacetic acid (30 µg + 750 µg, prepared in house) for MßL detection were used. Chi-square test was used to study the association between biofilm and MßL production. P value <0.05 was considered significant. RESULTS: 88 (80%) bacilli had shown biofilm producing ability. The association of biofilm and MßL was significant in cases of non-fermenters as compared to enterobacteriaceae members. CONCLUSION: The particular combination of virulence factors (biofilm and MßL) in bacteria may be a species specific effect which needs to be investigated at molecular level in detail. This may help in designing newer therapies based on interference with biofilm formation and thus countering clinical episodes of antibiotic resistance.

Cerebral venous thrombosis in ulcerative colitis.

Ulcerative colitis has been reported to show hyper coagulation leading to peripheral and rarely central thrombosis. A 35-year-old female was admitted with chief complaints of increased frequency of bloody diarrhea, abdominal pain, and weight loss for 2 months. The patient was diagnosed to have ulcerative colitis after sigmoidoscopy and biopsy and she was started on treatment. Two days later, the patient developed headache and seizures. Magnetic resonance imaging of brain showed cerebral venous thrombosis with venous infarcts. A high index of clinical suspicion is needed to diagnose this uncommon condition so that appropriate treatment can be initiated.

Bacteriological and resistance profile in isolates from diabetic patients.

BACKGROUND: Diabetes mellitus has become a global epidemic illness and poses a threat for development of resistant bacterial infections. AIM: This study was aimed to know the bacteriological and resistance profile of isolates obtained from diabetic patients. MATERIALS AND METHODS: The bacterial isolates obtained from various samples of diabetic patients admitted in medicine department in 6-month period were identified and tested for antibiotic susceptibility. The extended spectrum beta-lactamases (ESßL), AmpC, and metallo-beta-lactamases (MßL) enzymes were detected in gram-negative bacilli. Methicillin, macrolide-lincosamide-streptogramin (MLS), and linezolid resistance in Staphylococcus spp. were detected. High-level aminoglycoside resistance (HLAR) in Enterococcus spp. was also tested. RESULTS: In all, 38 of 125 diabetic patients (30.4%) had bacterial infection, 18 patients had wound infections, 18 had urinary tract infections (UTIs), and 2 had respiratory tract infections. Escherichia coli among gram-negative bacteria and Staphylococcus aureus among gram-positive bacteria were the predominant pathogens. 32.5% gram-negative bacilli were AmpC producers, 37.5% were MßL producers, and 40% were ESßL producers. Methicillin and MLS resistance was found in 50% and 33.3% isolates of Staphylococcus spp., respectively. HLAR resistance was alarming in Enterococcus spp. Polymyxin among gram-negative bacteria and vancomycin for gram-positive bacteria were the last resort with highest susceptibility rates to treat infections among diabetic patients. CONCLUSION: Resistant bacterial infections in diabetic patients are common. The presence of various resistance mechanisms in isolates of our study shows that therapeutic failure can occur if empirical prescription is unsubstantiated.

Primary pulmonary sporotrichosis in a sub-Himalayan patient.

Primary pulmonary sporotrichosis, a rare fungal disease was found in chronic alcoholic farmer from the sub-Himalayan region, an endemic mycoses area. Primary pulmonary sporotrichosis is a hidden entity, at times mimicking tuberculosis, and often under or lately diagnosed due to lack of awareness. We should consider the possibility of pulmonary sporotrichosis in patients with chronic cough and cavitary parenchymal disease, particularly in chronic alcoholics, gardeners, and forest workers. Sputum culture for fungus as a part of diagnostic studies is needed especially in endemic mycoses areas for early detection and management of such fungal diseases.

Evaluation of TNF-α and IL-6 Levels in Obese and Non-obese Diabetics: Pre- and Postinsulin Effects.

BACKGROUND: Type 2 diabetes (T2DM) mellitus is a serious implication of obesity. The effect of insulin therapy on levels of inflammatory markers among obese and non-obese diabetics has been inadequately studied. AIM: The study aimed to analyze the preinsulin and postinsulin levels of tumor necrosis factor α (TNF-α) and IL-6 in nonobese and obese T2DM patients. MATERIALS AND METHODS: We assessed TNF-α and IL-6 levels in healthy controls (n=10) and diabetic patients (obese and nonobese; n=20 each) and analyzed the postinsulin effect on TNF-α and IL-6 levels after 24 and 48 weeks. TNF-α and IL-6 levels were also correlated with fasting plasma glucose of obese and nonobese diabetic patients after insulin therapy. RESULTS: There is augmentation of TNF-α and IL-6 levels in diabetic patients and augmentation is more in obese than in nonobese diabetics. The obese group showed a significant decrease (P value<0.05) after 24 weeks of insulin therapy and an extremely significant decrease (P<0.001) in TNF-α and IL-6 levels after 48 weeks of therapy. The nonobese group showed an extremely significant decrease (P<0.001) in TNF-α and IL-6levels after 24 and 48 weeks both. CONCLUSION: There is augmented inflammation in diabetes and it is more in obese diabetics. Insulin therapy tends to counter this inflammation, but the response is delayed in obese diabetics.

A study on device-related infections with special reference to biofilm production and antibiotic resistance.

BACKGROUND: Indwelling medical devices (IMDs) in critical patients are vulnerable to colonization by biofilm producing bacteria. Complex characteristics of bacterial biofilms promote antibiotic resistance, leading to the emergence of resistant device-related infections (DRI), which pose new challenges in their management. MATERIALS AND METHODS: The study was done on 135 hospitalized (Intensive care units) pediatric patients with IMDs (intravascular catheter, urinary catheter, and endotracheal tube) to determine the device-specific infection rates. Biofilm formations were demonstrated by the tube method and by scanning electron microscopy (SEM). Bacteria in biofilms were identified by the standard conventional methods and tested for antibiotic resistance. We also detected the presence of extended spectrum ß-lactamases (ESßLs), particularly, bla(CTX-M,) in gram-negative isolates. RESULTS: The rates of biofilm-based catheter-related blood stream infections (CRBSI), catheter-associated urinary tract infections (CAUTI), and Ventilator Associated Pneumonia (VAP), in our study, were 10.4, 26.6, and 20%. Biofilm formation by the tube method correlated well with the SEM findings. A majority of infections were caused by Klebsiella pneumoniae followed by Staphylococcal biofilms. A high percentage (85.7%, 95% confidence interval 64.5 to 95.8%) of biofilm producing bacterial isolates, causing infection, were multidrug resistant. Many biofilm producing gram-negative isolates were ESßLs producers, and a majority particularly harbored bla(CTX-M,) among the ESßLs genotypes. CONCLUSION: The incidence of resistant device-related infections, predominantly caused by biofilm producing bacteria, is rising. The tube method is an effective screening method to test biofilm production, where sophisticated microscopy facilities are not available. The varying resistance pattern of organisms isolated in our setup, emphasizes the importance of studying the pattern of infection in every setting and providing antibiotic guidelines in the management of such infections.