Comparison of isolates and antibiotic sensitivity pattern in pediatric and adult cancer patients; is it different.

BACKGROUND: Infection is a common cause of mortality and morbidity in cancer patients. Organisms are becoming resistant to antibiotics; age appears to be one of the factors responsible. We analyzed common organisms and their antibiotic sensitivity pattern in the correlation with age. METHODS: This is a single institutional, retrospective analysis of all culture positive adult and pediatric cancer patients from January 2007 to December 2007. For statistical analysis, Chi‑square test for trend was used and P values were obtained. Of 1251 isolates, 262 were from children <12 years of age and 989 were from adolescents and adults (>12 years of age). Gram‑negative organisms were predominant (64.95) while Gram‑positive constituted 35.09% of isolates. RESULTS: The most common source in all age groups was peripheral‑blood, accounting to 47.8% of all samples. The most common organisms in adults were Pseudomonas aeruginosa (15.3%) while in children it was coagulase negative Staphylococcus aureus (19.8%). Antibiotic sensitivity was different in both groups. In pediatric group higher sensitivity was seen for Cefoparazone‑sulbactum, Cefipime, Amikacin, and Tobramycin. No resistance was found for Linezolid. CONCLUSIONS: The isolates in both children and adults were predominantly Gram‑negative though children had proportionately higher Gram‑positive organisms. High‑dose cytarabine use, cotrimoxazole prophylaxis, and frequent use of central lines in children especially in hematological malignancies could explain this observation. Children harbor less antibiotic resistance than adults; Uncontrolled, cumulative exposure to antibiotics in our community with increasing age, age‑related immune factors and variable bacterial flora in different wards might explain the higher antibiotic resistance in adults. Thus age is an important factor to be considered while deciding empirical antibiotic therapy.

Management of febrile neutropenia in malignancy using the MASCC score and other factors: Feasibility and safety in routine clinical practice.

BACKGROUND: The current standards for empirical broad‑spectrum intravenous antibiotic (AB) treatment, combined with hospitalization, are cautious and safe, but lead to over‑treatment of a substantial group of patients. We need to validate parameters to identify these low‑risk febrile‑neutropenia (FN) patients, who could then be safely treated in an outpatient setting with minimal/no AB treatment. MATERIALS AND METHODS: A retrospective analysis for validation of a risk‑assessment model in FN patients was done on a patient population from January 2007 to December 2008. Inclusion criteria were a histological diagnosis of malignancy, FN secondary to chemotherapy, absolute‑neutrophil‑count of ≤500/μl, axillary temperature of ≥38°C, and age ≥14 years. Other clinical and laboratory parameters were explored for risk stratification during the FN episodes. Receiver‑operating characteristic curves were used to find the threshold value, and Chi‑square analysis was done to find the association between the outcome and the parameters. RESULTS: A total of 178 FN episodes were documented; 22 in solid tumors and 156 in hematolymphoid malignancies. Culture positivity was documented in 59 episodes; peripheral blood was the most common source, with Escherichia coli being the most common organism identified. Risk stratification was done using the Multinational Association of Supportive Care in Cancer (MASCC) risk‑index score. The association between the MASCC score and risk stratification could not be established (P = not significant) at a score of ≤21; however, it was found to be significant at a score of ≤18. The total number of complications was 23 (sepsis 22, mortality 23). Other factors found to be significantly associated with a high risk of complications in the univariate analysis were, mucositis (P = 0.03), maximum temperature ≥103°F (P = 0.01), tachycardia (P < 0.001), tachypnea (P = <0.001), age (P = 0.006), high dose of steroid (P < 0.001), total duration of fever (≥2.5 days (for which sensitivity (S) and specificity (Sp) were 87 and 81%, respectively), serum‑creatinine (≥0.45 mg%, S = 100%, Sp = 97%), serum‑bilirubin (≥0.5 mg/dl, S = 100%. Sp = 90%), requirement of second‑line antibiotics (P = 0.02), intensive‑care (P ≤ 0.001), ventilatory support (P < 0.001), and requirement of packed cell (PC) transfusion (P = 0.02). In the multivariate analysis, mucositis (P = 0.02), HD steroid use (P = 0.026), and PC requirement (0.026) were identified as independent variables. CONCLUSIONS: The MASCC risk‑index score was found to be meaningful at a score of ≤18. Other clinical and laboratory parameters were found to have a strong association with risk stratification in cancer patients during FN episodes.

Alarming prevalence of community-acquired multidrug-resistant organisms colonization in children with cancer and implications for therapy: A prospective study.

BACKGROUND: Infection or colonization with multidrug‑resistant organisms (MDRO) is associated with high mortality and morbidity. Knowledge of MDRO colonization may help in planning empirical antibiotic approach in neutropenic patients, which is known to improve patient outcomes. While routine cultures are positive and may help direct antibiotic therapy in only up to 15% neutropenic patients, surveillance cultures are positive in more than 90% of cancer patients. AIMS: To assess the rate of MDRO carrier status at presentation and rate of conversion to MDRO during the treatment. MATERIALS AND METHODS: Rectal swabs of all the outpatients presenting to pediatric oncology unit were sent within 7 days from date of registration from January 2014 to December 2014. Furthermore, stool cultures/rectal swabs of all patients who got directly admitted to the pediatric ward at presentation were sent within 24 h. Repeat rectal swabs were sent again for patients from this cohort when they got readmitted to the ward at least 15 days after last discharge or when clinically indicated. RESULTS: Baseline surveillance rectal swabs were sent for 618 patients, which included 528 children with hematological malignancies and 90 children with solid tumors. Forty‑five (7.3%) showed no growth. Of the remaining 573, 197 (34.4%) patients were colonized by two organisms and 30 (5.2%) by three organisms. Three hundred and thirty‑four (58.4%) showed extended spectrum beta‑lactamase (ESBL) Enterobacteriaceae, of which 165 (49.5%) were ESBL sensitive to beta‑lactam with beta‑lactamase inhibitors combinations and 169 (50.5%) were resistant to combinations. One hundred and sixteen (20.2%) were carbapenem‑resistant Enterobacteriaceae (CRE) and 65 (11.4%) had vancomycin‑resistant enterococci in baseline cultures. Only 63 (21%) patients were colonized by a sensitive organism in their baseline surveillance cultures. Morbidity (Intensive Care Unit stay) and mortality was higher in patients colonized by MDR organisms. There was a significant correlation between the place of residence and CRE colonization status with the highest rate (60%) of CRE colonization observed in children from East India. The repeat cultures showed the further conversion of sensitive isolates to MDRO in 80% of these children, of which 40% each converted from non‑ESBL and non‑CRE to ESBL and CRE, respectively. CONCLUSION: This is the first study illustrating the alarming high prevalence of community‑acquired MDRO colonization, especially CRE, which has grave implications for therapy for children with cancer potentially compromising delivery of aggressive chemotherapy and affecting outcomes. This incidence further increases during the course of treatment. Knowing the baseline colonization also guides us for the planning of chemotherapy as well as antibiotic approach and infection control strategies. Local antibiotics stewardship including education of the healthcare workers as well as national level interventions to prevent antibiotic misuse in the community is critical to minimize this problem.

Epidemiology of blood stream infections in pediatric patients at a tertiary care cancer centre.

BACKGROUND: Blood stream infections (BSI) are among the most common causes of preventable deaths in children with cancer in a developing country. Knowledge of its etiology as well as antibiotic sensitivity is essential not only for planning antimicrobial policy, but also the larger infection prevention and control measures. AIMS: To describe the etiology and sensitivity of BSI in the pediatric oncology unit at a tertiary cancer center. MATERIALS AND METHODS: All the samples representative of BSI sent from pediatric oncology unit during the period of January to December, 2013 were included in the study, and analyzed for microbiological spectrum with their antibiotic sensitivity. RESULTS: A total of 4198 samples were representative of BSI. The overall cultures positivity rate was 6.97% with higher positivity rate (10.28%) from central lines. Of the positive cultures, 208 (70.9%) were Gram‑negative bacilli (GNB), 71 (24.2%) were Gram‑positive organisms, and 14 (4.7%) were Candida species. Lactose fermenting Enterobacteriaceae i.e., Escherichia coli (28.4%), Klebsiella pneumoniae (22.1%), and Enterobacter (4.8%) accounted for 55.3% of all GNB. Pseudomonas accounted for 53 (25.5%) and Acinetobacter 19 (9.1%) of GNB. Among Gram‑positive isolates, staphylococci were the most frequent (47.8%), followed by Streptococcus pneumoniae 17 (23.9%), beta‑hemolytic streptococci 11 (15.5%), and enterococci 9 (12.68%). Of GNB, 45.7% were pan‑sensitive, 24% extended spectrum beta–lactamase (ESBL) producers, 27% were resistant to carbapenems, and 3.4% resistant to colistin. Pseudomonas was most sensitive, and Klebsiella was least sensitive of GNB. Of the staphylococcal isolates, 41.67% were methicillin-resistant Staphylococcus aureus (MRSA) and 10% of Coagulase Negative Stapylococci (CONS) were methicillin. CONCLUSION: A high degree of ESBL producers and carbapenem‑resistant Enterobacteriaceae is concerning; with emerging resistance to colistin, raising the fear of a return to the preantibiotic era. An urgent intervention including creating awareness and establishment of robust infection control and antibiotic stewardship program is the most important need of the hour.

Sunitinib in metastatic renal cell carcimoma: A single-center experience.

INTRODUCTION: Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine‑kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS: An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: Fifty‑nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose‑modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression‑free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand–foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION: Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow‑up is essential for optimum therapy.

Can combination metronomic therapy overcome chemoresistance in cholangiocarcinoma: A literature review.

Cholangiocarcinoma (CCa) is relatively resistant to chemotherapy as well as radiation therapy, and complete resection is the main curative therapy for these patients. The prognosis for patients with unresectable intrahepatic CCa (iCCa) is extremely poor. A 55‑year‑old woman presented at our hospital with abdominal pain. After evaluation, she was diagnosed to have multifocal iCCa. She did not opt for standard chemotherapy and therefore received oral metronomic therapy with a combination of celecoxib, etoposide, and cyclophosphamide for a total of 30 months. Presently, she is 57 months post diagnosis and 27 months post cessation of all treatment and continues to be in complete radiological remission. In the present report, we review the literature and discuss whether metronomic scheduling of biologic agents and anticancer drugs will be able to overcome chemoresistance and improve the outcome in cholangiocarcinoma. References for the review were identified through searches of Pubmed for the last 10 years as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Metronomic therapy: Chemotherapy revisited.

Cytotoxic antiproliferative chemotherapeutic agents are the mainstay of treatment in cancers. Chemotherapy is usually administered every 2–3 weeks. Along with acute toxicity and long‑term effects of cumulative doses, this strategy potentially allows regrowth of the tumor in the interval period and leads to the emergence of resistant populations of tumor cells. Moreover, even with intense chemotherapy, the outcome is stagnating for most of the tumors. There has been recent interest in the use of chemotherapy in fractionated doses which is far below the maximum tolerated dose. This is called metronomic scheduling of chemotherapy. Here, we review the biology and evidence for metronomic chemotherapy.

Oral metronomic scheduling of anticancer therapy-based treatment compared to existing standard of care in locally advanced oral squamous cell cancers: A matched-pair analysis.

CONTEXT: Head and neck cancers in developing countries present with advanced disease, compounded by poor access to tertiary care centers. AIM: We evaluated oral metronomic scheduling of anticancer therapy (MSAT) in advanced operable oral cancers, in conjunction with standard therapy. SETTINGS AND DESIGN: This was a retrospective matched‑pair analysis carried out in a tertiary referral cancer center. MATERIALS AND METHODS: Advanced operable oral cancer patients having a waiting period for surgery > 3 weeks were administered MSAT. Patients then underwent standard therapy (surgery +/‑ adjuvant radiation/chemoradiation) as warranted by the disease, followed by MSAT maintenance therapy. Outcomes of the MSAT group were compared with stage‑matched controls with similar waiting periods. STATISTICAL ANALYSIS: Survivals were found using the Kaplan‑Meier method and compared between groups using the log rank test. RESULTS: Response was seen in 75% of 32 patients. Two‑year disease‑free survivals (DFS) in MSAT and control groups were 86.5 and 71.6%, respectively. Two‑year DFS in MSAT group who received at least three months of MSAT was 94.6% (P = 0.03). CONCLUSIONS: Oral MSAT is an economical, effective, and safe adjuvant therapy for oral cancers. It has the potential for preventing progression of the disease and improving DFS.

The effect of age on the bacteria isolated and the antibiotic-sensitivity pattern in infections among cancer patients.

Background: Patients with cancer are predisposed to infections. Antimicrobial patterns and antibiotic sensitivity change with increasing age, making choice of empirical therapy more complicated. Materials and Methods: This single-center study aims to try and assess the influence of age on microbiology and antibiotic sensitivity of organisms causing infection in patients with malignant disease. Results : The five most common bacterial pathogens isolated were Pseudomonas sp (245, 26.2%) > Enterocococcus sp (109, 11.66%) > Staphylococcus aureus (107, 11.44%) > Escherichia coli (106, 11.34%) > Klebsiella sp (99, 10.59%). There was no significant change in the distribution of Gram-positive and Gram-negative bacteria with age. However, there was an increase in the occurrence of the Enterobacteriacea group and a decrease in infections caused by nonlactose fermenters with increasing age. The ESBL production increased from 10.52% (12-19 years) to 24.88% (>50 years) as did oxacillin resistance (from 14.3% to 28.1%) among S. aureus isolates. The activity of most antimicrobial agents decreased with increasing age. The decreasing trend of activity was statistically significant for meropenam (73.3-41.2%) against Pseudomonas sp. and for the activity of the aminoglycosides for Acinetobacter sp (61.1-17.4% for amikacin). Conclusions : This suggests that empirical antibiotic therapy needs to be changed on the basis of the age of the patient. It also appears that combination therapy is essential for the empirical treatment of infections in elderly patients with cancer.

Clinico-hematological profile in biphenotypic acute leukemia.

BACKGROUND: We present a clinico-hematological profile and treatment outcome of Biphenotypic Acute Leukemia (BAL). AIM: Study incidence and subtypes of BAL, correlate with age, morphology, and cytogenetic findings and correlate the clinico-hematological data with the treatment response. St Jude's and the EGIL's criteria have been compared for their diagnostic and clinical relevance. MATERIAL AND METHODS: Diagnosis was based on WHO classification, including clinical details, morphology, cytochemistry, immunophenotyping, and molecular genetics. We included those cases, which fulfilled the European Group for the Immunological Characterization of Acute Leukemia's (EGIL's) scoring system criteria for the diagnosis of BAL, as per recommendation of the WHO classification. RESULTS: There were 32 patients diagnosed with BAL, based on EGIL's criteria. Incidence of BAL was 1.2%. B-Myeloid (14 cases) followed by T-Myeloid BAL (13 cases) were the commonest subtypes. Polymorphous population of blasts (16 cases) was commonly associated with T-Myeloid BAL (10 cases). BCR ABL fusion positivity was a common cytogenetic abnormality (seven cases). Fifteen patients received chemotherapy; eight achieved complete remission (CR) at the end of the induction period. CONCLUSIONS: Pediatric BAL and T-B lymphoid BAL have a better prognosis. A comprehensive panel of reagents is required, including cytoplasmic markers; to diagnose BAL. St Jude's criteria is a simple, easy, and cost-effective method to diagnose BAL. The outcome-related prognostic factors include age, HLA-DR, CD34 negativity, and subtype of BAL. BCR-ABL expression is an important prognostic factor, as these cases will be labeled as Chronic myeloid leukemia (CML) in blast crisis with biphenotypic expression and treated accordingly.

Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we present the initial data of the first seven patients treated at our institution. MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks. RESULTS: After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died. CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.

Desmoplastic small round cell tumor: extra abdominal and abdominal presentations and the results of treatment.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm of adolescent males. Current multimodality treatment prolongs life and rarely achieves cure. AIM: To review the presenting features, histopathology and outcome of 18 patients with DSRCT treated at a single institution. SETTING AND DESIGN: This is a retrospective observational study of patients with DSRCT who presented at the Tata Memorial Hospital between January 1994 to January 2005. MATERIALS AND METHODS: Eighteen patients of DSRCT seen during this period were evaluated for their clinical presentation, response to chemotherapy and other multimodality treatment and overall survival. The cohort of 18 patients included 11 males (61%) and 7 females (39%) with a mean age of 16 years (Range 1(1/2)--30 years). Majority (83%) presented with abdomino-pelvic disease. The others, involving chest wall and extremities. There were 6 patients (33%) with metastatic disease at presentation. RESULTS: The treatment primarily included a multimodality approach using a combination of multiagent chemotherapy with adjuvant surgery and radiotherapy as applicable. A response rate of 39% (CR-1, PR-6), with chemotherapy was observed. The overall response rate after multimodality treatment was 39% (CR-5, PR-2). The overall survival was poor except in patients who had complete excision of the tumor. Conclusion:0 Abdomino-pelvic site was the commonest presentation, the disease can occur at other non-serosal surfaces also. Despite aggressive treatment the outcome was poor. However, complete surgical excision seems to provide a better survival.

Non-Hodgkin's lymphoma of prostate: a rare site of primary extranodal presentation (a report of two cases).

We report two cases of primary extranodal lymphoma of the prostate, an unusual site for extranodal presentation. The clinical presentation and treatment is discussed.

Low dose, oral lorazepam: a safe and effective adjuvant to antiemetic therapy.

Twenty-five patients with acute nonlymphoblastic leukemia undergoing 41 cycles of chemotherapy with daunorubicin/cytosine arabinoside (ara-C) or with etoposide/ara-C received metoclopramide (MCP; 0.5 mg/kg 6 hourly i.v.) or MCP (same dose) plus oral lorazepam (1 mg/d) during and 24 hours following the chemotherapy as antiemetic medication. Control of vomiting was achieved is 55% (complete 5%, partial 50%) of the patients receiving MCP alone and in 100 percent (complete 76.1%; partial 23.8%) of those receiving MCP plus lorazepam (p less than 0.001). Eighteen of the 21 patients (85.7%) receiving MCP plus lorazepam opted for the same antiemetic regimen as compared to six of the 20 (30%) receiving MCP alone (p less than 0.01). One patient in each group developed mild sedation during the treatment. It is concluded that oral lorazepam is an effective and safe adjuvant to MCP for the control of vomiting during cancer chemotherapy.

Cytotoxic therapy. Role of durable venous access.

Aggressive chemotherapy regimens and supportive measures in haemato-oncology patients demand reliable venous access. Experience with this method in India has been limited. During a period of six months, we have used 42 subclavian indwelling catheters and 31 cubital Cavafix long lines. The mean age of patients in the two groups was 32 years and 7 years respectively. Subclavian catheters had a median duration of catheter placement of 46 days (range 4-145) and total 1494 catheter days, while cubital longlines yielded a median duration of insertion of 14 days (range 4-27) and total 508 catheter days. Catheter related complications were infection in 25% of patients, thrombophlebitis in 22%, blockade in 12% and misplacement in 17% in both groups taken together. The patients and families were extremely satisfied with the devices. Our experience supports further use of durable venous access in cancer patients. Implanted central venous catheters should be preferred whenever feasible.

Primary pulmonary non-Hodgkin's lymphoma: a report of four cases.

Four cases of primary non-Hodgkin's lymphoma of the lung are described. Two cases had low and two intermediate grade lymphoma at the time of diagnosis. The patient who had disease for long duration and received pulmonary radiotherapy developed intractable chest infection and died six months after diagnosis; the three patients having short history of disease and treated with surgery and/or chemotherapy have been doing well for 4 to 77 months after the diagnosis. It is concluded that diagnosis of primary pulmonary lymphoma should be suspected in patients with nodular or interstitial lung disease and bronchoalveolar lavage with aspiration cytology should be done to make an early diagnosis.

Use of central venous catheters for prolonged venous access in cancer chemotherapy.

A preliminary experience in the use of central venous catheters, including Hickman (15), subclavian jugular (Desseret) (50) and Secalon Hydrocath (3), in cancer chemotherapy is presented. There were no technical complications and no mortality attributable to catheterisation. Infections formed the major complication in Hickman (30%) and subclavian jugular (Desseret) (36%) catheters, while the use of Secalon Hydrocath was event-free. The commonest organism isolated was P aeruginosa (60%), followed by staphylococci (30%). Prolonged venous access was achieved with minimum morbidity. It is concluded that central venous catheters are safe and convenient both for the patient and the treating team, and should be used in all patients undergoing protracted chemotherapy and supportive care.

Acute non-lymphoblastic leukemia in children: prognostic factors and results of chemotherapy.

Twenty-nine children (age range 1-14, median 8 years) with acute non-lymphoblastic leukemia (ANLL) were induced in remission with daunorubicin and cytosine arabinoside. Twenty-three (79.3%) patients achieved complete remission (CR) and were administered two cycles of the same drugs as consolidation therapy; no maintenance treatment was given. Three (10.3%) patients died during induction; 3 (10.3%) patients were resistant to therapy. Multivariate analysis showed that female sex, TLC less than 50 X 10(9)/L, absence of in ection, albumin greater than 3.5 g/dl and high myeloperoxidase activity had a favourable influence on achievement of CR. TLC less than 50 X 10(9)/L and albumin greater than 3.5 g/dl also had a favourable prognostic value. Eight patients are alive between 13 and 32 months with overall survival at 2 years being 27.5%; four patients are free of disease with projected DFS at 2 years being 13.7%. The present data indicates the need for newer approaches to improve the long term survival in childhood ANLL.