Does ciprofloxacin prophylaxis during chemotherapy induce intestinal microflora resistance to ceftazidime in children with cancer?

To determine the susceptibility and minimal inhibitory concentrations (MIC) of ceftazidime, the commonly used empirical antibiotic in patients with febrile neutropenia, in Escherichia coli and Klebsiella pneumoniae isolated from the intestinal microflora of pediatric patients with cancer, who received ciprofloxacin prophylaxis during chemotherapy, children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20 mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before (R0) and at 1 (R1), 2 (R2), and 3 (R3) weeks during the intervention. The antimicrobial susceptibilities and MICs of ceftazidime and ciprofloxacin were determined via the E test. Of the total 87 patients enrolled, 44 received ciprofloxacin and 43 placebo. A total of 350 isolates were obtained, 62, 49, 46 and 22 from the ciprofloxacin group and 68, 54, 38 and 11 from the placebo group at R0, R1, R2 and R3, respectively. The percentages of ceftazidime susceptibility did not show significantly greater decreases from R0 to R1-R3 in the ciprofloxacin group compared to the placebo group. The MIC50s of ceftazidime showed significantly greater increases after ciprofloxacin prophylaxis during R1-R3 compared to R0 in the intervention group compared to the placebo group (R0, 0.12 vs. 0.12; R1, 0.19 vs. 0.12; R2, 0.19 vs. 0.12 and R3, 0.38 vs. 0.09 µg/mL, respectively). Due to the increasing MIC50 of ceftazidime over time after ciprofloxacin prophylaxis, the use of ceftazidime in patients who have previously had ciprofloxacin prophylaxis needs to be closely monitored.

Is zinc concentration in toxic phase plasma related to dengue severity and level of transaminases?

OBJECTIVE: To determine the relationship between plasma zinc values and the severity of dengue viral infection (DVI) and DVI-caused hepatitis. METHODS: A prospective cohort study was conducted during 2008-2010 in hospitalized children aged <15 years confirmed with DVI. Complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and zinc values (mcg/dL) were determined twice: first during the toxic phase (Zn1) and secondly two weeks after recovery (Zn2). RESULTS: 39 patients were enrolled with a mean age of 9.7 ± 3.7 years, and 15/39 diagnosed with dengue shock syndrome (DSS). Zn1 values were lower than Zn2 values [median (IQR): 46.0 (37.0, 58.0) vs 65.0 (58.0, 81.0) mcg/dL, respectively, p <0.01]. Zn1 but not Zn2 values had a negative correlation with AST and ALT (rs = -0.33, p = 0.04 and rs = -0.31, p = 0.05, respectively). Patients with DSS had lower Zn1 but not Zn2 values compared with non-DSS patients [median (IQR) Zn1, 38.0 (30.0, 48.0) vs 52.5 (41.2, 58.7), p = 0.02; Zn2, 61.0 (56.0, 88.0) vs 65.0 (59.5, 77.5), respectively, p = 0.76]. Zn1 values showed a decreasing trend across increasing dengue severity groups (p = 0.02). Age <5 years and DVI-associated diarrhea were associated with low Zn1. CONCLUSION: Children who had a higher grade of dengue disease severity and liver cell injury had lower Zn1 values. Low Zn1 values were probably caused by loss from diarrhea and from zinc translocating to liver cells.

In vitro activity of colistin against multidrug-resistant Pseudomonas aeruginosa isolates from patients in Songklanagarind Hospital, Thailand.

Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection creates problems for therapy. Previous studies have found MDR-PA is susceptible to colistin. We studied the in vitro susceptibility of MDR-PA to colistin and determined the minimum inhibitory concentration (MIC). One hundred MDR-PA isolates were obtained from patients at Songklanagarind Hospital, in southern Thailand, during January 2008-March 2011. Antimicrobial susceptibilities to amikacin (AK), ceftazidime (CAZ), ciprofloxacin (CIP), imipenem (IMP) and colistin (CO) were tested by standard disk diffusion method. The antimicrobial susceptibility to colistin and the MIC were determined with the E-test. The MDR-PA isolates were susceptible to ceftazidime, ciprofloxacin, amikacin and imipenem in 1, 5, 11 and 32%, respectively. There were 5 antimicrobial resistance patterns of MDR-PA: AK-CAZ-CIP-IMP (50%), AK-CAZ-CIP (32%), CAZ-CIP-IMP (11%), AK-CAZ-IMP (6%) and AK-CIP-IMP (1%). Colistin had good efficacy against MDR-PA (98% susceptibility rate). The MIC50 and MIC90 for colistin were 1.0 and 1.5 jig/ml, respectively. Only 2 MDR-PA isolates were resistant to colistin with the MICs of 3 and 12 microg/ml, respectively. The majority of MDR-PA isolates remained susceptible to colistin; therefore, colistin is a good option for treatment of MDR-PA.

Ciprofloxacin reduces occurrence of fever in children with acute leukemia who develop neutropenia during chemotherapy.

BACKGROUND: Fluoroquinolones reduce occurrence of fever in adult cancer patients who develop neutropenia, but there has been no randomized controlled trial in children, and there are only a few studies considering resistance in intestinal floral after ciprofloxacin has been used. METHODS: Children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20mg/kg/day or placebo from the beginning of their chemotherapy. Rectal swab cultures were taken before and at 1 and/or 2 weeks after the intervention. RESULTS: Of the total of 95 patients, 45 and 50 patients received ciprofloxacin and placebo, respectively. Of the 71 patients who developed neutropenia, the proportion of children who developed fever was significantly lower in the ciprofloxacin group than in the placebo group (17/34 [50.0%] versus 27/37 [73.0%]; absolute difference in risk, -23.0%; 95% confidence interval: -45.0% to -0.9%; P = 0.046). Ciprofloxacin significantly reduced the occurrence of febrile episodes in patients with acute lymphoblastic leukemia in the induction phase of chemotherapy, but not in patients with lymphoma or in the consolidation phase of chemotherapy. Adverse effects were not different between the groups. After intervention, the percentages of Escherichia coli and Klebsiella pneumoniae susceptible to ciprofloxacin were significantly lower in the ciprofloxacin group. CONCLUSION: Ciprofloxacin can prevent fever in neutropenic patients with acute lymphoblastic leukemia during the induction phase of chemotherapy with good tolerance and no serious side effects. Due to the selective pressure of intestinal flora resistance to ciprofloxacin, the long-term effectiveness needs further investigation.

Gut microbiota of children living in rural south Thailand and urban Singapore.

BACKGROUND: An imbalanced prevalence of allergic diseases occurs in the region of South East Asia. It has been suggested that a change in lifestyle associated with improved hygiene and modernization has altered the composition of human gastrointestinal microbiota, and hence susceptibility to allergy. METHODS: This cross-sectional study was designed to investigate the differences between fecal microbiota in children living in areas with contrasting socioeconomic development. Fecal samples from 73 young children (age 3.0 +/- 0.5) from rural Thailand and 69 age-matched children from urban Singapore were collected and studied using selective culture. Clinical data were also collected using modified ISAAC questionnaires, aiming to identify the key differences in the demographic as well as clinical features between the two study groups. RESULTS: The two contrasting populations studied differed significantly in multiple lifestyle factors such as family size, antibiotic use and sources of drinking water in the households. Rural children harbored significantly higher counts of lactic acid bacteria (LAB) [7.1 (6.4, 8.3) vs 6.0 (5.3, 7.0) logCFU/g, p < 0.001)], coliforms [8.9 (7.3, 10.2) vs 6.9 (5.7, 7.7) logCFU/g, p < 0.001)] as well as staphylococci [5.3 (4.8, 6.3) vs 4.3 (3.6, 5.0) logCFU/g, p < 0.001)] than their urban counterparts. However, enterococcal counts did not differ between the two groups. No single lifestyle factor could be identified to have caused such differences. CONCLUSIONS: Certain fecal microbial counts were higher in rural children compared with urban children in South East Asia. Several contrasting home environmental conditions and practices were also identified. These may serve as a basis for future investigation of lifestyle factors underlying the global gradient of the increasing trends of allergic diseases.

In vitro activity of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin combinations against ceftazidime-resistant Pseudomonas aeruginosa.

The effects of antimicrobial combinations against ceftazidime-resistant Pseudomonas aeruginosa strains isolated from hospitalized patients were investigated. Using the checkerboard titration method, combination of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin was synergistic against 4, 11, 38 and 39% of 22, 18, 29 and 18 strains tested respectively and additive effect of the combinations against the strains tested was 41, 33, 14 and 44%, respectively. Antagonistic effects against the isolates were noted when fosfomycin was combined with gentamicin (27%), ceftazidime (22%) and imipenem (7%). No antagonistic effect was observed in the ceftazidime-gentamicin combination.