Bilirubin levels predict renal cortical changes in jaundiced neonates with urinary tract infection.

BACKGROUND: This study was undertaken to determine the incidence of urinary tract infection (UTI) and the frequency of anatomical abnormalities in newborns with unexplained jaundice and to find out if there is any correlation between bilirubin level and renal damage. METHODS: We studied 462 full-term neonates for UTI. They were aged 3-25 days, with either high (>10 mg/dL) or prolonged (>10 days) hyperbilirubinemia, with or without manifestations such as fever, vomiting, diarrhea, poor feeding, lethargy, and irritability. Neonates positive for UTI were further investigated with ultrasound, cystourethrography, and acute phase renal scintigraphy with technetium-99m dimercaptosuccinate acid (DMSA). RESULTS: Thirty neonates (6.5%) were found to have UTI. Twenty-eight of them had indirect hyperbilirubinemia and two had direct hyperbilirubinemia, with total bilirubin levels of 11.8-20.1 mg/dL. None of the neonates was found to have jaundice because of other reasons such as infection. Vesicoureteral reflux was found in 5 neonates and one of them was combined with hydronephrosis. Renal scintigraphy with technetium-99m DMSA showed renal cortex changes in 14 (46.7%) of the 30 neonates with UTI. These 14 neonates also had increased levels of bilirubin in comparison to those with normal findings of DMSA. CONCLUSIONS: The incidence of UTI in uncomplicated neonatal jaundice is relatively high. Anatomical abnormalities of the urinary tract are not rare in infected children. Increased bilirubin levels are related to pathological findings in renal scintigraphy.

Comparative pharmacodynamic interaction analysis between ciprofloxacin, moxifloxacin and levofloxacin and antifungal agents against Candida albicans and Aspergillus fumigatus.

OBJECTIVES: Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Ciprofloxacin, a carboxyfluoroquinolone, was previously observed to demonstrate the pharmacodynamic interactions with antifungal agents by altering their growth inhibitory activity against Candida albicans and Aspergillus fumigatus. However, little is known about the interaction between other extended-spectrum fluoroquinolones, such as levofloxacin and moxifloxacin, and antifungal agents against C. albicans and A. fumigatus. METHODS: Using a microdilution chequerboard technique, we employed isobolographic analysis adapted to incorporate a non-active agent in order to analyse the potential in vitro interaction between ciprofloxacin, levofloxacin or moxifloxacin and the following representative antifungal agents: amphotericin B, fluconazole or voriconazole and caspofungin. RESULTS: Synergistic interactions [interaction indices (Iis) 0.69-0.83, P < 0.05] were observed between amphotericin B (0.07-0.31 mg/L) and either ciprofloxacin (0.19-7.65 mg/L) or levofloxacin (0.41-32.88 mg/L) against C. albicans and A. fumigatus. Synergy (Iis 0.56-0.87, P < 0.05) also was found between voriconazole (0.09-0.14 mg/L) and ciprofloxacin (0.22-11.41 mg/L) as well as between caspofungin (8.94-22.07 mg/L) and levofloxacin (0.14-5.17 mg/L) against A. fumigatus. Some antagonistic (Iis 1.16-1.29, P < 0.05) interactions were observed between fluoroquinolones and fluconazole against C. albicans. In general, ciprofloxacin enhanced the activity of antifungal agents more than moxifloxacin and levofloxacin against both C. albicans and A. fumigatus. CONCLUSIONS: The knowledge of the pharmacodynamic interactions between fluoroquinolones and antifungal agents may guide selection and potentially improve the outcome of immunosuppressed patients with concurrent bacterial and fungal infections.

Isobolographic analysis of pharmacodynamic interactions between antifungal agents and ciprofloxacin against Candida albicans and Aspergillus fumigatus.

Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 microg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis.