To assess the frequency of extracellular superoxide (O2−) production by enterococci, multiple species were surveyed in a whole organism assay for their ability to reduce ferricytochrome c in a superoxide dismutase-inhibitable fashion. For stool and clinical enterococcal isolates and 12 type strains, only Enterococcus faecalis (87/91 isolates and ATCC 19443), Enterococcus faecium (5/13 isolates), Enterococcus casselijlavus (ATCC 25788), and Enterococcus gallinarum (ATCC 35038) produced extracellular O2−. Among 106 strains comprising 13 species of enteric gram-negative bacilli and gram-positive cocci, only Lactococcus lactis subspecies lactis produced extracellular O2−, Mean (±SE) rates of extracellular O2− production in vitro by E. faecalis for isolates associated with bacteremia and endocarditis and for isolates from stool were 2.4 ± 0.2, 1.9 ± 0.2, and 1.5 ± 0.3 nmol of O2− min−1 109 cfu−1, respectively (P = .025, analysis of variance), suggesting an association between invasiveness and extracellular O2− production.
Summary Invasive fungal infections (IFI) are frequent causes of mortality after allogeneic stem‐cell transplantation (SCT). A very important risk factor for IFI is the use of steroids. We used a risk‐based chemoprevention in an open‐labelled pilot study. All patients received oral fluconazole or itraconazole (200–400 mg day −1 ) during their neutropenic episode. Starting on day +30, patients receiving prednisone ≥30 mg day −1 were switched to twice weekly Amphotericin‐B‐lipid‐complex (ABLC) in a dose of 4 mg kg −1 . Patients receiving lower steroid doses continued on the fluconazole/itraconazole prophylaxis. Between 1999 and 2002, 100 patients were enrolled and followed for IFI for 1 year. Seven patients were started on therapeutic daily ABLC treatment before day +30 because of documented or suspected IFI; four had definite or probable aspergillosis, and two had candidaemia. Thirty patients did not need prophylactic ABLC; only one developed candidaemia. Sixty‐three patients received ABLC prophylaxis for a median of 52 days (range: 1–289). Seven of these patients developed IFI; one definite and two probable cases of aspergillosis, one case of probable Trichosporon beigelii infection, and three cases of candidaemia. The twice weekly ABLC was well tolerated. This risk‐based chemoprevention appears to be effective and might diminish the role of steroids as risk factor for IFI after allogeneic SCT. The relatively high incidence of early IFI suggests that additional prophylaxis for IFI may be indicated for poor‐risk patients prior to day +30.
Transthoracic echocardiography plays a pivotal role in the diagnosis of complications, evaluation of hemodynamics, and management of patients with surgically repaired congenital heart disease. Late complications of surgically corrected tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease, include pulmonary regurgitation (PR), ventricular septal defect (VSD) patch leakage, and residual right ventricular outflow tract obstruction. We present a case of severe PR secondary to Bartonella endocarditis in an adult with a history of repaired TOF in which echocardiography was instrumental in the diagnosis of severe PR, residual VSD, and a right-to-left shunt through an unsuspected patent foramen ovale.
An 81-year-old woman had pneumonia caused by Streptococcus pneumoniae (levofloxacin Etest minimum inhibitory concentration [MIC] 1.5 microg/ml) and was treated with intravenous gatifloxacin 200 mg/day. After 3 days of therapy, repeat sputum cultures were positive for S. pneumoniae, which was resistant to levofloxacin (Etest MIC > 32 microg/ml). The isolate obtained before therapy showed a preexisting parC mutation of aspartic acid-83 to asparagine (Asp83-->Asn), and the isolate obtained during therapy showed an acquired gyrA mutation from serine-81 to phenylalanine (Ser81-->Phe) and a second parC mutation from lysine-137 to Asn (Lys137-->Asn). Both isolates were the same strain, as determined with pulsed-field gel electrophoresis. This case demonstrates the potential for resistance to emerge during 8-methoxy fluoroquinolone therapy for fluoroquinolone-susceptible S. pneumoniae with a preexisting parC mutation. Additional clinical failures with a fluoroquinolone may occur unless these first-step parC mutants can be identified to assist clinicians in selecting appropriate antimicrobial therapy.
Invasive fungal infections (IFIs) are increasing after allogeneic stem cell transplantation (aSCT). Known prognostic factors for IFI include mismatched donors, severe GvHD, CMV infection, and the use of steroids. Our group treated all patients during their initial neutropenic episode with oral fluconazole or itraconazole (200–400 mg/day). Starting on day +30, patients who received prednisone≥ 30 mg/day were switched to intravenous amphotericin-B lipid complex (ABLC; Abelcet) at a dosage of 4 mg/kg twice a week. Patients who received lower steroid doses continued their fluconazole/itraconazole until at least day +100 after SCT. Between 1999 and 2002, a total of 100 patients were enrolled, including 24 patients with unrelated donors and 11 patients with partially mismatched related donors. Good-risk patients were a minority (27%), whereas 32% had overt relapse and/or refractory disease. Preparative regimens contained TBI (45%), busulfan/cyclophosphamide (35%), or fludarabine (20%). BM and PBSC were the source of stem cells in 43% and 57% of patients, respectively. Prophylaxis of aGvHD was based on cyclosporine but included steroids in 27%, in vivo T-cell depletion in 25%, and in vitro T-cell depletion in 15% of patients. Out of 37 patients who did not receive ABLC prophylaxis, 2 developed IFI beyond day +30 (1 from Aspergillus on day +36, 1 from Candida on day +63). A total of 63 patients did receive prophylactic ABLC for a median of 52 days (range, 1 to 289 days). Six of the patients at such high risk of IFI that they were assigned to ABLC prophylaxis still developed IFI (3 from Aspergillus at days +45, +65, and +255 and 3 from Candida at days +70, +72, and +210). An additional 2 patients had probable, but undocumented, IFI. Univariate analysis of all patients with IFI showed that factors increasing the risk of IFI were BM as the stem cell source, MUD or PMRD, severe GvHD, and CMV infection (P< .01 in all comparisons). Interestingly, the use of steroids (and/or use of ABLC) was no longer a prognostic parameter. The twice-weekly ABLC was well tolerated, with a median increase in creatinine of 0.85 mg/dL. This regimen of twice-weekly intravenous ABLC 4 mg/kg appears to compensate for the increased risk of IFI associated with the use of steroids after allogeneic SCT. This prophylaxis resulted in a low incidence of IFI in this analysis of 100 allograft recipients and allowed the use of higher doses of steroids. To increase its early efficacy, the twice-weekly ABLC prophylaxis perhaps should be started earlier than day +30.
Background: Prolonging the infusion of a β-lactam antibiotic enhances the time in which unbound drug concentrations remain above the minimum inhibitory concentration (fT>MIC). Objective: To compare the pharmacodynamics of several dosing regimens of piperacillin/tazobactam administered by intermittent and prolonged infusion using pharmacokinetic data from hospitalized patients. Methods: Steady-state pharmacokinetic data were obtained from 13 patients who received piperacillin/tazobactam 4.5 g every 8 hours, infused over 4 hours. Monte Carlo simulations (10,000 pts.) were performed to calculate pharmacodynamic exposures at 50% fT>MIC for 4 intermittent-infusion regimens (3.375 g every 4 and 6 h, 4.5 g every 6 and 8 h) and 4 prolonged-infusion regimens (2.25 g, 3.375 g. 4.5 g, and 6.75 g every 8 h [4-h infusion]) of piperacillin/tazobactam using pharmacokinetic data for piperacillin. Cumulative fraction of response (CFR) was calculated using MIC data for 6 gram-negative pathogens (Meropenem Yearly Susceptibility Test Information Collection, 2004-2007), and probability of target attainment (PTA) was calculated at MICs ranging from 1 μg/mL to 64 μ/g/mL Results: The CFR for 3.375 g every 4 hours (intermittent infusion) and 3.375–4.5 g every 8 hours (prolonged infusion) greater than or equal to 90.3% for Escherichia coli, Serratia marcescens, and Citrobacter spp. Increasing the prolonged-infusion dose to 6.75 g improved the CFR to greater than 90% for Enterobacter spp. For every regimen evaluated, the CFR was less than 90% for Klebsiella pneumoniae and Pseudomonas aeruginosa. At an MIC of 16 μg/mL, PTA was greater than 90% for one intermittent-infusion regimen (3.375 g every 4 h) and 3 prolonged-infusion regimens (≥3.375 g every 8 h). but no regimen achieved a PTA greater than 90% at an MIC of 64 μ/g/mL. Conclusions: At doses greater than or equal to 3.375 g every 8 hours, 4-hour infusions of piperacillin/tazobactam achieved excellent target attainment with lower daily doses compared with standard regimens at MICs less than or equal to 16 μg/mL
