Nine of 56 (20% actuarial) patients receiving a T celldepleted, HLA-identical sibling BMT for hematological malignancy developed hemorrhagic cystitis (HC) 15-368 days post BMT. Hematuria was severe and prolonged (median duration 18 days). In eight patients (89%), a viral etiology was confirmed (four adenovirus, four polyomavirus). HC was associated with significant morbidity, with all patients requiring continuous bladder irrigation and transfusion support for blood loss and thrombocytopenia. HC occurring before day 100 was significantly associated with a reduction in longterm survival: 1/7 (14.3%) patients developing HC before day 100 became long-term survivors vs 21/49 (42.8%) without HC by day 100 (P = 0.034). In univariate analysis, HC was associated with a diagnosis of multiple myeloma (P = 0.02). There was a trend towards a higher incidence of HC in patients reactivating cytomegalovirus (CMV) compared with those remaining CMV negative (18.4 vs 5.5% respectively, P = 0.17). HC was not associated with graft-versus-host disease, or with the transplant dose of CD34 + progenitors or CD3 + cells, patient age or sex. Life-threatening, viral-induced HC and the unusually high incidence of adenovirus-induced HC may have been caused by immune deficiency associated with T cell depletion in this series.

To benchmark the activity of moxifloxacin (a newer fluoroquinolone), a U.S. study comprising 16,141 contemporary isolates of Streptococcus pneumoniae (5,640), Haemophilus influenzae (6,583), and Moraxella catarrhalis (3,648) referred from 377 institutions during 1998 is described. For S. pneumoniae the modal MIC and MIC at which 90% of the isolates were inhibited (MIC 90 ) for moxifloxacin were 0.12 and 0.25 g/ml, respectively, independent of susceptibility to other drug classes, geography, or site of infection. Eleven isolates were intermediate or resistant to levofloxacin and grepafloxacin; of these isolates, 1 remained susceptible to sparfloxacin, 2 remained susceptible to moxifloxacin, and 4 remained susceptible to trovafloxacin. All 11 isolates possessed classic mutations in gyrA and/or parC known to confer reduced susceptibility to fluoroquinolones. Four isolates (originating from four separate states) belonging to a multidrug-resistant, fluoroquinolone-resistant clone were identified by pulsed-field gel electrophoresis. For moxifloxacin and trovafloxacin, at least 87% of isolates demonstrated MICs >3 twofold concentrations below the susceptibility breakpoints, in contrast to no more than 15% for levofloxacin, grepafloxacin, and sparfloxacin. Of the isolates that were multidrug resistant (7.4%), >98% remained susceptible to moxifloxacin. The modal MIC and MIC 90 for M. catarrhalis (both 0.06 g/ml) and for H. influenzae (both 0.03 g/ml) were independent of ␤-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future studies.In recent years, increasing antibiotic resistance among bacteria causing infections within both the hospital and community environments has severely compromised our ability to successfully treat patients empirically. Perhaps nowhere is this more apparent than with patients presenting with communityacquired respiratory tract infections (CA-RTI), in which Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are common pathogens (6). The emergence and dissemination of penicillin-resistant pneumococci are now global phenomena (1,4,14,22,36) and continue to increase. Compounding the problem is the tendency for organisms to also be refractory to some cephalosporins and macrolides (11,42). Similarly, resistance caused by the widespread acquisition of plasmid-encoded BRO1 and/or BRO2 ␤-lactamase in M. catarrhalis and of TEM-1 enzyme in H. influenzae (13, 35) has effectively removed ampicillin and amoxicillin used alone as therapeutic choices for ␤-lactamase-producing isolates, neither being stable in the presence of those enzymes. Together, these factors have created a need for alternative oral candidate drugs for use as empiric therapies for patients with CA-RTI.Recently, the further evolution of the fluoroquinolone class of drugs has resulted in a number of new compounds with an expanded spectrum of activity compared with earlier compounds such as ciprofloxacin and ofloxacin, most significantly against S. pneumo...

Levofloxacin had comparable activity to the other agents tested against the atypical respiratory pathogens, confirming its potential as an alternative for empirical therapy of community-acquired pneumonia.

No abstract