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

No abstract

Although CMV disease appears to be less frequent in children than adults, CMV infection still contributes significantly to morbidity and mortality in this population, especially when combined with severe immunosuppression.

Immunofluorescence staining of centrifugation-enhanced shell vial (SV) cultures for respiratory viruses (RV) after 24 h of incubation, rather than the more commonly prescribed times of 48 h and 5 days, allowed for the detection of 77% of the RV-positive specimens that would ordinarily not have been detected as positive until 48 h. Staining SVs at 24 h also permitted earlier detection of viruses that were missed by rapid antigen detection methods.Respiratory viruses (RV) can cause a wide variety of human disease. Detection by the diagnostic virology laboratory of these viruses in clinical specimens may impact on the medical management of the patient and can be of epidemiological importance. Many virology laboratories detect RV by inoculating conventional cell culture tubes with respiratory samples and then examining for cytopathic effect and/or hemadsorption. This procedure, however, can require many days or even weeks for viral detection and identification, providing culture results to clinicians in a period of time that may not be clinically useful.Laboratory diagnosis of RV infections has become easier and more rapid with the use of centrifugation-enhanced shell vials (SV) as the culture method. Centrifugation of the clinical specimen onto cell monolayers followed by immunofluorescence detection and identification of viral antigens in SV cultures allows a much earlier diagnosis of infection. Since it was first described for the rapid detection of cytomegalovirus (2), the SV method has been successfully used to rapidly detect RV infections (6, 7). However, what the optimal times are to stain SV cultures for RV is unclear. Many laboratories have felt, as we have, that staining at 48 h, and if negative, again at 5 days, would allow the most sensitive and cost-effective early detection of an RV. However, pressure for an even earlier detection is often placed upon the laboratory by clinicians, most especially when immunocompromised patients are involved, so that clinically relevant decisions can be made. This study assessed the value of immunofluorescence staining of SV cultures for RV at 18 to 24 h compared with 48 h and 5 days to determine whether such a procedure would allow a more rapid detection and reporting of positive clinical specimens.

An increase in shell vial centrifugation force to 3,500 x g and a concomitant reduction in spin time to 15 min did not decrease the sensitivity of detecting viruses in clinical specimens compared with the accepted practice of using 700 x g for 40 min. No damage to the cell monolayer (ML) at the higherg force was observed. Toxicity to the ML is decreased with the shorter spin, probably because of reduced time of contact between the specimen and the ML.