Evaluation of aztreonam in the treatment of severe bacterial infections.

We investigated the clinical efficacy and safety of aztreonam in the treatment of 50 episodes of infection in 46 adult patients. The clinical condition of patients at the beginning of treatment was critical or poor in 28 of the episodes of infection. Episodes treated were 39 urinary tract infections (12 of them with concomitant bacteremia), 2 soft tissue infections, 8 patients with osteomyelitis (1 with concomitant bacteremia), and one episode of pneumonia. Significant isolated microorganisms were aerobic or facultative gram-negative rods and were responsible for the following episodes of infection (number of episodes): members of the family Enterobacteriaceae (49), Pseudomonas aeruginosa (5), and Haemophilus influenzae (1). The overall rate of clinical response to aztreonam was 94% of the treated episodes. Colonization or superinfection or both occurred in 29 episodes, but only 8 episodes required antimicrobial therapy. Aztreonam seems to be an effective single agent therapy for many bacterial infections. Colonization and superinfection by Candida sp., Streptococcus faecalis or Staphylococcus aureus must be monitored.     

Comparison of ceftazidime concentrations in bile and serum.

Biliary excretion of ceftazidime, a new broad-spectrum cephalosporin, was studied in two groups of patients after administration of a 2-g dose intravenously. Group A included 10 patients in whom ceftazidime levels in bile were measured during cholecystectomy. Group B included 10 patients with indwelling biliary tubes in whom ceftazidime levels in bile and serum were simultaneously measured at 0.5, 1, 2, 4, 6, and 8 h after administration of the drug. Although ceftazidime levels were variable, they exceeded the minimal inhibitory concentrations of most biliary tract pathogens in both groups.     

Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin

Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomially acquired, antibiotic-associated diarrhea. The drugs most commonly used to treat diseases associated with C. difficile are metronidazole and vancomycin. Most clinical laboratories assume that all C. difficile isolates are susceptible to metronidazole and vancomycin. We report on the antimicrobial susceptibilities of 415 C. difficile isolates to metronidazole and vancomycin over an 8-year period (1993 to 2000). The overall rate of resistance to metronidazole at the critical breakpoint (16 microg/ml) was 6.3%. Although full resistance to vancomycin was not observed, the overall rate of intermediate resistance was 3.1%. One isolate had a combination of resistance to metronidazole and intermediate resistance to vancomycin. Rates of resistance to metronidazole and vancomycin were higher among isolates from human immunodeficiency virus-infected patients. Molecular typing methods proved the absence of clonality among the isolates with decreased susceptibilities to the antimicrobials tested.     

Comparative in vitro activity of the new quinolone gemifloxacin (SB-265805) with other fluoroquinolones against respiratory tract pathogens

The in vitro activity of gemifloxacin (SB-265805) was compared with that of other fluoroquinolones against 302 clinical isolates of Streptococcus pneumoniae, 300 clinical isolates of Haemophilus influenzae and 28 clinical isolates of Moraxella catarrhalis, including multiply resistant strains. Gemifloxacin at 0.12 mg/L inhibited all microorganisms tested. MIC(90) values of gemifloxacin, trovafloxacin, grepafloxacin and levofloxacin against all (630) isolates tested were 0.03, 0.12, 0.12 and 1 mg/L, respectively. MIC(90) values of the same fluoroquinolones against S. pneumoniae were 0.06, 0.25, 0.12 and 1 mg/L, respectively.     

Effect of Milling on Particle Shape and Surface Energy Heterogeneity of Needle-Shaped Crystals

Purpose

Milling and micronization of particles are routinely employed in the pharmaceutical industry to obtain small particles with desired particle size characteristics. The aim of this study is to demonstrate that particle shape is an important factor affecting the fracture mechanism in milling.

Methods

Needle-shaped crystals of the β polymorph of D-mannitol were prepared from recrystallization in water. A portion of the recrystallized materials was ball-milled. Unmilled and milled sieved fractions of recrystallized D-mannitol were analyzed by dynamic image analysis (DIA) and inverse gas chromatography (IGC) at finite concentration to explain the breakage/fracture behavior.

Results

In the process of ball-milling, D-mannitol preferentially fractured along their shortest axis, exposing (011) plane with increased hydrophilicity and increased bounding rectangular aspect ratio. This is in contrary to attachment energy modeling which predicts a fracture mechanism across the (010) plane with increased hydrophobicity, and small change in particle shape.

Conclusions

Crystal size, and more importantly, crystal shape and facet-specific mechanical properties, can dictate the fracture/cleavage behavior of organic crystalline materials. Thorough understanding of the crystal slip systems, combining attachment energy prediction with particle shape and surface characterization using DIA and IGC, are important in understanding fracture behavior of organic crystalline solids in milling and micronization.     

Isolation of Mycobacterium tuberculosis strains with a silent mutation in rpoB leading to potential misassignment of resistance category

Our study provides an alert regarding the transmission of rifampin-susceptible strains of Mycobacterium tuberculosis with a silent substitution in codon 514 of rpoB. Among 1,450 cases, we identified 12 isolates sharing this mutation and related restriction fragment length polymorphism (RFLP) types. The mutation impaired hybridization with the wild-type probes in three independent commercial assays, which could lead to misassignment of resistance.     

Outcomes of New Quality Standards of Follitropin Alfa on Ovarian Stimulation

Background

Human follicle-stimulating hormone (hFSH; follitropin alfa) can be employed therapeutically to induce ovarian follicular development in assisted reproduction treatments. Current recombinant hFSH (r-hFSH) preparations available for clinical use are labeled either in terms of the bioactivity expressed in international units (IU) or in mass (μg). Several clinical trials have tried to assess the clinical implications of the physicochemical improvements in the dosing of follitropin alfa filled by mass (FbM). The aim of this study was to perform a meta-analysis of previous studies in order to assess the efficacy and safety of ovarian stimulation using follitropin alfa FbM compared with follitropin alfa filled by international units (FbIU).

Methods

A literature search was carried out in scientific databases to find published articles and abstracts comparing both hormone preparations. A fixed effects model meta-analysis was performed. The variables studied include the average dose (IU), days of treatment, estradiol peak, follicles >14 mm, number of extracted oocytes, number of embryos obtained, number of cases of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancies.

Results

A total of six studies met the stated criteria and were included in the meta-analysis. In these studies, the average r-hFSH dose per patient was 230.29 IU less with administration of follitropin alfa FbM compared with FbIU, and the number of days of treatment was reduced by 0.48. In addition, a significantly greater number of oocytes (0.84) were extracted, more embryos (0.88) were obtained, and a higher peak level of estradiol (613.08 pmol/L) was achieved in the patients undergoing ovarian stimulation with follitropin alfa FbM. However, no statistically significant differences were observed in the number of follicles >14 mm, clinical pregnancies, or OHSS cases.

Conclusion

Follitropin alfa FbM, a technologically modified formulation of r-hFSH, is as safe as follitropin alfa FbIU but requires a smaller dose over a shorter period to produce more oocytes and final embryos.     

Fever of unknown origin in solid organ transplant recipients

Fever is a common clinical manifestation in transplant patients, and it may be due to many different reasons. In the general population, infections and malignancies as causes of fever of unknown origin (FUO) have decreased over time, whereas inflammatory diseases and undiagnosed fevers have increased. This article reviews FUO in transplant patients, despite there being no clear and widely accepted definition of FUO for such patients. The methodology of diagnosis has been accelerated and made more accurate, not only for the imaging diagnosis but also for microbiology. With respect to diagnosis of FUO in the transplant patient population, consideration should be given to the specific type of transplant patient, to the results of the physical examination, and to the epidemiological antecedents. This article examines an approach that considers different syndromes, followed by an etiologically oriented differential diagnosis.     

BK Virus in Liver Transplant Recipients: A Prospective Study

Background

BK virus (BKV) is a polyomavirus that is associated with nephropathy and graft loss among kidney transplant recipients. The role of BK virus in nonrenal solid organ transplant recipients has not been clearly established; only anecdotal case reports have been published.

Methods

From August 2005 to September 2007, all orthotopic liver transplant (OLT) recipients who gave their consent were enrolled in this prospective longitudinal study. BK viral load was measured using real-time quantitative polymerase chain reaction assays of urine and plasma, using samples collected at week 1 and months 1, 3, 6, 9, 12, 15, 18, 21, and 24 posttransplantation. We also collected demographic and clinical data, including serum creatinine and immunosuppressive therapy.

Results

The mean age of the 62 patients was 51.4 years including 14 (22.5%) women. Hepatitis C infection was present in 24 patients (38.7%). BK viruria was detected in 14.5% of 290 samples, corresponding to 13 patients (21%). BK viremia was detected in 5.1% of 317 samples, corresponding to 11 patients (18%). Almost all cases of BK viremia (91%) occurred in the first 3 months after OLT. BK viremia was more common among patients experiencing a rejection episode (10.6 vs 40%, P = .01). We did not observe a relationship between single episodes of BKV replication and renal function: median plasma creatinine 1.1 mg/dL in patients without versus 1.2 mg/dL with BK viremia. The three patients with persistent viremia displayed renal insufficiency; one of them died due to multiorgan failure of unknown origin.

Conclusions

BKV is frequently detected in OLT recipients (viruria 21% and viremia 18%) early after transplantation. It is more common among patients with rejection episodes. Persistent BK viremia may be related to renal dysfunction in OLT patients.