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Beta-lactam-resistant Enterobacteriaceae represent an important public health problem; however, questions exist about their prevalence and the impact of recent breakpoint changes on clinical practice. We surveyed infectious disease physicians to better understand these issues. Many reported encountering resistant Enterobacteriaceae; respondents generally favored a more conservative interpretation of antimicrobial susceptibility results., (Published by Elsevier Inc.)

Background: Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens., Methods: Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7-21 days. The primary end point was clinical response at follow-up/test-of-cure visit., Results: A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval [CI] for the difference, -5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, -4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, -0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, -7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%)., Conclusions: The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens.

Twenty-eight patients with skeletal infections due to Pseudomonas aeruginosa were treated with aztreonam during two open, noncomparative, multicenter clinical trials. Ten patients with septic arthritis received 2 g of aztreonam three times a day (modal) for 30 days (mean). The mean follow-up period was 4 weeks. Microbiologic cure was achieved in all 10 patients; complete clinical cure, in eight; and partial clinical cure, in two. Eighteen cases of osteomyelitis were treated with 2 g of aztreonam three times a day (modal) for 40 days (mean), with a mean follow-up period of 6 months. Microbiologic cure was achieved in 17 patients. Relapse occurred 1 month after therapy in one patient. Complete clinical cure was achieved in 13 and partial clinical cure was achieved in five patients. The most common adverse reactions to aztreonam were a transient elevation in levels of hepatic enzymes and transient eosinophilia. Three superinfections and one subsequent infection occurred. These results support use of aztreonam for the treatment of skeletal infections due to P. aeruginosa.

Aztreonam was administered to 122 patients with presumptive or confirmed gram-negative bacillary meningitis in an open, multinational study. The antibiotic was administered at a dosage of 1-2 g to adults, 50 mg/kg to children greater than 2 years old, and 30 mg/kg to infants three or four times daily. Seventy-seven patients had microbiologically confirmed gram-negative meningitis due to an aztreonam-susceptible organism and received aztreonam for at least 48 hours. Haemophilus influenzae was the most frequently recovered pathogen (40 patients), followed by Enterobacteriaceae (16 patients), Neisseria meningitidis (15 patients), and Pseudomonas species (six patients). All but four patients were microbiologically cured. Microbiologic failure was associated with either a persistent intracerebral abscess (one patient) or a foreshortened course of therapy before microbiologic reevaluation and death (at 48 hours, 48 hours, and 72 hours after initiation of treatment, respectively). These data suggest that aztreonam is effective in the treatment of gram-negative bacillary meningitis caused by susceptible organisms.

Over an 18-month period, the incidence of group A beta-hemolytic streptococcal bacteremia rose from an average of 2.5 per 10,000 patient discharges to 17.9. A retrospective analysis was performed comparing patients with group A beta-hemolytic streptococcal bacteremia during this 18-month period with those who presented over the preceding 36 months. Most of the increased incidence was attributable to individuals hospitalized with a diagnosis of drug addiction who had concomitant soft-tissue infection, although the absolute number of hospitalized drug addicts did not change during this interval. No common or distinctive group A streptococcal serotypic patterns were discovered. This experience suggests that group A beta-hemolytic streptococcal bacteremia and soft-tissue infection may present in epidemic fashion among parenteral drug addicts in the absence of a common source.

An elderly man had group B streptococcal meningitis. The infection may have seeded the meninges through a rhinocerebral fistula. Despite the frequency of nasopharyngeal colonization with this organism, reports of adult meningitis secondary to group B Streptococcus are rare; to our knowledge, no previous cases specifically associated with rhinocerebral fistula have been described. Reasons for the discrepancy between the frequency of nasopharyngeal colonization and the rarity of meningitis are suggested.

Patients enrolled in two double-blind multicenter studies were evaluated for the development of hypoprothrombinemia during treatment with cephalosporins. Patients with pneumonia or peritonitis received ceftizoxime, cefotaxime, or moxalactam. The incidence of hypoprothrombinemia was greater in patients with peritonitis (12 of 49) than in those with pneumonia (5 of 96; P less than 0.05). Overall, moxalactam was associated with a higher incidence of hypoprothrombinemia (13 of 52) than either ceftizoxime (1 of 43; P less than 0.05) or cefotaxime (3 of 50; P less than 0.05), and moxalactam patients incurred the highest average increase in prothrombin time (3.7 s) as compared with either ceftizoxime (0.5 s; P less than 0.05) or cefotaxime (0.9 s; P less than 0.05) patients. The occurrence of hypoprothrombinemia in moxalactam patients with peritonitis was not related to dosage, duration of therapy, age, sex, race, or renal or hepatic function. The degree of ileus was, however, strongly related to the development of coagulopathy in moxalactam-treated patients only.

The adherence of granylocytes to surfaces, measured in vitro in nylon fiber columns, is inhibited by in vivo administration of anti-inflammatory agents. Therefore, the effect of inflammation itself was assessed in blood from patients with acute inflammatory diseases. Mean adherence in these patients was twice normal (56.4 +/- 5.6% vs. 29.4 +/- 5.2%); their plasma contained a factor that augmented adherence of normal cells to 47.5 +/- 5.6% whereas the patient's cells showed a normal level of adherence (34.0 +/- 6.8%) when resuspended in normal plasma. Although exudate fluid from exprimental inflammation also contained the augmenting factor, cells from the exudate maintained their high level of adherence after washing and suspension in normal plasma. The augmenting factor detected in plasma from patients with inflammation was not present in serum and was inactivated by heating plasma to 56 degrees C for 30 min; restoration of augmenting activity was accomplished by addition of 20% guinea pig serum to the heat-treated plasma. Because the guinea pig serum itself did not increase adherence when added to normal plasma, it appears that the augmenting factor is heat-stable, but requires a heat-labile cofactor like complement. Sephadex G-200 fractionation of inflammatory plasma showed adherence-augmenting activity in the majority of fractions, with peak activity in the fractions corresponding to approximate molecular wts of 30,000, 160,000 and 400,000.

A retrospective single blind study was conducted to compare the efficacy of crossed-immunoelectrophoresis using concanavalin A intermediate gel with double immunodiffusion tests in the diagnosis of invasive candidiasis. On the basis of cytoplasmic antibody detection, crossed-immunoelectrophoresis with concanavalin A differentiated reliably between Candida albicans fungemia and invasive candida infection, whereas double immunodiffusion did not. With regard to sensitivity, specificity, and predictive value crossed-immunoelectrophoresis with concanavalin A was superior to double immunodiffusion. Analysis of double immunodiffusion precipitin bands revealed fuzzy and sharp precipitin bands which corresponded to mannan (fuzzy) and cytoplasmic (sharp) antibodies in the crossed-immunoelectrophoresis with concanavalin A assay. Therefore, the finding of sharp bands in the double immunodiffusion procedure supports the diagnosis of invasive candidiasis.

Cefonicid is a parenteral cephalosporin with a half-life of 4.5 hours, which permits once-daily dosing. The efficacy of cefonicid in the treatment of established staphylococcal infections was reviewed in all patients with infections due to staphylococci who were treated with cefonicid during the US clinical development program. Two hundred evaluable cases were identified, of which 95 had other pathogens as well. Cefonicid was clinically effective in 92% of skin and soft tissue infections, 74% of bone and joint infections, 83% of respiratory tract infections, and 95% of urinary tract infections. None of the three evaluable patients with Staphylococcus aureus endocarditis responded to cefonicid. Thus, based on current evidence, cefonicid is not effective in the treatment of established staphylococcal endocarditis. However, for the treatment of staphylococcal infections at other sites, cefonicid is comparable to other cephalosporins, most of which must be administered more frequently than cefonicid and thus are less cost-effective.

Despite in vitro demonstrations of synergism against enterococci, combinations of cephalosporin and aminoglycoside antibodies have been ineffective in the therapy of enterococcal endocarditis. Penicillin-gentamicin, cephalothin-gentamicin, and cefazolin-gentamicin were used to treat enterococcal endocarditis in rabbits. A direct relation was observed between the rate of cure and the degree by which the peak serum concentration of penicillin and the cephalosporins exceeded the minimal inhibitory concentration of the enterococcus. Thus, cephalosporin doses which produce serum concentrations which exceed the minimal inhibitory concentration of the enterococcus by several orders of magnitude may, in combination with aminoglycosides, be effective in treating human enterococcal endocarditis.