Activity of faropenem against resistant isolates of Streptococcus pneumoniae.

An in vitro study of the activity of 9 agents against 181 US pediatric isolates of Streptococcus pneumoniae identified imipenem and faropenem as the most active agents. Overall, faropenem was the most potent oral agent inhibiting 98% of isolates at 1 microg/mL.

Activity of oral agents against pediatric isolates of Streptococcus pneumoniae.

An in vitro study of the activity of 10 oral agents against 153 pediatric isolates of Streptococcus pneumoniae identified moxifloxacin and levofloxacin as the most active agents regardless of penicillin or macrolide susceptibility. Moxifloxacin inhibited all strains at 0.25 microg/ml and was 8- to 16-fold more potent than levofloxacin.

Severe intrauterine herpes simplex disease with placentitis in a newborn of a mother with recurrent genital infection at delivery.

We present a case of fatal herpes simplex type 2 (HSV-2) in a premature infant born to a mother diagnosed with recurrent HSV-2, based on history and HSV serology results. It was clinically evident at delivery, and subsequently confirmed by laboratory studies that the infant was infected before delivery. There was histopathologic evidence of placentitis and chorioamnionitis upon examination of the placenta and fetal membranes. This case illustrates a relatively uncommon complication of recurrent genital herpes at delivery--intrauterine transmission to the fetus from a primary episode during pregnancy.

Varicella vaccine.

Varicella vaccine is safe, effective, and cost-effective in healthy children, adolescents, and adults. Breakthrough cases of MVLS are significantly milder than wild-type varicella infection. No severe adverse events have been reported following vaccination, and the incidence of herpes zoster is less in vaccinees than in individuals who have had natural varicella infections. To date, there is no evidence waning immunity following vaccination. "New and improved" varicella vaccines that may be more effective than the current vaccine and can be stored at refrigerator temperatures may soon become available in the United States.

Activity of moxifloxacin against pathogens with decreased susceptibility to ciprofloxacin.

A panel of 279 clinical isolates of Gram-positive cocci and Gram-negative bacilli with varying levels of resistance to ciprofloxacin were analysed for susceptibility to moxifloxacin, ciprofloxacin, ofloxacin and nalidixic acid. Moxifloxacin was eight- to 32-fold more potent than ciprofloxacin and ofloxacin against staphylococci and Streptococcus pneumoniae, and equivalent to eight-fold more potent against enterococci. Although ciprofloxacin was intrinsically more potent than the other quinolones against highly susceptible Gram-negative isolates, the percentages of Gram-negative isolates susceptible to 1 mg/L of moxifloxacin or ciprofloxacin, or 2 mg/L of ofloxacin were 78%, 80% and 76%, indicating in-vitro equivalence of the agents against a collection that included isolates with diminished quinolone susceptibility. Staphylococci were analysed according to their ciprofloxacin susceptibility status. As ciprofloxacin resistance increased to high levels, all quinolone MICs increased, but moxifloxacin and ofloxacin MICs increased less than ciprofloxacin MICs. In mutational studies moxifloxacin inhibited more mutants (69%) at a concentration of 1 mg/L than did ciprofloxacin (63%) at 1 mg/L or ofloxacin at 2 mg/L (31%). The study indicated that moxifloxacin is more potent than ciprofloxacin and ofloxacin against Gram-positive pathogens, may be comparable in activity against less quinolone-susceptible Gram-negative isolates (other than Pseudomonas aeruginosa), and is less affected than ciprofloxacin by mechanisms responsible for increasing quinolone resistance in staphylococci.

In-vitro activity of levofloxacin against Streptococcus pneumoniae with various levels of penicillin resistance.

This in-vitro study was designed to compare the activity of levofloxacin with that of ciprofloxacin, ofloxacin, erythromycin, penicillin, amoxycillin, loracarbef, cefaclor, cefpodoxime, ceftriaxone, trimethoprim-sulphamethoxazole, clindamycin and vancomycin against a collection of 202 Streptococcus pneumoniae isolates (56% susceptible to penicillin, 34% intermediate, 10% resistant). The isolates (60% nasopharyngeal, 40% middle ear) were obtained from otherwise healthy children at child care centres in urban and rural Nebraska, and at a paediatric clinic in rural Kentucky. MICs were determined by NCCLS agar dilution methodology using an inoculum of 10(4) cfu/spot. Using NCCLS breakpoints, the percentage of penicillin-intermediate and -resistant strains susceptible to the evaluable agents were, respectively, as follows: levofloxacin (99%, 100%), ofloxacin (87%, 100%), erythromycin (52%, 65%), ceftriaxone (93%, 25%), trimethoprim-sulphamethoxazole (7%, 0%), clindamycin (93%, 100%) and vancomycin (100%, 100%). Without NCCLS interpretive criteria, no conclusions could be made concerning the susceptibility of penicillin-intermediate and -resistant strains to the other study drugs. All beta-lactam antibiotics, erythromycin and trimethoprim-sulphamethoxazole were less active against penicillin-resistant strains, indicating that these may be suboptimal agents for empirical therapy for suspected S. pneumoniae infections in these patient populations. However, levofloxacin, ofloxacin, clindamycin and vancomycin were equally active against penicillin-susceptible and -resistant strains. These data suggest that the efficacy of levofloxacin should be examined in both adult and paediatric S. pneumoniae infections involving body sites where levofloxacin concentrations > 2 mg/L can be achieved safely.

Rationale behind high-dose amoxicillin therapy for acute otitis media due to penicillin-nonsusceptible pneumococci: support from in vitro pharmacodynamic studies.

To evaluate whether increased doses of amoxicillin should be used to treat acute pneumococcal otitis media, an in vitro pharmacokinetic model was used to evaluate the killing of pneumococci by amoxicillin when middle ear pharmacokinetics were simulated. Logarithmic-phase cultures were exposed to peak concentrations of 3, 6, and 9 microg of amoxicillin per ml every 12 h, and an elimination half-life of 1.6 h was simulated. Changes in viable bacterial counts were measured over 36 h. All three doses rapidly decreased the viable bacterial counts of penicillin-susceptible strains below the 10-CFU/ml limit of detection by 6 to 10 h and maintained counts below this limit through 36 h. The 3-microg/ml peak dose was much less effective against two of three strains with intermediate penicillin resistance and all three penicillin-resistant strains, with bacterial counts approaching those in drug-free control cultures by 12 h. The 6-microg/ml peak dose completely eliminated two of three strains with intermediate penicillin resistance and maintained viable counts of the other nonsusceptible strains at 1.5 to 2 logs below the initial inoculum through 36 h. The 9-microg/ml peak dose was most effective, completely eliminating all three strains with intermediate penicillin resistance and maintaining the viable counts of the resistant strains at 3 to 4 logs below the original inoculum. The pharmacodynamics observed in this study suggest that peak concentrations of amoxicillin of 6 to 9 microg/ml may be sufficient for the elimination of penicillin-nonsusceptible pneumococcal strains causing otitis media, especially those with intermediate resistance to amoxicillin. In vivo pharmacokinetic studies are needed to determine if these levels can be achieved in middle ear fluid with amoxicillin at 70 to 90 mg/kg/day divided into two daily doses. If these levels are reliably achieved, then clinical studies are warranted.

Trovafloxacin, a new fluoroquinolone with potent activity against Streptococcus pneumoniae.

An in vitro study of the activity of 15 antibacterial agents against 202 recent pediatric isolates of Streptococcus pneumoniae from urban and rural Nebraska and rural Kentucky identified trovafloxacin, ofloxacin, clindamycin, and vancomycin as the most active agents and equally active against both penicillin-susceptible and--resistant strains. In contrast, six beta-lactams, three macrolides, and trimethoprim-sulfamethoxazole were less active overall, especially against penicillin-intermediate and--resistant strains. Trovafloxacin inhibited all strains at a concentration of < or = 0.25 micrograms/ml and was 8- to 16-fold more potent than ofloxacin or ciprofloxacin.

Influenza vaccination following liver transplantation in children.

Our objective was to determine the immunologic response to two influenza vaccine doses in 39 children who had undergone liver transplantation. Patients received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Sera were collected 4 weeks after each dose and analyzed by a hemagglutination inhibition assay (HAI) for evidence of antibody response to the antigens A/Taiwan/1/86 (H1N1), A/Beijing/32/92 (H3N2), and B/Panama/45/95. Patients with HAI titers of 1:40 or greater were considered to have protective titers. Twenty-six (67%) patients showed a 1:40 or greater titer response to A/Beijing/32/92 1 month after the first vaccination. Only two additional patients were found to have similar titers after the second dose. A higher proportion of patients with protective titers were on smaller amounts of prednisone for body weight or alternate day low dose (< 10 mg/day) prednisone compared to patients on daily low dose or daily high dose prednisone. Patients with protective titers were significantly older (9.0 +/- 2.8 years) than those without protective titers (4.2 +/- 3.4 years, p = .002) following the first inoculation of the A/Beijing/32/92 vaccine component. Similar results were found for the second vaccination and with the H1N1 antigen. Cyclosporine level, gender, and body mass index were not associated with any outcome measures. We conclude that most liver transplant recipients had a protective antibody titer after a single influenza inoculation, but little further advantage was gained after an additional dose. Vaccination of household contacts of younger patients and those patients on daily prednisone or patient chemoprophylaxis may offer greater benefit in prevention of influenza in liver transplant recipients than multiple vaccine doses with current vaccine preparations.

Colonization with penicillin-nonsusceptible Streptococcus pneumoniae in urban and rural child-care centers.

OBJECTIVES: To determine the prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (NS-SP) at 12 child-care centers (CCC) in urban and rural Nebraska and to evaluate the genetic diversity of pneumococcal strains present in the CCC environment. METHODS: Nasopharyngeal cultures for S. pneumoniae were obtained from children 2 to 24 months old. Capsular serotyping, pulsed field gel electrophoresis (PFGE) and microbroth dilution MICs were performed for all S. pneumoniae. Antibiotic exposure was also evaluated as a potential risk factor for colonization with NS-SP. RESULTS: Nasopharyngeal colonization with S. pneumoniae was present in 121 (56%) of 215 children. The MICs of penicillin were 0.12 to 1.0 microgram/ml for 57 (47%) and > 1.0 microgram/ml for 10 (8%) isolates. Clindamycin MICs of > 0.5 microgram/ml were found in 6 isolates (5%). MICs of ceftriaxone were 0.5 microgram/ml in 28% of S. pneumoniae and 1.0 microgram/ml in 7%. PFGE and capsular serotyping demonstrated multiple strains that were penicillin-nonsusceptible in both the urban and rural CCC. PFGE and capsular serotype defined shared strains within each CCC, but some PFGE "types" could be found in multiple serotypes. Antibiotic exposure during the 2 months before nasopharyngeal culture was not a statistically significant risk factor for nasopharyngeal colonization with NS-SP. CONCLUSIONS: NS-SP are highly prevalent in urban and rural Nebraska. PFGE similarities between serotypes may reflect "serotype switching" but may also reflect genetic similarity between S. pneumoniae strains.