Intrinsic epidemicity of Streptococcus pneumoniae depends on strain serotype and antibiotic susceptibility pattern.

Streptococcus pneumoniae is a major cause of invasive diseases worldwide. It spreads through an interindividual transmission, followed by usually harmless colonization of the host. Possible transmission differences reflecting intrinsic strain features (e.g., serotype and antibiotic susceptibility) have been little studied so far. In this study, we used epidemiological data from an interventional trial of S. pneumoniae carriage among kindergartners and developed a mathematical model to estimate the transmission parameters of the different strains isolated during that study. We found small but significant transmissibility differences between the observed serotypes: serotypes 3, 6A, and 19A were found to be the most epidemic, while serotypes 23F, 9V, and 14 were the least epidemic. Further analysis indicated that, within a serotype, susceptible and resistant strains had different abilities to be transmitted. Susceptible-to-resistant transmission rate ratios were computed for five serotypes; susceptible strains were significantly more epidemic than resistant strains for serotypes 6A (mean, 1.02) and 19F (1.05). Serotype 19A resistant strains were not outcompeted by susceptible strains (0.97). Nonsignificant trends were observed for serotypes 6B (1.01) and 15A (0.98). Our results support the existence of heterogeneous abilities of the different serotypes for host-to-host transmission. They also suggest that antibiotic susceptibility within a serotype affects this transmissibility. We conclude that pneumococcal strains should not be considered equally at-risk in terms of transmission. Further quantification of strain-specific epidemic potential is needed, especially in a context of extensive use of conjugate vaccines with the aim of preventing pneumococcal infections.

Reduction of antibiotic use in the community reduces the rate of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae.

BACKGROUND: There is a lack of evidence documenting the impact of optimized antibiotic use on the rates of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae (PNSP) in children. This study evaluates the effect of community-based intervention strategies on the prevalence of pnsp colonization. METHODS: A controlled, population-based pharmacoepidemiological trial was conducted from January through May 2000. Three French geographic areas were selected on the basis of demographic similarities. Two intervention strategies were implemented: (1) reduced antibiotic use, which was achieved by not prescribing antibiotics for presumed viral respiratory tract infections (the prescription-reduction group); and (2) better adaptation of dose and duration (the dose/duration group). A control group received no intervention. The target population was children aged 3-6 years who were attending kindergarten. Oropharyngeal pneumococcus colonization and antibiotic use were monitored throughout the 5-month study. RESULTS: The prescription-reduction, dose/duration, and control groups included 601, 483, and 405 children, respectively. The interventions induced significantly larger decreases in antibiotic use in the prescription-reduction group (-18.8%) and dose/duration group (-17.1%) than in the control group (-3.8%), and the rates of PNSP colonization were initially similar for the 3 groups (52.5%, 55.1%, and 50.0%, respectively). At the end of the 5-month study, the rates of PNSP colonization were 34.5% for the prescription-reduction group (P=.05) and 44.3% for the dose/duration group (P=.8), compared with 46.2% for the control group. CONCLUSIONS: Intensive educational strategies aimed at optimizing antibiotic use can significantly reduce the rate of PNSP colonization in areas with high resistance rates.

Narrow versus broad spectrum antibacterials: factors in the selection of pneumococcal resistance to beta-lactams.

Streptococus pneumoniae represents an interesting model to discuss the relative impact of broad versus narrow spectrum antibacterials as potential selectors for resistance. Indeed, this pathogen is responsible for potentially severe infections in the community, and has a great capacity for acquisition of resistance to antibacterial agents. It has been the focus of many studies to elucidate some unique aspects of molecular biology, including the adaptive mechanisms responsible for emergence and spread of multiresistance. In the past, the use of narrow spectrum agents was recommended in order to try to reduce the risk of selection of resistance. This concept is nowadays somewhat obsolete for several reasons. S. pneumoniae is able to acquire resistance to antibacterials belonging to different families of drugs through different molecular mechanisms. Thus, selection of multiresistant pneumococci can result from exposure to very different agents, including narrow spectrum as well as broad spectrum agents. In vitro studies have shown a different potential for selection of resistance among the beta-lactam agents. Furthermore, several studies have more or less directly established a close relationship between the level of antibacterial use and the rate of selection of resistance. In addition to the overall amount of antibacterials prescribed in the community, several other factors have been shown to influence the rate of selection of resistance, including the use of doses that are too low, the length of therapy and the duration of bacterial exposure to long-acting agents compared to drugs with short half-lives. Therefore, there are three main ways to control selection and spread of resistant strains: by (i) reducing the amount of antibacterials used; (ii) using optimal dosages (avoiding underdosing) and treatments of short duration; and (iii) reducing the risk of transmission among young children attending daycare centres or kindergartens. In order to help physicians reduce the number of unnecessary prescriptions, it is important to develop rapid tests to recognise the bacterial origin of a febrile illness and even more important to detect resistance to antibacterials. However, apart from rapid diagnostic tests for streptococcal pharyngitis, those tests are not currently available. As a consequence, currently, the debate around narrow versus broad spectrum antibacterials remains a false debate. Physicians should use broad spectrum agents in many instances of upper or lower respiratory tract infection, taking into consideration the probable pathogens and the risk of (multi)resistance to antibacterials. Once rapid diagnostic are available in community practice, allowing a precise diagnosis of the offending agent and its susceptibility profile, physicians will be able to add to their current criteria the selective potential for resistance of the antibacterials that appear to be active in vitro.

Moving from recommendation to implementation and audit: part 1. Current recommendations and programs: a critical commentary.

Growing concern over the spread of resistance to antibiotics and other antimicrobials has prompted a plethora of recommendations for its control. Strategic programs for resistance containment have been initiated in various countries, particularly in Western Europe and North America. The World Health Organization and the European Union have responded to the need for international action by publishing guidance and encouraging collaboration. These recommendations rightly focus on controlling resistance in the community. They agree on the importance of surveillance of resistance patterns and antibiotic usage and the need to encourage judicious antibiotic usage (especially through education of prescribers and the public). Yet there remains a pressing need for the implementation of effective actions to address these issues. Important considerations given less attention include infection prevention (e.g. through immunization), the use of rapid diagnostic tests to reduce antibiotic usage, audit of implemented actions, and the provision of feedback. Furthermore, research is necessary to fill the substantial gaps in our knowledge. Notably, the reversibility or containment of resistance with the optimization of antibiotic usage has yet to be definitely established. For now, antimicrobial management programs should focus on ensuring the most appropriate use of antimicrobials rather than simply on limiting choices. Finally, developed countries must recognize that a truly global approach to resistance containment will require greater support for developing countries.

Antibiotics for nasopharyngitis are associated with a lower risk of office-based physician visit for acute otitis media within 14 days for 3- to 6-year-old children.

OBJECTIVES: This study was designed to analyse factors potentially influencing children's return visits to physicians for symptoms of acute otitis media (AOM) within 14 days after being diagnosed with nasopharyngitis (NP), and the impact of recent antibiotic use. DESIGN: A controlled population-based pharmaco-epidemiological trial in 3- to 6-year-old children conducted from January to May 2000. SETTING: Three different geographical regions in France. PARTICIPANTS: Among 2507 eligible children, 2456 could be analysed and 505 children had 634 office-based physician visits (OBPV) for NP symptoms. INTERVENTIONS: The statistical associations between antibiotics prescribed for NP and an OBPV for AOM within 14 days in a population-based study were analysed along with risk factors of AOM. MAIN OUTCOMES MEASURE: Clinical events and antibiotic use. RESULTS: During the 2 weeks following physician-diagnosed NP, antibiotic use, especially a beta-lactam, significantly decreased the risk of OBPV for AOM in children (odds ratio=0.2; 95% confidence interval=0.09-0.7; P=0.002). CONCLUSION: Antibiotics prescribed to children for NP seem to protect during the following 2 weeks against the risk of OBPV for AOM. It remains to be determined whether a subgroup at high risk of developing AOM after a viral infection exists and what might be the best strategy to adopt for NP in a national programme of optimal antibiotic use.

Early bacterial and inflammatory responses to antibiotic therapy in a model of polymicrobial peritonitis in rats.

OBJECTIVE: To assess the consequences of different more or less selective treatments on the microbiological and inflammatory responses within the peritoneum. METHODS: The early effects of various antibiotic regimens were evaluated in a model of polymicrobial peritonitis with specifically prepared organisms. Six regimens (amoxycillin plus gentamicin, pefloxacin, ornidazole, pefloxacin plus ornidazole, imipenem and imipenem plus gentamicin) were evaluated at 24 h and 3 days in a non-fatal model of peritonitis in rats achieved by implantation of a capsule containing Escherichia coli, Bacteroides fragilis and Enterococcus faecalis. RESULTS: Therapies that disregarded several organisms were associated with persistence of the strains and an increased peritoneal inflammatory response within the peritoneum. In contrast, therapies active against Enterobacteriaceae and anaerobes were associated with decreases of all the inoculated organisms and a smaller inflammatory response. CONCLUSION: Therapies that disregarded the microorganisms implicated in peritoneal infection are associated with delayed bacterial eradication. The persistence of these organisms within the peritoneal fluid might be involved in prolonged peritoneal inflammation. Although it disregards enterococci, the standard therapy, represented by therapy against Enterobacteriaceae and anaerobes, demonstrates satisfactory effects towards all the inoculated organisms. This apparent contradiction could be related to mechanisms of bacterial synergy.

Transfusion-related infectious mononucleosis.

Careful donor selection has reduced but not eliminated the risk of transfusion-transmitted infections. We report a case of transfusion-related infectious mononucleosis. Given the pivotal role of Epstein-Barr virus in the development of lymphoproliferative disorders after solid-organ transplantation, its potential transmission by blood products deserves to be considered in this population.

Evaluation of the effect of interleukin-10 on the multiplication of Mycobacterium avium complex in human macrophages and in C57BL/6 mice.

OBJECTIVE: To examine the effect of recombinant human IL-10 (rhIL-10) on MAC infection of human macrophages and C57BL/6 mice. METHODS: We compared rhIL-10 with the effects of the immunosuppressive drugs prednisolone and cyclosporin A, both in vitro and in vivo. RESULTS: There was no effect of rhIL-10 on the multiplication of MAC in human macrophages after 1 week of infection. In C57BL/6 mice, rhIL-10 at 2.5 or 25 m g/mouse had no additional multiplicatory effect after 3 weeks of infection, while the spleens of mice treated with prednisolone had 600% higher bacteria than controls or rhIL-10-treated mice (p0.01). CONCLUSIONS: These data suggest that rhIL-10 does not further decrease the resistance of human macrophages and C57BL/6 mice to MAC infection, whereas prednisolone leads to increased multiplication of MAC in the spleens of infected C57BL/6 mice. These results may be of interest in the context of the therapeutic use of rhIL-10 in some autoimmune disorders.

Role of the quorum-sensing system in experimental pneumonia due to Pseudomonas aeruginosa in rats.

The virulence of Pseudomonas aeruginosa is partly controlled by the las quorum-sensing system. A rat model of acute pneumonia was used to investigate the pathophysiological impact of this system by comparing the virulence of the wild-type virulent laboratory strain PAO1 with that of its lasR-deleted mutant PAOR. In comparison with PAO1, PAOR was avirulent after an instillation of 106 cfu (mortality rates, 72 versus 0%, respectively; p < 0.0001). A ten-fold higher inoculum slightly increased the mortality rate induced by PAOR (25%), which remained lower than that induced by PAO1 (75%, p = 0.0001). In addition, with both inocula lung and bronchoalveolar lavage bacterial counts were significantly lower in rats infected with PAOR than with PAO1 (p

Amoxicillin-clavulanate therapy increases childhood nasal colonization by methicillin-susceptible Staphylococcus aureus strains producing high levels of penicillinase.

We examined factors associated with penicillinase production by nasal carriage Staphylococcus aureus strains in 648 children aged 3 to 6 years attending 20 randomly sampled playschools. The children were prospectively monitored for drug use and medical events for 6 months and were then screened for S. aureus carriage. Isolates were tested for their susceptibility to penicillin G and methicillin, and penicillinase production by methicillin-susceptible, penicillin-resistant strains was quantified. S. aureus was isolated from 166 children (25.6%). Exposure to amoxicillin-clavulanate during the previous 3 months was associated with higher penicillinase production by penicillin-resistant, methicillin-susceptible strains (odds ratio, 3.6; P = 0.03). These results suggest that use of the amoxicillin-clavulanate combination could induce a herd selection process of S. aureus strains producing higher levels of penicillinase.