Changing the Ecology of Pneumococci with Antibiotics and Vaccines

Ron Dagan; Marc Lipsitch

doi:10.1128/9781555816537.ch18

Chapter 18 : Changing the Ecology of Pneumococci with Antibiotics and Vaccines

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Affiliations: 1: Pediatric Infectious Disease Unit, Soroka University Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 151, Beer-Sheva 84101, Israel; 2: Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115

Content Type: Monograph

Publication Year: 2004

Category: Bacterial Pathogenesis; Clinical Microbiology

Book DOI: 10.1128/9781555816537

Chapter DOI: 10.1128/9781555816537.ch18

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Abstract:

This chapter describes the mechanisms and consequences for the pneumococcal population of the selective pressures imposed by antibiotics and vaccines. While inhibiting pneumococci can have effects on other species of upper respiratory tract (URT) bacteria, the chapter focuses on the selective effects of vaccines and antibiotics on pneumococci. The direct effects of antibiotics on S. pneumonia in the nasopharynx of the treated patient depend on the pharmacokinetics and pharmacodynamics of the agent. Streptococcus pneumoniae resistance to the beta-lactam antibiotic class evolved mainly by complex restructuring of the targets of the beta-lactams, the penicillin-binding proteins (PBPs). To summarize the effect of antibiotics on S. pneumoniae ecology, it is clear that antibiotic treatment in any community profoundly affects S. pneumoniae ecology. Furthermore, a significant reduction of carriage of antibiotic-resistant and multidrug resistant (MDR) S. pneumoniae in the younger siblings of the day care attendees as the result of vaccination of their older siblings was observed. The chapter emphasizes the effects of vaccines and antibiotics on the ecology of pneumococci taking place against a background of a genetically diverse population structured by direct and indirect ecological interactions between strains. The importance of understanding pneumococcal population structure has been appreciated since the earliest days. This understanding can be extended to reconcile the disparate results of clinical trials of antibiotics and vaccines, to evaluate the relative selective effect of different antibiotics for resistant strains, and to project the effects of vaccines and antibiotics on future patterns in the prevalence of serotypes and resistant strains.

Citation: Dagan R, Lipsitch M. 2004. Changing the Ecology of Pneumococci with Antibiotics and Vaccines, p 283-313. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch18

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Changing the Ecology of Pneumococci with Antibiotics and Vaccines

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FIGURE 1

Effect of treatment with various macrolides on the carriage of macrolide-resistant microorganisms in the throat 1 to 6 weeks after initiation of treatment ( 61 ). All children were treated for 7 days (except the azithromycin group, which was treated for 3 days). The median age of the children was 4.2 years, without a significant difference in age distribution between the group. P < 0.005 for azithromycin versus all other groups.

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FIGURE 1

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FIGURE 2

Nasopharyngeal carriage of TS-resistant and penicillin-nonsusceptible S. pneumoniae in children with acute otitis media treated with TS for 10 days (Dagan et al., 39th ICAAC, abstr. 1028). *, P = 0.038 day 1 versus all other days combined. **, P = 0.1 day 1 versus all other days combined.

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FIGURE 2

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FIGURE 3

Nasopharyngeal carriage of macrolide-resistant or MDR S. pneumoniaein children with acute otitis media treated with azithromycin for 5 days (Dagan et al., 43rd ICAAC, abstr. G-1856). *, P < 0.05 compared to day 1. **, P = 0.095 compared to day 1.

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FIGURE 3

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FIGURE 4

Nasopharyngeal carriage of macrolide-resistant and MDR S. pneumoniaein children with acute otitis media treated with azithromycin for 5 days in two periods: 1998 and 2001 to 2002 (Dagan et al., 43rd ICAAC, abstr. G-898). (A) Comparison of the effect of azithromycin on carriage of macrolide-resistant and MDR S. pneumoniae between 1998 and 2001 to 2002; (B) relation of macrolide resistance and MDR in S. pneumoniae isolated from middle ear fluid (MEF) in southern Israel in 1998 (n = 563), 2001 (n = 672), and 2002 (n = 639) (unpublished data).

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FIGURE 4

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FIGURE 5

S. pneumoniae nasopharyngeal carriage in children treated with high-dose amoxicillin-clavulanate for 10 days versus 5 days of azithromycin for acute otitis media, by susceptibility to penicillin, susceptibility to erythromycin, and MDR. Pen, penicillin; ERY, erythromycin; hA/C, high-dose amoxicillin-clavulanate; AZI, azithromycin; D, day; S, susceptible; R, resistant.

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FIGURE 5

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FIGURE 6

Effect of PnCRM7 ( 39 ) and PnOMPC7 ( 65 ) in prevention of acute otitis media caused by VT S. pneumoniae, VT-related S. pneumoniae, non-VT S. pneumoniae, H. influenzae, and M. catarrhalis. Positive values represent a reduction in episodes; negative values represent an increase in cases.

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FIGURE 6

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FIGURE 7

Number of pneumococcal acute otitis media episodes caused by VT (PNCV) and non-VT S. pneumoniae at the Children's Hospital of Pittsburgh from 1 January 1999 to 31 December 2002 (McEllistrem et al., 43rd ICAAC, abstr. G-2047). The arrow indicates the start of widespread vaccination with PnCRM7 in the United States.

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FIGURE 7

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FIGURE 8

Distribution of VT (serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F), serotype 6A, non-VT pneumococci (all other serotypes), and no growth in 149 cultures from 23 younger siblings of day care center (DCC) attendees receiving PnCRM9 and 157 cultures from 23 younger siblings of the control group. This was compared with 1,886 cultures from the 132 older DCC attendee recipients of the PnCRM9 vaccine and 1,862 cultures from 130 DCC attendees receiving control vaccines.

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FIGURE 8

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FIGURE 9

National trends in antibiotic-resistant invasive pneumococcal disease in the conjugate-vaccine era in the United States after the introduction of PnCRM7 to infants and toddlers in 2000 (Kyaw et al., 43rd ICAAC, abstr. G-2045). The reduction figures are for comparison of 2002 to 1999. (A) Penicillin, macrolide, and penicillin plus macrolide nonsusceptibility in children 2 years of age; (B) penicillin nonsusceptibility in children aged 2 to 4 years and adults aged 20 to 39 years and ≥65 years. Pen, penicillin; Macro, macrolides; NS, nonsusceptible.

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FIGURE 9

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Tables

Changing the Ecology of Pneumococci with Antibiotics and Vaccines

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TABLE 1

Observation studies of the association between antibiotic used and carriage of antibiotic-nonsusceptible S. pneumoniae a

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10.1128/9781555816537/tab18-1.gif

TABLE 1

Observation studies of the association between antibiotic used and carriage of antibiotic-nonsusceptible S. pneumoniae a

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TABLE 2

Prospective studies of the effect of antibiotics on carriage of antibiotic-resistant S. pneumoniae comparing carriage before treatment to carriage during and immediately after treatment a

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10.1128/9781555816537/tab18-2.gif

TABLE 2

Prospective studies of the effect of antibiotics on carriage of antibiotic-resistant S. pneumoniae comparing carriage before treatment to carriage during and immediately after treatment a

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TABLE 3

Studies on the effect of conjugate pneumococcal vaccine on carriage of S. pneumoniae and antibiotic-resistant S. pneumoniae

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10.1128/9781555816537/tab18-3.gif

TABLE 3

Studies on the effect of conjugate pneumococcal vaccine on carriage of S. pneumoniae and antibiotic-resistant S. pneumoniae