Galia Barkai

Seasonality of Antibiotic-Resistant Streptococcus pneumoniae That Causes Acute Otitis Media: A Clue for an Antibiotic-Restriction Policy?

BACKGROUND It is unclear whether reducing antibiotic prescriptions can reduce rates of resistance once resistance becomes prevalent. We attempted to determine whether reduced antibiotic consumption, which is observed yearly in children during the warm season, is associated with a reduction in antibiotic resistance in pneumococcal acute otitis media (AOM). METHODS Antibiotic prescriptions and resistance were measured prospectively during 1999-2003 in 2 demographically distinct populations: Jewish and Bedouin children (aged <5 years) in southern Israel. Associations were assessed using seasonally clustered logistic regression models. RESULTS The study included 236,466 prescriptions and 3609 pneumococcal isolates. Prescription rates decreased during the warm months by 36% and 15% in Jewish and Bedouin children, respectively (P < .001 for the season). Among Jewish children, higher resistance rates were observed during the cold than the warm months (P < .001 for each antibiotic). This difference remained significant after adjustment for age, ethnic group, study year, history of antibiotic use, and serotype. The difference was not observed in Bedouin children. CONCLUSIONS Rapid seasonal decline in resistant AOM-causing pneumococci occurred only in Jewish children, among whom a marked prescribing seasonality was noted, and not in Bedouin children, among whom prescription was less seasonal. The rapid seasonal decrease in resistance associated with markedly reduced antibiotic use suggests that drug-resistant pneumococci may pay a fitness cost.

Community prescribing and resistant Streptococcus pneumoniae.

We investigated the association between prescribing antimicrobial agents and antimicrobial resistance of Streptococcus pneumoniae among children with acute otitis media in southern Israel. During a 6-year period, all prescriptions of a sample of ≈20% of Jewish and Bedouin children <5 years of age were recorded and all pneumococcal isolates from middle ear fluid were collected. Although antimicrobial drug use was significantly higher in Bedouin children, the proportion of S. pneumoniae isolates with penicillin MIC ≥1.0 μg/mL was significantly higher in Jewish children. In both populations, antimicrobial prescriptions were markedly reduced over time, especially for penicillins and erythromycin. In contrast, azithromycin prescriptions increased from 1998 to 2001 with a parallel increase in macrolide and multidrug resistance. Penicillin resistance was associated with macrolide resistance. These findings strongly suggest that azithromycin affects increased antimicrobial resistance, including multidrug resistance, in S. pneumoniae.

Four antibiotic-resistant Streptococcus pneumoniae clones unrelated to the pneumococcal conjugate vaccine serotypes, including 2 new serotypes, causing acute otitis media in southern Israel.

This study examined the prevalence of antibiotic-resistant clones that belong to serotypes not included in the pneumococcal conjugate vaccines and that cause a significant percentage of acute otitis media (AOM) in children in southern Israel. During 1998-2001, 2467 pneumococcal isolates, obtained from middle-ear fluid of children <3 years old with AOM, were characterized by antimicrobial susceptibility testing, serotype testing, and pulsed-field gel electrophoresis. Non-vaccine type (NVT) strains constituted 477 (19%) of the 2467 isolates, of which 173 (36%) belonged to only 4 serotypes: 35B, 33F, 21, and 15B/C. For serotype 35B, 47 (96%) of 49 strains were penicillin nonsusceptible, and 93% constituted a single clone; for serotype 33F, 31 (82%) of 38 strains were penicillin nonsusceptible, and 95% constituted a single clone; for serotype 21, 38 (93%) of 41 strains were penicillin nonsusceptible, and 93% constituted a single clone; for serotype 15B/C, 22 (49%) of 45 strains were penicillin nonsusceptible, and 42% constituted a single clone. Two of these clones have not been described elsewhere. The high prevalence of NVT clones should increase the awareness of the potential for replacement of the vaccine strains with these NVT antibiotic-resistant strains.

Salmonella diskitis in a 2-year old immunocompetent child.

Spine infections are uncommon in paediatrics and are generally caused by Staphylococcus aureus. Salmonella spp. are a rare cause of spine infections, usually affecting children with sickle-cell anaemia. We present a case of group C1 Salmonella diskitis in a previously healthy 2-y-old child, and review the relevant literature.

Potential contribution by nontypable Haemophilus influenzae in protracted and recurrent acute otitis media.

Background: Characterization of acute otitis media (AOM) caused by nontypable Haemophilus influenzae (NTHi) is important, particularly in view of the efforts to develop vaccines against NTHi. To characterize NTHi AOM a large database of culture-positive AOM cases was analyzed. Methods: All culture-positive AOM episodes (NTHi, Streptococcus pneumoniae, Moraxella catarrhalis, and Streptococcus pyogenes) in children <5 years old from 1999 through 2006, processed in our center were included. One isolate was counted per episode (≤30 days). Demographic and clinical data were retrieved from charts or by telephone interviews. Multivariable regression analysis models were used. Results: Twelve thousand eight hundred twenty-three (8145 culture-positive) episodes were included. NTHi was recovered in 4928 episodes; S. pneumoniae in 4399 episodes, M. catarrhalis in 499, and S. pyogenes in 447 episodes. Independent risk factors for NTHi AOM (in culture-positive episodes) were: winter (odds ratio [OR]: 1.2, 95% confidence interval [CI]: 1.05–1.33, P = 0.006); bilateral AOM (OR: 1.26, 95% CI: 1.12–1.42, P < 0.001); >3 previous AOM episodes (OR: 1.27, 95% CI: 1.11–1.47, P = 0.001); and antibiotic consumption in previous month (OR: 1.3, 95% CI: 1.15–1.46, P < 0.001). ORs for these variables remained significant when the analysis was conducted on single-pathogen AOM only. For both NTHi and S. pneumoniae, risk factors for mixed episodes were older age and bilateral AOM. Conclusion: NTHi AOM is characterized by higher occurrence in winter, bilaterality, recurrence, and previous antibiotic treatment compared with that caused by S. pneumoniae. These findings are in agreement with data associating NTHi with protracted or recurrent morbidity. The finding that S. pneumoniae and NTHi mixed episodes are more likely to occur in older children and in bilateral AOM suggests that interaction between these 2 pathogens contributes to chronicity or complexity of AOM.

Will reduction of antibiotic use reduce antibiotic resistance? : The pneumococcus paradigm

Community-acquired respiratory infections in general, and those caused by S. pneumoniae in particular, are the main reason for prescribing antimicrobials in young children. Antibiotic drug abuse is common. This is the basis for the initiative for the reduction in antibiotic use. However, failure to consider that not all antibiotics are similar in their effect on promotion of resistance has led to continuous emerging resistance. In the present article, the trends in prescribing antibiotics in young children and their interrelation with antibiotic resistance among clinical respiratory isolates of S. pneumoniae in children will be reviewed, along with theoretical considerations and research evidence that led to concluding that among antibiotics, the least resistance-promoting drug for S. pneumoniae is amoxicillin (+/− clavulanate), whereas oral cephalosporins and azithromycin demonstrate a higher resistance-promotion potential in the individual population in the community. Although antibiotics differ in their resistant-promotion potential, all still do promote resistance.

The effect of universal toddlers-only hepatitis A virus vaccination program on seropositivity rate in unvaccinated toddlers: evidence for reduced virus circulation in the community.

Background: In July 1999, a national toddler-only hepatitis A virus (HAV) vaccination program was introduced in Israel. Passive and active surveillance showed a large reduction in disease rate, but an objective measurement was needed. We hypothesized that toddlers vaccination in a population living in an endemic area would reduce virus circulation, resulting in reduced HAV seropositivity rates in unvaccinated toddlers. Methods: The study was conducted among Bedouin children in southern Israel, for whom HAV vaccine coverage reached 85.5% and 74.9% for first and second HAV vaccine doses, respectively, in 2000. Toddlers received 2 doses of HAV vaccine at 18 and 24 months. Data on vaccine coverage was received from well-baby clinics. Sera were obtained from healthy unvaccinated 16- to 20-month-old toddlers. Anti-HAV immunoglobulin (Ig)G concentrations were tested by enzyme-linked immunosorbent assay. Results: A total of 629 sera were tested (209 obtained in 1991–2000 and 420 obtained in 2001–2002). Seropositivity rates of ≥100 mIU/mL ranged from 16.2% to 19.6% in 1991 through 2000 (children born before immunization program). These rates dropped to 2% in 2001–2002 and to 0% in 2003 through 2007. Furthermore, IgG concentrations were significantly lower (P < 0.001) in samples taken in 2000, only a few months after beginning of vaccination, than in those taken before initiation of the HAV immunization program (1991–1998), suggesting a marked reduction in circulating HAV resulting in natural boosting. Conclusions: Because HAV vaccines are licensed in children ≥12 months old, rates of anti-HAV seropositivity in unvaccinated toddlers can be an objective and sensitive tool to evaluate the effect of immunization program on virus circulation. This method is of special value in communities where no appropriate surveillance is in place.