CLINICIAN INTERVIEW

                               ACUTE OTITIS MEDIA IN THE ERA OF PCV-7
                                         Interview with Stanley L. Block, Jr, MD, FAAP

     Dr Block is president of Kentucky Pediatric Research            papers, review articles, and abstracts on acute otitis
 and has practiced full-time primary care pediatrics in              media (AOM), vaccines, microbiology, antibiotic resis-
 rural Bardstown, Ky, for the past 22 years. He has been             tance in pediatrics, and attention-deficit/hyperactivity
 board recertified twice and holds appointments as                   disorder. He was first author of landmark papers
 Clinical Professor of Pediatrics at the University of               describing the role of penicillin-resistant pneumococcus
 Louisville and the University of Kentucky.                          in AOM, Chlamydia pneumoniae in AOM, and C
     Dr Block received his Doctor of Medicine degree from            pneumoniae and Mycoplasma pneumoniae in com-
 the University of Kentucky and completed his postgradu-             munity-acquired pneumonia in children. He has pre-
 ate work in pediatrics at Wake Forest University School             sented clinical data at annual meetings of the American
 of Medicine. For significant contributions to pediatric             Academy of Pediatrics, the Society for Pediatric
 medicine, Dr Block has been awarded the 1998                        Research, and the Interscience Conference on
 Researcher of the Year in Pediatric Private Practice by the         Antimicrobial Agents and Chemotherapy (ICAAC),
 American Academy of Pediatrics; the 2001 Charles                    and at pediatric grand rounds across the United States,
 Bluestone Award by the American Society of Pediatric                Canada, and Europe.
 Otolaryngology; the 2002 and 2003 Burtis Burr Breese                    In the following interview with Advanced Studies in
 Award by the Pediatric Infectious Disease Society; and              Medicine (ASiM), Dr Block discusses what impact
 the 2004 Distinguished Alumnus Award by the                         immunization of the pediatric population with 7-valent
 University of Kentucky Medical School. Kentucky                     pneumococcal conjugate vaccine (PCV-7) will have on
 Pediatric Research is one of the largest pediatric ambula-          AOM.
 tory research groups in the United States, participating
 in more than 250 clinical trials.
     Dr Block is a reviewer for several publications,
 including the Pediatric Infectious Disease Journal,
 Pediatrics, Southern Medical Journal, the Journal of
 Pediatrics, and Pediatric Drugs. He serves as a writer
 and editorial board advisor for the Pediatric Infectious            ASiM: How important are the third dose and the
 Disease Journal, Infectious Diseases in Children,                   booster dose of PCV-7 for full protection against
 and Pediatric Annals, as well as the quarterly Pediatric            vaccine serotypes?
 Infections Forum. He is the co-chief editor for and an                 Dr Block: The first 3 doses of PCV-7 have a major
 advisory board member of the National Campaign for                  impact on invasive disease. For most children, the
 Influenza Prevention and an advisory board member of                peak occurrence of AOM is between 6 and 18 to 24
 the National Alliance for Advancement of ADHD                       months of age.1,2 Consequently, optimizing protec-
 Care.                                                               tion against mucosal disease such as AOM after 12
     Dr Block is a recognized opinion leader on infectious           months is very important. Prelicensure evaluation of
 diseases in ambulatory pediatrics, having published, as             PCV-7 in 37 868 infants within Kaiser Permanente
 first author or co-author, more than 130 original                   found that more than 97% of recipients of PCV-7

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                                                    CLINICIAN INTERVIEW

achieved 0.15 mg/mL or greater anticapsular anti-                  ASiM: Has the influence of “herd immunity” in
body for all serotypes after the primary series of 3               your study exceeded previous predictions of protec-
doses, which correlates with the observed protective               tion of AOM?
efficacy for invasive disease of 97.3%. The children                   Dr Block: Herd immunity is the indirect protection
were randomized by a ratio of 1:1 to receive PCV-7                 from infection of susceptible members of a population
or control vaccine at 2, 4, 6, and 12 to 15 months                 brought about by the presence of immune individuals.
of age.3                                                           Along with the profound shift in AOM microbiology
    However, the data for children who received the                with the advent of PCV-7, we have also seen a much
third dose late or not at all suggest that protection              greater impact on overall AOM rates than the modest
against mucosal disease did not last to 12 months of               6% to 9% drop suggested by premarket studies. Before
age without the third dose.4 Additionally, PCV-7 was               PCV-7, we did about 100 to 125 ear taps a year for kids
most effective shortly after the booster dose (ie, during          with more than 2 treatment failures. Now it is 25 to 35,
ages 15 to 18 months) when vaccinated children had                 tops. We are just not seeing severe AOM anymore.
12.2% fewer otitis visits than control children (95%                   I attribute this impact largely to herd immunity,
confidence interval, 8.2 to 16.0).4 Thus, the available            which explains why it was not seen in earlier studies.
immunologic data suggests that the booster dose after              They were done in small segments of their respective
12 months of age is an important facet of protection               populations, in contrast to our community where
against mucosal disease,4 whereas 2 or 3 doses are                 almost all children have been vaccinated.
probably sufficient to protect most children against                   So, we have seen notable herd immunity occurring
invasive disease.5                                                 on rates of AOM and sinusitis in the relatively closed
                                                                   population within our area when rates of uptake and
ASiM: Your participation in multiple clinical trials               availability of PCV-7 are high.
of PCV-7 has enabled you to immunize 94% of                            Some critics say these findings are the result of the
your pediatric patients with PCV-7 since 2000.                     more stringent diagnostic criteria for pediatric AOM
What changes in the rate of upper respiratory tract                and acute bacterial rhinosinusitis (ABRS) that have
infections have you seen in your pediatric popula-                 been developed and propagated by public health offi-
tion now that the majority has received at least 2 to              cials over the past decade. Yet, these criteria likely had
3 doses of PCV-7?                                                  no impact on our results. All of the pediatricians were
    Dr Block: We have seen an impact far exceeding                 experienced otoscopists who have performed tympa-
previous expectations of PCV-7 on rates of both                    nocentesis for routine care and clinical research,7 and
AOM and sinusitis, and also on the number of total                 our clinicians were already using defined parameters
antibiotic days. We compared annual rates of AOM,                  confirmed by clinical examination. Our diagnostic
sinusitis, and antibiotic use during the first 3 years of          accuracy for AOM has been corroborated in multiple
life in a cohort of 274 children consecutively born                clinical trials using tympanometry, acoustic reflectom-
from 1993 through 1994 (pre–PCV-7) with a cohort                   etry, and/or especially tympanocentesis. Indeed, our
of 221 children consecutively born from 2000                       diagnostic criteria for pediatric AOM and ABRS have
through 2001, 94% of whom received 3 or 4 doses of                 remained consistent for the last 12 years. Therefore,
PCV-7.6 Both cohorts of children were 91% white,                   the changes in rates of infection that we observed were
and nearly half were enrolled in day care. The mean                strictly related to the introduction of PCV-7. But this
number of AOM episodes during the first 3 years of                 also means that for practices using poor examination
life was reduced by 19% in the PCV-7 cohort com-                   technique, looser diagnostic criteria, looser prescrip-
pared with the pre–PCV-7 cohort. Surprisingly, the                 tive pens, or disposable speculums and otoscopes with
biggest impact was actually in year 3, when there was              alkaline batteries, the reduction on rates of AOM and
a 29% reduction.6                                                  sinusitis likely will be much less perceptible.
    With regard to rates of sinusitis, there was an
impressive 59% reduction (range 39%-69% annually)                  ASiM: With regard to the etiology of AOM, have
in the first 3 years of life in the PCV-7 cohort com-              you seen changes in the rates of recovery of the pre-
pared with the pre–PCV-7 cohort (Block SL, unpub-                  dominant pathogens?
lished data, 2004).                                                   Dr Block: I think a historical perspective will help

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                                                     CLINICIAN INTERVIEW

 us understand this issue. Approximately 20 000 cases               H influenzae. So, I surmise that these microbiologic
 of invasive Haemophilus influenzae occurred in the                 changes are probably occurring across the United States.8
 United States in the early 1980s. In 1985, the first H
 influenzae type B (Hib) vaccine was introduced fol-                ASiM: What are the implications of the changing
 lowed by a conjugate Hib vaccine in 1987. The wide-                microbiology for future treatment of AOM as
 spread use of these vaccines has resulted in a greater             young children approach universal rates of PCV-7
 than 99% decline in invasive disease compared with                 vaccination with at least 3 doses?
 the early 1980s.                                                       Dr Block: Once the vaccine supply is adequate, I
     This dramatic decline in invasive H influenzae dis-            believe we will continue to see a decline in the overall
 ease was an impressive public health benefit but it also           proportion of pneumococcal pathogens in AOM. We
 altered the bacterial etiology of AOM. As H influenzae             are now entering a gram-negative era for AOM. For
 decreased, Streptococcus pneumoniae became the more                coverage of both gram-negative pathogens and the
 prevalent cause of bacterial AOM. Now that a conju-                residual penicillin-susceptible and intermediately resis-
 gate pneumococcal vaccine has been mandated in chil-               tant pneumococci, the third-generation cephalosporins
 dren, it is not unexpected that the use of PCV-7 has               and amoxicillin/clavulanate demonstrate excellent in
 also had a major impact on the prevalence of the key               vitro susceptibility and in vivo clinical efficacy in chil-
 AOM pathogens.                                                     dren with AOM. Amoxicillin/clavulanate has been
     Among children aged 7 to 24 months with severe                 accepted as the gold standard of treatment by the
 and/or refractory AOM, we compared 336 AOM iso-                    American Academy of Pediatrics/American Academy of
 lates obtained from 1992 to 1998 (pre–PCV-7) with                  Family Physicians (AAP/AAFP).9 It is a very good drug
 83 AOM isolates obtained from 2000 to 2003 from                    for gram-negative pathogens as well as most strains of
 children who had received 3 or 4 doses of PCV-7.2 The              pneumococci. But with the emergence of H influenzae
 rate of gram-negative pathogens increased from 50%                 as the major pathogen in AOM and the increase in
 to 66% (P <.001). Nontypeable H influenzae increased               beta-lactamase–producing organisms, certain third-
 from 41% to 56% (P = .01).2 Among gram-negative                    generation cephalosporins should be included in any
 AOM isolates, the overall rate of beta-lactamase–pro-              armamentarium for the treatment of AOM as these
 ducing organisms increased from 32% to 47%                         agents also have excellent activity and cause less gas-
 (P = .007)2 showing that beta-lactamase–producing                  trointestinal disturbance.
 gram-negative organisms are responsible for about half                 Among the third-generation oral cephalosporins,
 of all middle ear isolates.                                        cefdinir, cefpodoxime, cefixime, and ceftibuten are
     Among PCV-7–vaccinated children who had                        available for the treatment of AOM.10 Of the avail-
 recurrent AOM (defined as an episode of AOM with-                  able third-generation cephalosporins, cefdinir and
 in 7 to 28 days of the last dose of antibiotic), we found          cefpodoxime have a distinct advantage in terms of
 that 72% of cases were due to H influenzae rather than             both intermediate penicillin-nonsusceptible S pneu-
 drug-resistant pneumococcus.2 In fact, the proportion              moniae and gram-negative coverage.11,12 Cefixime
 of pneumococcal pathogens has declined significantly               provides limited pneumococcal coverage.12
 from 48% pre–PCV-7 to 31% post–PCV-7 (P =                          Ceftibuten does not provide coverage of pneumococ-
 .007). We have also seen a moderate decrease in the                cus or Moraxella catarrhalis,13 and therefore should
 rate of penicillin-nonsusceptible pneumococci from                 not be used in pediatric patients for AOM. Despite
 25% to 19%; however, this decrease is not statistically            the coverage it provides, a real limitation of cefpo-
 significant.2                                                      doxime oral suspension is that it receives low ratings
     Casey and Pichichero reported similar findings                 for taste and aftertaste.14 In contrast, cefdinir oral sus-
 among children in Rochester, NY, with recurrent or per-            pension receives high ratings for taste and aftertaste
 sistent AOM (defined as nonresponders after 1 or 2                 when compared with cefpodoxime or cefuroxime.14
 empiric antibiotic courses or failures after 48 hours on           Both cefpodoxime and cefdinir can be administered
 treatment) who had received PCV-7.8 The authors                    once daily for 10 days or twice daily for 5 days.10
 found that 65% of recovered organisms during the peri-             These benefits of better taste and flexible dosing may
 od 2001 to 2003 were gram negative, 57% were                       help to improve patient adherence leading to better
 H influenzae, and 55% were beta-lactamase–positive                 patient outcomes.

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                                                      CLINICIAN INTERVIEW

ASiM: How does the clinical efficacy of standard-                        Our data indicate that cefdinir given twice a day for
dose amoxicillin/clavulanate compare with that of                    5 days was very effective in children who had nonre-
the third-generation cephalosporins in the treat-                    fractory AOM, particularly among PCV-7 recipients.
ment of children with AOM?
    Dr Block: We conducted an investigator-blinded clin-             ASiM: Will high-dose amoxicillin remain an
ical trial comparing 5 days of cefdinir (14 mg/kg) given             appropriate first-line therapy for AOM in children
twice daily versus 10 days of amoxicillin/clavulanate (45            who are fully immunized with PCV-7?
mg/kg of amoxicillin component) given twice daily.15 We                  Dr Block: Although we may want to consider an
used low-dose amoxicillin/clavulanate in this study                  antibiotic that provides better gram-negative coverage
because the high-dose formulation was approved only 2                for initial therapy in children who have received PCV-
to 3 months before we began enrolling patients, and our              7, remember that our data and that from Casey and
study protocol had already undergone laborious revisions             Pichichero were comprised mostly of children with
and approval by institutional review boards. This was a              recurrent or persistent AOM.8 I believe high-dose
nontympanocentesis study that used clinical endpoints,               amoxicillin should still remain first-line therapy for
and the diagnostic criteria for AOM were definitely ade-             AOM. Amoxicillin is fairly inexpensive, extremely
quate. In fact, our diagnostic criteria were more compre-            safe, modestly effective, and will cover a fair amount of
hensive than those in the AAP/AAFP guidelines because                pneumococcus and beta-lactamase–negative strains of
clinical signs/symptoms of otalgia, ear fullness, decreased          H influenzae. The use of this narrower-spectrum drug
hearing, or purulent discharge due to acute perforation of           will help prevent the overuse of the more potent
the tympanic membrane had to be associated with the                  antibiotics in the all-too-often cases of “diagnostic
presence in at least one ear of a minimum of 2 of the fol-           uncertainty,” overdiagnosis, busy practitioners, and
lowing: a bulging tympanic membrane, loss of the nor-                prescriptive pens susceptible to frequent parental pres-
mal light reflex and tympanic membrane landmarks, and                sure. Because the overall clinical efficacy of high-dose
abnormal tympanic membrane mobility. Middle ear effu-                amoxicillin is reasonable and because infections with
sion was corroborated in all patients by acoustic reflec-            H influenzae and M catarrhalis may be less severe and
tometry.15 Based on data from experienced otoscopists                often resolve without treatment,19 at least initially with
using optimal culture technique for tympanocentesis, a               a tympanocentesis, high-dose amoxicillin is still an
pathogen should be present in 87% to 95% of cultures                 appropriate choice.
from an ear meeting these criteria.16-18
    In this particular study, the mean age of the chil-              ASiM: Will the changes in AOM microbiology in
dren was 2.8 (±1.8) years, and 64% had received from                 the PCV-7 era affect treatment choices for children
1 to 4 doses of PCV-7.15 Overall, clinical response rates            who fail an initial course of therapy?
at the end-of-therapy visit (2-4 days post-therapy for                   Dr Block: When one looks at the sum total of the
either regimen) were equivalent between the 2 drugs                  data, it looks like either amoxicillin/clavulanate or cef-
(88% for cefdinir and 85% for amoxicillin/clavu-                     dinir should be the agent of choice when a child fails
lanate).15 However, among the subset of children who                 first-line therapy with amoxicillin. Both drugs have
had ever received PCV-7, there was a statistically sig-              advantages and disadvantages. Amoxicillin/clavulanate
nificant difference in efficacy favoring cefdinir over               probably has slightly better pneumococcal coverage,
amoxicillin/clavulanate (92% vs 82%, P = .024; 95%                   especially for penicillin-resistant pneumococcus.
confidence interval, 1.1 to 18.4).15                                 However, data from our practice and Casey’s suggest
    When we looked specifically at children aged 6 to                that there has been a reduction in high-level resistance
24 months, in whom the occurrence of AOM is great-                   of pneumococci to penicillin since the introduction of
est, the impact of PCV-7 on drug efficacy was even                   PCV-7.5
more profound. Clinical cure rates were 92% for cef-                     Among children 7 to 24 months of age, the choice
dinir compared with 77% for amoxicillin/clavulanate,                 between these agents is probably a flip of the coin.
with a P value of .019 when stratified by age.15 The                 Cefdinir has some real advantages in terms of superior
95% confidence intervals were within 15% (3.5,                       palatability and the fact that it can be administered
26.2), which is somewhat greater than the 10% that                   once daily rather than twice daily for 10 days. These
we would like to see.                                                important benefits may help improve patient adher-

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                                                     CLINICIAN INTERVIEW

 ence thereby improving the chances that a full course              strated between-treatment differences. This study
 of therapy will be completed. Yet, for the clinician               showed a statistically significant difference between
 who sees patients daily, the AAP/AAFP guidelines                   amoxicillin/clavulanate and cefdinir in children who
 indicate that amoxicillin/clavulanate is the only drug             had ever received PCV-7, with good P values and con-
 of choice for de novo AOM with fever or moderate to                fidence intervals of 1.1 to 18.4.
 severe otalgia and for uncomplicated AOM that has                      As for the standard-dose of amoxicillin/clavulanate,
 failed to respond to initial antibiotic therapy.9 But for          children enrolled in the study were not otitis-prone and
 the penicillin-allergic child or one who presents with             had not failed prior antibiotic therapy for AOM, the
 vomiting, diarrhea, or an upset stomach, cefdinir                  clinical setting in which high-dose amoxicillin/clavu-
 would be the more appropriate choice. I believe it                 lanate should primarily be used at present. Another
 may be unwise to treat a child who has a fever and is              caveat to the data is that the mean age of 2.8 years for
 not drinking or not eating well with amoxicillin/                  our patient population was a bit high. Ideally, in an
 clavulanate. If amoxicillin/clavulanate is not taken               AOM trial most of the children should be younger
 with substantial food or milk, it will commonly pre-               than 2 years because they are the hardest to treat and
 cipitate gastrointestinal distress.                                they tend to have the most failures.22

 ASiM: Compared with standard-dose amoxi-                           ASiM: How would you differentiate some of the
 cillin/clavulanate given twice daily for 10 days,                  available cephalosporins?
 would you expect adherence to be better with                           Dr Block: Let us compare cefdinir with cefprozil,
 cefdinir given twice daily for 5 days and, if so,                  both of which are commonly used cephalosporins.
 why?                                                               Cefprozil provides mainly gram-positive coverage,
     Dr Block: Yes, I would expect adherence to be bet-             especially against pneumococcus, including peni-
 ter with the 5-day cefdinir regimen. Any time that                 cillin intermediate-resistant strains. However, cef-
 duration of the dosing can be shortened, adherence                 prozil     provides       minimal       coverage     for
 can be improved. As for efficacy, I would recommend                beta-lactamase–negative or –positive strains of H
 that for cefdinir, most clinicians should use a 10-day             influenzae. The time above the MIC90 (minimal
 once-daily regimen for children younger than 2 years               inhibitory concentration) for this pathogen is only
 and for those who are treatment failures. Clinical trial           21% of the dosage interval,23 less than half that
 experience with cefdinir and amoxicillin/clavulanate               reported for cefpodoxime and, presumably, cefdinir.
 suggests that a standard 10-day course of therapy is               In addition, cefprozil has minimal activity against
 preferable in younger children with AOM.20,21 The 5-               M catarrhalis; the MIC90 is 8 mg/mL compared to
 day twice-daily cefdinir regimen probably should be                that of 0.25 mg/mL for cefdinir.13 Therefore, in the
 used only in children older than 2 years or in those               era of PCV-7 where two thirds of the pathogens are
 with recurrent AOM who have not received antibiotics               gram-negative, cefprozil probably does not have a
 for at least a few weeks.                                          major role and may not be better than placebo in
                                                                    terms of efficacy.
 ASiM: Could you comment on what some col-                              Azithromycin, on the other hand, has some issues
 leagues believe are limitations of this study; name-               in terms of H influenzae coverage. Although
 ly, the fact that you used standard-dose                           azithromycin achieves concentrations in MEF that are
 amoxicillin/clavulanate and did not do tympa-                      consistently much higher than those in serum, it is
 nocentesis?                                                        believed by some to be tightly bound to the leckocytes.
    Dr Block: Those are the 2 biggest caveats to the                Two recent double tympanocentesis trials in children
 data. With regard to the fact that we did not do tym-              with uncomplicated AOM found that the standard
 panocentesis, some believe that clinical endpoints are             azithromycin regimen (10 mg/kg on day 1, then
 not reliable as far as differentiating efficacy between            5 mg/kg on days 2 through 5) failed to eradicate
 drugs. However, there have been other clinical trials              H influenzae from MEF obtained on treatment days 3
 such as ours in which the evaluation of drug efficacy              to 6 in at least half of the patients (87% vs 39%, P =
 using clinical endpoints, rather than tympanocentesis              .0001).24 The investigators suggest that the susceptibil-
 plus cultures of middle ear fluid (MEF), clearly demon-            ity breakpoints for H influenzae should be much lower

Advanced Studies in Medicine   I                                                                                       S941
                                                    CLINICIAN INTERVIEW

than at present for azithromycin. This would be con-                                     REFERENCES
sistent with the recent interpretation of Jacobs of sus-
ceptibility data for oral antibiotics using PK/PD                  1. Klein JO. Otitis media. Clin Infect Dis. 1994;19(5):823-833.
                                                                   2. Block SL, Hedrick J, Harrison CJ, et al. Community-wide
(pharmacokinetic/pharmacodynamic) parameters.25                        vaccination with heptavalent pneumococcal conjugate sig-
Using these criteria, virtually all H influenzae isolates              nificantly alters the microbiology of acute otitis media.
were susceptible to amoxicillin/clavulanate (98.3%),                   Pediatr Infect Dis J. 2004;23(9):829-833.
                                                                   3. Black S, Shinefeld H, Pireman B, et al. Efficacy, safety and
but only 5% were susceptible to cefaclor, azithromycin,                immunogenicity of heptavalent pneumococcal conjugate vac-
or clarithromycin.25 Thus, azithromycin may not be                     cine in children. Pediatr Infect Dis J. 2000;19(3):187-195.
particularly effective for the treatment of AOM due to             4. Fireman B, Black SB, Shinefeld HR, Lee J, Lewis E, Ray P.
                                                                       Impact of the pneumococcal conjugate vaccine on otitis
poor coverage of H influenzae at standard doses.
                                                                       media. Pediatr Infect Dis J. 2003;22(1):10-16. Erratum in:
                                                                       Pediatr Infect Dis J. 2003;22(2):163.
ASiM: Do future trials need to consider the PCV-7                  5. Black S, Shinefeld H, Baxter R, et al. Postlicensure surveil-
status of the children enrolled?                                       lance for pneumococcal invasive disease after use of hep-
                                                                       tavalent pneumococcal conjugate vaccine in Northern
    Dr Block: I believe it is imperative that all future               California Kaiser Permanente. Pediatr Infect Dis J.
clinical trials of AOM address the PCV-7 status of                     2004;23(6):485-489.
the children enrolled in studies. As I alluded to earli-           6. Block SL, Hedrick JA, Harrison CJ. Widespread use of con-
                                                                       jugated pneumococcal vaccine significantly reduces rates
er, the fourth or booster dose is probably much more                   of AOM and antibiotic usage. Presented at: the Society for
important for protection against mucosal disease.                      Pediatric Research; May 2004; San Francisco, Calif.
Most penicillin-resistant pneumococcal strains are                     Abstract 1135.
                                                                   7. Block SL, Harrison CJ, Hedrick J, Tyler R, Smith A, Hedrick
vaccine or vaccine-related serotypes. Our data suggest
                                                                       R. Restricted use of antibiotic prophylaxis for recurrent
that the PCV-7 status of the study population may                      acute otitis media in the era of penicillin non-susceptible
have a significant impact on the microbiologic and                     Streptococcus pneumoniae. Int J Pediatr Otorhinolaryngol.
efficacy data obtained during the trial. Furthermore,                  2001;61(1):47-60.
                                                                   8. Casey JR, Pichichero ME. Changes in frequency and
it may not be valid to compare data from US children                   pathogens causing acute otitis media in 1995-2003.
or those who have received PCV-7 with data from                        Pediatr Infect Dis J. 2004;23(9):824-828.
non-US children who have not received PCV-7.                       9. American Academy of Pediatrics/American Academy of
                                                                       Family Physicians Subcommittee on Management of Acute
Except for Israel, non-US children usually have lower                  Otitis Media. Clinical practice guideline: Diagnosis and
rates of infection due to H influenzae, particularly                   management of acute otitis media. Pediatrics.
beta-lactamase–positive strains.                                       2004;113(5):1451-1465.
                                                                   10. Physicians’ Desk Reference. 58th ed. Montvale, NJ:
                                                                       Thomson PDR; 2004.
ASiM: Do you believe that future AOM treatment                     11. Sader HS, Fritsche TR, Mutnick AH, Jones RN.
guidelines should consider the PCV-7 status of                         Contemporary evaluation of the in vitro activity and spec-
children, especially those aged 6 to 24 months?                        trum of cefdinir compared with other orally administered
                                                                       antimicrobials tested against common respiratory tract
    Dr      Block:     Definitely.     At      present                 pathogens (2000-2002). Diagn Microbiol Infect Dis.
amoxicillin/clavulanate is the only oral drug being                    2003;47(3):515-525.
recommended by the recent AAP/AAFP guidelines                      12. Pichichero ME. Acute otitis media: part II. Treatment in an
                                                                       era of increasing antibiotic resistance. Am Fam Physician.
for AOM that fails to respond to initial antibiotic                    2000;61(8):2410-2416.
therapy. In the gram-negative era of PCV-7, third-                 13. Dandekar PK, Nicolau DP. Pharmacodynamic considera-
generation cephalosporins cefdinir and cefpo-                          tions for the selection of oral cephalosporins in the treat-
                                                                       ment of rhinosinusitis. Otolaryngol Head Neck Surg.
doxime, both of which have good coverage of H
                                                                       2002;127(6, suppl):S10-S16.
influenzae and most pneumococcus, should be                        14. Steele RW, Thomas MP, Begue RE. Compliance issues
included as routine second- or third-line choices                      related to the selection of antibiotic suspensions for chil-
along with amoxicillin/clavulanate. But in all fair-                   dren. Pediatr Infect Dis J. 2001;20(1):1-5.
                                                                   15. Block SL, Busman TA, Paris MM, Bukofzer S. Comparison
ness, when the current AAP/AAFP guidelines were                        of 5 day cefdinir treatment with 10-day low dose amoxi-
developed, there were almost no data available on                      cillin/clavulanate treatment for acute otitis media. Pediatr
this microbial shift. Finally, because of its superior                 Infect Dis J. 2004;23(9):834-838.
                                                                   16. Block SL, Harrison CJ, Hedrick JA, et al. Penicillin-resistant
palatability and recent clinical trial data in PCV-                    Streptococcus pneumoniae in acute otitis media, risk fac-
7–vaccinated children, cefdinir has an advantage                       tors, susceptibility patterns and antimicrobial management.
over cefpodoxime liquid suspension.                                    Pediatr Infect Dis J. 1995;14(9):751-759.

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 17. Rodriguez WJ, Schwartz RH. Streptococcus pneumoniae                        21. Hoberman A, Paradise JL, Burch DJ, et al. Equivalent effi-
     causes otitis media with higher fever and more redness of                      cacy and reduced occurrence of diarrhea from a new for-
     tympanic membranes than Haemophilus influenzae or                              mulation of amoxicillin/clavulanate potassium (Augmentin)
     Moraxella catarrhalis. Pediatr Infect Dis.                                     for treatment of acute otitis media in children. Pediatr
     1999;18(10):942-943.                                                           Infect Dis J. 1997;16(5):463-470.
 18. Del Beccaro MA, Mendelman PM, Inglis AF, et al.                            22. Carlin SA, Marchant CD, Shurin PA, Johnson CE, Super DM,
     Bacteriology of acute otitis media: a new perspective. J                       Rehmus JM. Host factors and early therapeutic response in
     Pediatr. 1992;120(1):81-84.                                                    acute otitis media. J Pediatr. 1991;118(2):178-183.
 19. Piglansky L, Leibovitz E, Raiz S, et al. Bacteriologic and                 23. Jacobs MR. Optimisation of antimicrobial therapy using
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