Antimicrobial resistance in the nasopharyngeal flora of children with acute maxillary sinusitis and maxillary sinusitis recurring after amoxicillin therapy

Itzhak Brook* and Alan E. Gober

Department of Pediatrics, Georgetown University School of Medicine, 4431 Albemarle St. NW, Washington, DC 20016, USA

Received 27 August 2003; returned 14 October 2003; revised 2 November 2003; accepted 7 November 2003


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Objective: To investigate the antimicrobial susceptibility of the organisms isolated from the nasopharynx of children who present with acute maxillary sinusitis (AMS) or maxillary sinusitis that recurred (RMS) after amoxicillin therapy.

Methods: Analysis of nasopharyngeal cultures obtained from 70 patients, 42 with AMS and 28 with RMS.

Results: Thirty-eight potentially pathogenic organisms were recovered in 36 (86%) of the children from the AMS group, and 40 were isolated from 26 (93%) of the children from the RMS group. The organisms isolated were Streptococcus pneumoniae (21 isolates), Haemophilus influenzae non-type b (17), Moraxella catarrhalis (15), Streptococcus pyogenes (13) and Staphylococcus aureus (12). Resistance to the eight antimicrobial agents used was found in 34 instances in the AMS group compared to 93 instances in the RMS group (P < 0.005). The difference between AMS and RMS was significant with S. pneumoniae resistance to amoxicillin (P < 0.0025), to co-amoxiclav (P < 0.0025), to trimethoprim–sulfamethoxazole (P < 0.05), to cefixime (P < 0.05), and to azithromycin (P < 0.05), and for H. influenzae to amoxicillin (P < 0.025).

Conclusions: These data illustrate the higher recovery rate of antimicrobial-resistant S. pneumoniae and H. influenzae from the nasopharynx of children who had maxillary sinusitis that recurred after amoxicillin therapy than those with AMS.

Keywords: sinusitis, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, antimicrobial resistance


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The growing resistance to antimicrobial agents of all respiratory tract bacterial pathogens has made the management of acute sinusitis more difficult. The upper respiratory tract including the nasopharynx serves as the reservoir for pathogenic bacteria that can cause respiratory infections including sinusitis.1 Potential pathogens can relocate during a viral respiratory infection, from the nasopharynx into the sinus cavity, causing sinusitis. Failure of antimicrobials to clear the nasopharynx from potential pathogens can be the result of their antimicrobial resistance and can allow them to survive and initiate a recurrence of the infection.2

This study was carried out to investigate the antimicrobial susceptibility of the organisms isolated from the nasopharynx of children who present with maxillary sinusitis or maxillary sinusitis that recurred after amoxicillin therapy.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The study was conducted between September 1, 1997 and August 2001 in a community clinic setting. The population studied was middle class, residing in suburban locations near Washington, DC, USA. Included were all children who presented with acute maxillary sinusitis (AMS) or recurrent maxillary sinusitis (RMS) following amoxicillin therapy. All presented with clinical signs of active infection.

The diagnostic criteria applied for maxillary sinusitis were the presence of purulent rhino-sinusitis for at least 10 days and radiological abnormalities of the maxillary sinus in the form of total opacity or mucosal swelling greater than 6 mm (established by plain film or computed tomography). These were carried out as previously described.3 RMS was defined as an AMS episode that followed a previous maxillary sinus infection after an infection-free interval of 4–6 weeks. All patients of the RMS group were treated with amoxicillin (45 mg/kg per day) given twice a day for 14 days for their previous infection. Excluded were children who had ear effusion or infection, otorrhoea, tympanostomy tubes, craniofacial anomalies, chronic sinusitis and other chronic medical problems. Also excluded from the AMS group were those who had received antimicrobials in the past 3 months.

A total of 70 patients were studied, 42 with AMS and 28 with RMS. Patient ages ranged from 3 years and 8 months to 13 years and 5 months (average age 8 years and 9 months) and 41 were males. No differences were noted in the age, gender and day care attendance distribution between the two groups. No siblings were allowed to be included in the study.

Nasopharyngeal cultures were obtained using sterile calcium alginate swabs and were immediately plated on media supportive of growth of aerobic and facultative anaerobes. Sheep blood agar, chocolate agar and MacConkey agar plates were inoculated. The plates were incubated at 37°C aerobically (MacConkey) or under 5% CO2 and examined at 24 and 48 h. Potentially pathogenic organisms (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Staphylococcus aureus) were identified by techniques described previously.4 ß-Lactamase activity was determined on all isolates by the nitrocefin method.4

MICs of eight antimicrobial agents were determined (Table 1) by the agar dilution method with Mueller–Hinton agar (BBL Microbiology Systems, Cockeysville, MD, USA) supplemented with 5% sheep blood. The NCCLS breakpoints were used for MIC interpretation.5 For MIC determinations, suspensions with a turbidity equivalent to that of a 0.5 McFarland standard were prepared by suspending growth from blood agar plates in 2 mL of Mueller–Hinton broth (BBL). Suspensions were further diluted 1:10 to obtain a final inoculum of 104 cfu/spot. Plates were inoculated with a Steers replicator and incubated overnight in ambient air at 37°C. Standard quality control strains were included in each run. Additionally, MICs of azithromycin were read after an additional 24 h of incubation. Intermediate resistance to penicillin was defined as an MIC of 0.1–1.0 mg/L and high resistance to penicillin was defined as an MIC of 2.0 mg/L. Statistical analysis was done using the t-test and the {chi}2 test with continuity correction.


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Table 1. Number of resistant isolates (%) recovered from the nasopharynx of 42 children with AMS and 28 with RMS
 

    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Thirty-eight potentially pathogenic organisms were recovered in 36 (86%) of the children from the AMS group, and 40 were isolated from 26 (93%) of the children from the RMS group. The organisms isolated were S. pneumoniae (21 isolates, 11 in AMS and 10 in RMS), H. influenzae non-type b (17 isolates, eight in AMS and nine in RMS), M. catarrhalis (15 isolates, seven in AMS and eight in RMS), S. pyogenes (13 instances, seven in AMS and six in RMS), and S. aureus (12 instances, five in AMS and seven in RMS) (Table 1). All amoxicillin-resistant H. influenzae and M. catarrhalis produced ß-lactamase.

Of the two penicillin-resistant S. pneumoniae isolates recovered in the AMS group, one was intermediately resistant and one was highly resistant. Of the eight S. pneumoniae isolates in the RMS group, five were intermediately resistant and three highly resistant.

Resistance to the eight antimicrobial agents used was found in 34 instances (of a total of 304 possibilities) in the AMS group compared to 93 instances (of a total of 320 possibilities) in the RMS group (P < 0.005) (Table 1). The difference between AMS and RMS was significant with S. pneumoniae resistance to amoxicillin (P < 0.0025), to co-amoxiclav (P < 0.0025), to trimethoprim–sulfamethoxazole (P < 0.05), to cefixime (P < 0.05), and to azithromycin (P < 0.05), and for H. influenzae to amoxicillin (P < 0.025) (Table 1).


    Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
These data illustrate the higher recovery rate of antimicrobial-resistant S. pneumoniae and H. influenzae from the nasopharynx of children who had RMS compared to those with AMS. The increased resistance is toward a broad range of antimicrobials which include amoxicillin, co-amoxiclav, trimethoprim–sulfamethoxazole, cefixime and azithromycin. Previous amoxicillin treatment might have selected for resistance that could have persisted in the nasopharynx to re-emerge in the new maxillary sinus infection. The emergence of strains that are resistant to multiple antibiotics other than amoxicillin has been previously described and is believed to be the result of the selective pressure that allows the survival of multiresistant organisms.

These findings support previous reports where such a relationship was found in recovery of pathogens from middle ear aspirates in children.6,7 Brook & Gober7 evaluated the antimicrobial susceptibility of the pathogens isolated from the middle ear of 22 children with otitis media and from sinus aspirates of 20 patients with maxillary sinusitis who failed to respond to antimicrobial therapy and correlated it with previous antimicrobial therapy. Resistance of at least two tube dilutions (tested in parallel) to the antimicrobial agents used was found in 23 of the 47 (49%) isolates that were found in 20 (48%) of the patients. These included 10 of 15 (67%) isolates of S. pneumoniae, four of 14 (29%) H. influenzae, four of seven (57%) S. aureus, and five of six (83%) M. catarrhalis. A statistically significant higher recovery of resistant organisms was noted in those treated 2–6 months previously, and in those with sinusitis who smoked. The data illustrate the relationship between resistance to antimicrobials and failure of patients with otitis media and sinusitis to improve.

S. pneumoniae, H. influenzae and M. catarrhalis are showing increasing resistance to a variety of antibiotics. S. pneumoniae has growing resistance to penicillin, orally administered third generation cephalosporins (i.e. cefixime), trimethoprim–sulfamethoxazole and the macrolides and H. influenzae and M. catarrhalis resist ß-lactam antibiotics through the production of ß-lactamase.8 Selection of antimicrobial agents can be improved by knowledge of the resistance pattern of the organisms in the community and by consideration of the effect of previous antimicrobial therapy or prophylaxis9 that may select resistant strains. Increased resistance to several antimicrobials can be expected in children with RMS who had failed antimicrobial therapy. The selective use of collection of endoscopic sinus aspirates for smear, culture and susceptibility studies, can assist in the proper selection of antimicrobial therapy.10


    Footnotes
 
* Corresponding author. Tel: +1-301-295-2698; Fax: +1-253-981-8709; E-mail: ib6{at}georgetown.edu Back


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Faden, H., Stanievich, J., Brodsky, L. et al. (1990). Changes in the nasopharyngeal flora during otitis media of childhood. Pediatric Infectious Disease 9, 623–6.[ISI]

2 . Dagan, R., Leibovitz, E., Cheletz, G. et al. (2001). Antibiotic treatment in acute otitis media promotes superinfection with resistant Streptococcus pneumoniae carried before initiation of treatment. Journal of Infectious Diseases 183, 880–6.[CrossRef][ISI][Medline]

3 . Brook, I., Frazier, E. H. & Foote, P. A. (1996). Microbiology of the transition from acute to chronic maxillary sinusitis. Journal of Medical Microbiology 45, 372–5.[Abstract]

4 . Murray, P. R., Baron, E. J., Pfalter, M. A. et al. (1999). Manual of Clinical Microbiology, 7th edn. American Society for Microbiology, Washington, DC, USA.

5 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—5th Edition: Approved Standard M7-A5. NCCLS, Wayne, PA, USA.

6 . Dagan, R., Abramson, O., Leibovitz, E. et al. (1996). Impaired bacteriologic response to cephalosporins in acute otitis media caused by pneumococci with intermediate resistance to penicillin. Pediatric Infectious Disease Journal 15, 980–5.[CrossRef][ISI][Medline]

7 . Brook, I. & Gober, A. E. (1999). Resistance to antimicrobials used for the therapy of otitis and sinusitis: effect of previous antimicrobial therapy and smoking. Annals of Otology, Rhinology and Laryngology 108, 645–7.[ISI][Medline]

8 . Ednie, L. M., Spangler, S. K., Jacobs, M. R. et al. (1997). Susceptibilities of 228 penicillin- and erythromycin-susceptible and -resistant pneumococci to RU 64004, a new ketolide, compared with susceptibilities to 16 other agents. Antimicrobial Agents and Chemotherapy 41, 1033–6.[Abstract]

9 . Brook, I. & Gober, A. E. (1996). Prophylaxis with amoxicillin or sulfisoxazole for otitis media: effect on the recovery of penicillin-resistant bacteria from children. Clinical Infectious Diseases 22, 143–5.[ISI][Medline]

10 . Brook, I., Frazier, E. H. & Foote, P. A. (1997). Microbiology of chronic maxillary sinusitis: comparison between specimens obtained by sinus endoscopy and by surgical drainage. Journal of Medical Microbiology 46, 430–2.[Abstract]