Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae

Patel, Janak A.; Reisner, Barbara S.; Vizirinia, Negar; Owen, Mary; Chonmaitree, Tasnee; Howie, Virgil M.

doi:10.1016/s0022-3476(95)70415-9

Cited by 43 publications

(23 citation statements)

References 12 publications

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“…Furthermore, no significant difference in bacteriologic response rates was found between the isolates for which cefaclor MICs were low (0.38 to 1.0 g/ml) and those for which MICs were higher (1.5 to 3.0 g/ml). The high rate of persistence of H. influenzae in middle-ear fluid after 3 to 4 days of treatment with cefaclor is consistent with the rate reported in other studies (24,34,37): cefaclor had a lower bacteriologic eradication success rate than cefuroxime axetil (14,27), amoxicillin-clavulanate (34,41), cefixime (25,40), and ceftriaxone (27,32).…”

Section: Discussionsupporting

confidence: 88%

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

Dagan

Leibovitz

Fliss³

et al. 2000

Antimicrob Agents Chemother

125

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A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae.By definition, the goal of antibiotics in the treatment of acute otitis media (AOM) is eradication of the causative organism from the middle-ear fluid. In order to reach this goal, two conditions must be met: (i) the drug should be active against the causative organisms, and (ii) the drug should reach the middle-ear fluid and maintain a sufficient concentration long enough to allow bacterial inhibition and eventual killing (11). Although these two conditions can be tested in animal models, the ultimate challenge is the eradication of the pathogens from humans and, more specifically, from infants and young children, since they constitute the majority of patients with AOM.Unfortunately, the pharmacodynamic profiles of antimicrobial drugs (i.e., the relationship between concentrations at the site of infection over time and the antimicrobial effect) may not always be determined with accuracy in infants and young children, for obvious reasons. Thus, eradication of the pathogens must be studied in infants and children with AOM. Pathogen eradication can be assessed by performing trials in which a middle-ear fluid sample for culture is obtained immediately before antibiotic administration and a second one is obtained during the course of treatment (35). Howie and Ploussard (23) were the first to introduce this method and named it the "in vivo sensitivity test." The advantage of this method is that, with relatively few enrolled subjects, it can discriminate the effects of different drugs and predict clinical efficacy (13, 14, 23-26, 34, 35).The recent increase in the prevalence of antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis has important implications for the treatment of AOM and poses a challenge to clinicians (5,7,13,18,21,25,28,33,48,49 1996). We recently demonstrated that in patients with AOM caused by S. pneumoniae isolates not susceptible to ␤-lactam antibiotics, the bacteriologic outcome was unsatisfactory in patients treated with various ␤-lactam antibiotics 13, 14, 32; Leibovitz et al., 36th ICAAC). The introductio...

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Section: Discussionsupporting

confidence: 88%

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

Dagan

Leibovitz

Fliss³

et al. 2000

Antimicrob Agents Chemother

125

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“…Since 1980, a marked increase has been reported in the isolation of M. catarrhalis from middle-ear exudates (26,141,155,213). This increase in M. catarrhalis isolation to approximately 15 to 20% (187) has been accompanied by the appearance of ␤-lactamase-producing strains, which now account for approximately 90 to 95% of isolates. However, the exact magnitude of this apparent increase in isolation rates may not have been adequately measured yet (155), since tympanocentesis and culture of middle ear fluid are not performed routinely.…”

Section: Otitis Mediamentioning

confidence: 99%

“…However, the exact magnitude of this apparent increase in isolation rates may not have been adequately measured yet (155), since tympanocentesis and culture of middle ear fluid are not performed routinely. Patel et al (187) cultured the middle ear fluids of 99 children with AOM and isolated S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis from 39, 30, and 25% of subjects, respectively. Again, the isolation rates for M. catarrhalis might be an underestimation, given the relatively anaerobic environment of the middle ear during infection (8).…”

Section: Otitis Mediamentioning

confidence: 99%

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Moraxella catarrhalis: from Emerging to Established Pathogen

et al. 2002

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SUMMARY Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of Β-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen.

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“…M. catarrhalis is the third leading cause of otitis media after Streptococcus pneumoniae and nontypeable Haemophilus influenzae (21,34). M. catarrhalis is associated with up to 25% of acute otitis media cases by culture (37) and 46.4% of chronic middle ear effusion cases by PCR (41). In addition, the nasopharyngeal carriage rate of M. catarrhalis in children is high (up to 75%) and the frequency of colonization is positively related to the development of otitis media (14).…”

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confidence: 99%

Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen

2011

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Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis.Moraxella catarrhalis is a Gram-negative diplococcus frequently found as a commensal of the upper respiratory tract (14,19). However, over the past 2 to 3 decades this bacterium has shifted from being considered a harmless commensal to being recognized as a genuine respiratory tract pathogen of serious public health concern (34, 54).Acute otitis media is the most common bacterial infection in children, with 70% experiencing at least one episode by age 3 (53). M. catarrhalis is the third leading cause of otitis media after Streptococcus pneumoniae and nontypeable Haemophilus influenzae (21,34). M. catarrhalis is associated with up to 25% of acute otitis media cases by culture (37) and 46.4% of chronic middle ear effusion cases by PCR (41). In addition, the nasopharyngeal carriage rate of M. catarrhalis in children is high (up to 75%) and the frequency of colonization is positively related to the development of otitis media (14).In adults, M. catarrhalis is the second most common bacterial cause of exacerbations of chronic obstructive pulmonary disease (COPD) after nontypeable H. influenzae (33,48,49). COPD is the fourth leading cause of death in the United States, affecting 24 million Americans (25, 26). M. catarrhalis causes approximately 10% of exacerbations of COPD, accounting for 2 to 4 million episodes annually (33). Furthermore, M. catarrhalis also colonizes the lower respiratory tract in up to 2.5 to 10% of adults with COPD at their stable states (31, 59). Lower airway colonization contributes to airway inflammation in COPD as a result of sloughing of highly inflammatory bacterial cell wall antigens into the airway (49).The significant clinical implications of M. catarrhalis require a vaccine targeting bo...

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Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae

Cited by 43 publications

References 12 publications

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

Moraxella catarrhalis: from Emerging to Established Pathogen

Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen

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