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PubMed1988

Cost effectiveness of antibiotic therapy for otitis media in a military pediatric clinic.

Amoxicillin continues to be the drug of first choice in the treatment of acute otitis media in children, because it is generally considered to be the safest and least expensive of the available choices. However, amoxicillin may not be the most cost-effective therapy in some settings because of its decreasing efficacy and moderately high rate of minor adverse effects. In this review, the cost effectiveness of antibiotics used to treat otitis media in a large military pediatric clinic are compared, using the decision analysis method. With this model, trimethoprim-sulfamethoxyazole is more cost-effective than amoxicillin, and cefaclor, given twice a day for 5 days, is the next most cost-effective regimen. In addition, the major and minor adverse effects of each of the agents are compared and the additional impact on cost effectiveness is considered.

Acute Disease↗
PubMed1993

Review of cefixime in the treatment of otitis media in infants and children.

During the past decade there has been an increase in the percentage of resistant bacteria isolated from middle-ear effusions aspirated from infants and children who have had acute otitis media. At least nine oral antibiotics or combination agents are available for this indication. Cefixime, a third generation cephalosporin, has excellent in vitro activity against both beta-lactamase-negative and beta-lactamase-positive Haemophilus influenzae and Moraxella catarrhalis, good activity against Streptococcus pneumoniae and Streptococcus pyogenes but relatively poor activity against Staphylococcus aureus. In children cefixime is similar in effectiveness to amoxicillin and cefaclor, but diarrhea and stool changes are more common with cefixime. Amoxicillin is still preferred for initial empiric treatment of uncomplicated acute otitis media. Its major drawback is limited efficacy when beta-lactamase-producing bacteria are the causative organisms. Cefixime is a viable alternative to amoxicillin for infants and children with acute otitis media when: (1) a beta-lactamase-producing H. influenzae or M. catarrhalis is isolated from otorrhea or tympanocentesis; (2) the child has a history of delayed hypersensitivity to the penicillins but no history of hypersensitivity to the cephalosporins; (3) there is a high incidence of resistant bacteria in the community; (4) there is not clinical improvement with amoxicillin; or (5) once daily administration is more convenient.

Animals↗
PubMed1993

Overview of the safety profile of clarithromycin suspension in pediatric patients.

Results of preclinical studies conducted to characterize the safety of clarithromycin oral suspension in juvenile mice, rats and dogs as compared with that in adult animals indicate that there is no enhanced risk in younger animals. Adverse events in these preclinical studies mainly involved decreased body and increased liver and kidney weights. The safety profile of clarithromycin suspension also has been evaluated in Phase II (pharmacokinetic) and III (clinical) United States and international clinical trials conducted in pediatric patients. The most frequently reported adverse events occurring among the 1676 patients studied who received clarithromycin suspension in Phase III trials included diarrhea (7%), vomiting (6%), abdominal pain (2%), headache (2%) and nausea (1%). Adverse events were not serious and were usually rapidly reversible. Adverse event rates did not vary with sex or race. Overall adverse event rates were generally similar to those of comparator beta-lactam suspensions (i.e. amoxicillin, amoxicillin/clavulanate, penicillin VK, cefaclor, cefadroxil). With regard to specific gastrointestinal events, however, clarithromycin was better tolerated than amoxicillin/clavulanate whereas penicillin VK showed a lower incidence of gastrointestinal events. Overall clarithromycin oral suspension appears to be safe and well-tolerated, making it suitable for use in the pediatric population.

Animals↗
PubMed1994

Antimicrobial susceptibility of nasopharyngeal isolates of potential pathogens recovered from infants before antibiotic therapy: implications for the management of otitis media.

Antimicrobial susceptibility was determined for strains of Streptococcus pneumoniae, nontypable Haemophilus influenzae and Moraxella catarrhalis recovered from the nasopharynxes of children followed from birth. The bacteria tested were the first potential pathogens isolated from each child before any treatment with antibiotics. Minimal inhibitory concentrations of commonly used oral antibiotics demonstrated the following overall rates of resistance for (1) S. pneumoniae: penicillin 1.2% (intermediate susceptibility 4.8%), trimethoprim-sulfamethoxazole 20%; (2) nontypable H. influenzae: ampicillin 32%, cefaclor 17%; (3) M. catarrhalis: ampicillin 90%, trimethoprim-sulfamethoxazole 19%. Antibiotic regimens used for treatment of otitis media may have to be evaluated in light of changing antibiotic susceptibilities.

Anti-Bacterial Agents↗
PubMed1995

Persistent acute otitis media: II. Antimicrobial treatment.

In this three-year prospective study, 137 children with acute otitis media (AOM) that had not responded after one or two empiric antimicrobial treatment courses (termed persistent AOM) underwent tympanocentesis to determine additional antimicrobial therapy based on in vitro susceptibility testing of the bacterial isolate(s). One hundred eleven children with AOM not previously treated are described for comparison. In the persistent AOM group middle ear aspirates grew Streptococcus pneumoniae (24%), Haemophilus influenzae (7%), Brahamella catarrhalis (7%), Streptococcus pyogenes (6%), Staphylococcus aureus (5%), two pathogens (3%) or no bacterial growth (49%); pathogens in previously untreated AOM were similar but fewer patients (30%) had no bacterial growth. After tympanocentesis additional antimicrobial therapy for persistent AOM patients utilizing drugs shown to be effective in vitro against the isolated pathogen failed to produce clinical resolution of infection in 27 (28%) of ears. Differing clinical efficacy was observed with various antimicrobials: amoxicillin (57% failure); trimethoprim/sulfamethoxazole (75% failure); cefaclor (37% failure); cefixime (23% failure); amoxicillin/clavulanate (12% failure); and cefuroxime axetil (13% failure). Presumptive clinical cure for previously untreated AOM patients was similar to that for untreated AOM except for fewer amoxicillin failures (30%). We conclude that clinical failure in persistent AOM occurs (1) even when no pathogen is isolated from tympanocentesis (50% of patients) and (2) despite demonstrated in vitro activity against culture-proved pathogens.

Acute Disease↗
PubMed1995

Clinical experience with cefpodoxime proxetil in acute otitis media.

Although it varies from country to country, there is a worrying worldwide increase in antibiotic resistance among pathogens causing otitis. This has led to a search for therapeutic alternatives to the reference treatment, which is still amoxicillin in many countries. Cefpodoxime proxetil is one such alternative. Six comparative randomized trials of cefpodoxime proxetil in childhood acute otitis media have been published or presented at international conferences. They involved a total of 1188 patients, 658 of whom received cefpodoxime proxetil and 530 of whom received the comparator drug (amoxicillin/clavulanic acid in 3 trials, cefaclor in 1, and cefixime in 2); duration of treatment varied from 5 days for cefpodoxime proxetil to 10 days for amoxicillin/clavulanic acid, and the age of the children included ranged from 2 months to 12 years. The clinical efficacy of cefpodoxime proxetil was at least equivalent to that of the comparators in 4 trials and significantly better in 2 trials. Firstly, in one study vs. amoxicillin/clavulanic acid, the superiority of cefpodoxime proxetil (8 mg/kg/day twice daily) in terms of healing at the end of treatment and in terms of the number of normal tympanograms at the follow-up visit was shown. Secondly, in a study performed by our group, vs. cefixime, cefpodoxime proxetil (8 mg/kg/day twice daily) showed a better healing rate at the end of treatment in febrile and painful acute otitis media. The microbiologic and pharmacokinetic data show that cefpodoxime proxetil is one of the most active compounds against Haemophilus influenzae and Streptococcus pneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Resistance among problem respiratory pathogens in pediatrics.

During the past two decades, the prevalence of beta-lactamase production with nontypable strains of Haemophilus influenzae has increased to about 35%. Fortunately, rates of resistance to other oral antimicrobials have not developed at a comparable pace. Amoxicillin/clavulanate, cefuroxime and cefpodoxime remain nearly uniformly active whereas rates of resistance to tetracycline, trimethoprim/sulfamethoxazole, chloramphenicol, cefaclor, loracarbef, cefprozil, azithromycin and clarithromycin remain low (1 to 5%). Virtually all clinical isolates of Moraxella catarrhalis produce beta-lactamase and are probably resistant to ampicillin and amoxicillin. However, alternative oral antimicrobials are almost always active. A compelling problem facing pediatricians today is the emergence of penicillin resistance with clinical isolates of Streptococcus pneumoniae. Currently, 15 to 25% of pneumococcal isolates in the United States have either intermediate (10 to 20%) or complete (3 to 5%) penicillin resistance caused by alterations in penicillin-binding proteins. Loss of activity of other beta-lactams is observed with penicillin-resistant S. pneumoniae. Third generation cephalosporins retain sufficient activity to warrant use in selected pneumococcal infections, even those caused by completely penicillin-resistant strains. Unfortunately, strains of S. pneumoniae with further alterations in penicillin-binding proteins have emerged such that even extended spectrum third generation cephalosporins lack activity. Rates of resistance to non-beta-lactam agents are also changing. The consequence of these changing patterns of resistance is that therapeutic options for pneumococcal infections in some patients are becoming increasingly limited.

Anti-Bacterial Agents↗
PubMed1998

Influence of recent antibiotic therapy on antimicrobial resistance of Streptococcus pneumoniae in children with acute otitis media in Spain.

BACKGROUND: Despite the high prevalence of penicillin resistance among Streptococcus pneumoniae strains in Spain (40 to 60% with MIC > or = 0.1 microg/ml), the data on acute otitis media (AOM) isolates are scarce. We conducted a prospective, longitudinal study to determine the rates of antimicrobial resistance of S. pneumoniae isolates from children with AOM in our country and to analyze the effect of previous antibiotic therapy on these rates. METHODS: Tympanocentesis was performed on 169 children diagnosed with AOM (age range, 1 month to 14 years). Two groups were considered: Group A, 113 patients with non-antibiotic-treated AOM, subdivided into Group A1 (collected from 1989 to 1992) and Group A2 (1992 to 1996); Group B, 56 patients from the period 1992 to 1996, with AOM clinical failure, defined as worsening or persistent symptoms after at least 2 days of appropriate antibiotic therapy. Amoxicillin-clavulanate was the most frequent antibiotic used (68%), followed by azithromycin (21%), cefaclor and cefixime (11%). RESULTS: A total of 63 S. pneumoniae isolates were recovered, 42 in Group A and 21 in Group B. Resistance to penicillin (MIC > or = 0.1 microg/ml) was found in 38% of strains in Group A (32% in A1 and 50% in A2), but in Group B the rate of resistance reached 90% (P = 0.0002). Erythromycin resistance was also increased from 35% (Group A2) to 62% (Group B), and trimethoprim-sulfamethoxazole resistance rose from 64% to 81%. CONCLUSIONS: Resistance to penicillin among S. pneumoniae AOM isolates is frequent and is increasing in Spain. After failure of standard antibiotic therapy, the rates of penicillin resistance reached 90% of the isolates.

Acute Disease↗
PubMed1998

Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients.

BACKGROUND: Nasopharyngeal (NP) carriage of antibiotic-resistant Streptococcus pneumoniae was shown to be associated with recent antibiotic treatment. To date no studies have evaluated early dynamics of pneumococcal NP carriage during antibiotic treatment. OBJECTIVES: To observe changes in NP pneumococcal carriage within 3 to 4 days after initiation of antibiotic treatment in acute otitis media (AOM). METHODS: Patients ages 3 to 36 months with AOM treated with various antibiotics were prospectively followed. Nasopharyngeal culture for S. pneumoniae was obtained before (Day 1) and 72 to 96 h after initiation of treatment (Days 4 to 5). Antibiogram and serotyping were performed in all isolates as was also the MIC of penicillin. The disappearance and persistence of the initial isolates as well as the appearance of isolates with new serotype or with new antibiotic susceptibility patterns were investigated. RESULTS: A total of 120 patients were studied: 106 received beta-lactam antibiotics and 14 received azithromycin. Among the initial 76 pneumococcal isolates 63, 37 and 13% were resistant to > or =1, > or =2 and > or =3 antibiotic drugs. After 3 to 4 days of treatment with various beta-lactam drugs, 45, 63 and 100% of isolates with MIC values of <0.1 microg/ml, 0.125 to 0.25 microg/ml and 0.38 to 1.0 microg/ml, respectively, persisted in the NP (P = 0.038). There was a difference between the various beta-lactam drugs in their effect on NP colonization: a drug with lower MIC values (cefuroxime-axetil) had a better eradication rate of penicillin-susceptible organisms than a less active one (cefaclor), but neither significantly reduced carriage of penicillin nonsusceptible isolates. Azithromycin eliminated carriage of macrolide-susceptible organisms but increased the carriage of macrolide-resistant ones. In 19 of 120 (16%) patients a new S. pneumoniae isolate was recovered 3 to 4 days after initiation of treatment. Of those 16 (84%) were resistant to the drug the patient was receiving. CONCLUSION: A rapid selection of nonsusceptible NP pneumococcal isolates during antibiotic treatment for AOM is common. This phenomenon may contribute to the spread of resistant pneumococci.

Acute Disease↗
PubMed1998

Bacteriologic efficacy of a three-day intramuscular ceftriaxone regimen in nonresponsive acute otitis media.

OBJECTIVE: To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children. METHODS: In a prospective study 92 patients ages 3 to 36 months (median, 11 months) with culture-proved nonresponsive acute otitis media were studied from January, 1995, through August, 1997. The patients were treated with intramuscular ceftriaxone (50 mg/kg/l/day) for 3 days. Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment (Day 1); a second tap was performed on Days 4 to 10. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive culture on Days 4 to 10. Patients were followed until Day 17+/-2. Susceptibility was measured by E test. RESULTS: The main drugs administered before enrollment were amoxicillin (38%), amoxicillinclavulanate (25%) and cefaclor (20%). Organisms recovered (n=105) were: Haemophilus influenzae, 54; Streptococcus pneumoniae, 47; Moraxella catarrhalis, 2; and Streptococcus pyogenes, 2. Thirty-four (72%) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin (MIC 0.1 to 1.0 microg/ml), but all were susceptible to ceftriaxone (MIC < 0.5 microg/ml). Bacteriologic eradication was achieved in 100 of 105 (95%) cases: 54 of 54 (10O%) H. influenzae, 43 of 47 (92%) S. pneumoniae, 1 of 2 (50%) M. catarrhalis and 2 of 2 (100%) S. pyogenes. Bacteriologic success (with no relapse) occurred in 13 of 13 (100%) penicillin-susceptible S. pneumoniae vs. 28 of 34 (82%) S. pneumoniae intermediately resistant to penicillin (4 cases of bacteriologic failure and 2 cases of relapse). CONCLUSION: A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media. The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined.

Acute Disease↗
PubMed2000

Antimicrobial resistance of Streptococcus pneumoniae isolated from healthy children in day-care centers: results of a multicenter study in Russia.

BACKGROUND: It has been previously shown that study of susceptibility of nasopharyngeal isolates in healthy carriers can predict resistance in clinical isolates. The purpose of this multicenter study was to determine the carriage rate of Streptococcus pneumoniae in healthy children attending day-care centers in Moscow, Smolensk and Yartsevo, Russia, and in vitro activity of penicillin G, amoxicillin/clavulanate, cefaclor, erythromycin, roxithromycin, clarithromycin and trimethoprim-sulfamethoxazole (TMP-SMX) against representative isolates. METHODS: Included in this study were 305 pneumococcal isolates from 733 children attending 9 day-care centers in Moscow, Smolensk and Yartsevo. All children enrolled in this study were <7 years of age. MICs of selected antimicrobials were determined by Etest. Serotyping of selected pneumococcal isolates was done with pool and type antisera. RESULTS: The carriage rate of S. pneumoniae in the 3 centers varied from 44.9% to 66.0% (mean, 55.9%). Susceptibility testing was performed with 305 (74.4%) of 410 isolates. Only 23 (7.5%) of 305 pneumococcal isolates were penicillin-intermediate (range, 2.8 to 12.8%) with no penicillin-resistant strains. All tested pneumococci were susceptible to amoxicillin/clavulanate. Macrolides possessed comparable activity against S. pneumoniae, at 4.6% resistant strains for both erythromycin (range, 1.1 to 17.1%) and clarithromycin (range, 1.7 to 17.1%). The highest level of resistance was observed with TMP-SMX, 53.4% (range, 43.8 to 70.9%). Of 23 strains 20 (87.0%) with intermediate resistance to penicillin were serotyped. The most prevalent serotype was 14 (5 isolates), followed by serogroups 19 (4) and 23 (4). CONCLUSIONS: Resistance to penicillin, other beta-lactams and macrolides does not seem to be a problem for Russia now. The high level of resistance to TMP-SMX considerably restricts its usage for the treatment of pneumococcal infections.

Child Day Care Centers↗
PubMed2002

Mycobacterium bohemicum cervical lymphadenitis.

A lymph node excision was performed on a 2-year-old child with right submandibular swelling not responding to oral cefaclor therapy. Histology revealed granulomatous, partly necrotizing lymphadenitis and a large number of acid-fast bacilli subsequently identified by molecular techniques as Mycobacterium bohemicum.

Antitubercular Agents↗
PubMedDate not supplied

Auxotypes and antibiotic susceptibilities of Neisseria gonorrhoeae from women with acute salpingitis. Comparison with gonococci causing uncomplicated genital tract infections in women.

An investigation of the MICs of various antibiotics and the nutritional requirements (auxotypes) of Neisseria gonorrhoeae recovered from the cervix, fallopian tubes, and peritoneal cavity of women with acute salpingitis was done. These MICs and auxotypes were compared to those of gonococci isolated from the cervix of women with uncomplicated or asymptomatic genital tract gonorrhea. The MICs of minocycline, penicillin G, ampicillin, cefoxitin, and cefaclor for gonococci isolated from women with acute salpingitis were significantly higher. Significant differences in auxotype patterns were identified between isolates from salpingitis cases and uncomplicated cases. The prototrophic form was the most common (75%) among salpingitis strains. No strains requiring arginine, hypoxanthine, and uracil were identified among the salpingitis isolates. In contrast, strains that required these nutrients were the most frequent auxotype among isolated from women with uncomplicated genital tract gonorrhea. Discriminant analysis revealed that the MIC of minocycline and the auxotype were the most powerful discriminators between groups of patients with different manifestations of gonorrhea.

Acute Disease↗
PubMedDate not supplied

Susceptibility of penicillinase-producing and non-penicillinase-producing strains of Neisseria gonorrhoeae isolated in Durban, South Africa, to 15 beta-lactam antibiotics.

Using two different inoculum sizes (10(4) and 10(7) organisms), we tested 35 penicillinase-producing (PPNG) and 72 non-PPNG strains of Neisseria gonorrhoeae falling into three categories (penicillin-sensitive, intermediately resistant, and resistant) by the agar-dilution method against 15 beta-lactam antibiotics. With the exception of penicillin, ampicillin, amoxicillin, and cephradine, the isolates were uniformly sensitive to all the other antibiotics tested (including spectinomycin, tetracycline, rosoxacin, sulfamethoxazole-trimethoprim [19:1 ratio], and kanamycin). Ceftriaxone and cefotaxime were the two most active compounds tested; all strains were inhibited at concentrations of 0.007 and 0.015 microgram/ml, respectively. Isolates with intrinsic resistance to penicillin were less susceptible to cefoxitin and cefuroxime than were PPNG strains. The effect of inoculum size varied for the different antibiotics; penicillin and cefaclor showed this effect only with PPNG strains, whereas for ampicillin and amoxicillin it was also seen with non-PPNG strains. Cephamandole showed this effect with both penicillin-sensitive and PPNG strains. In view of the increasing resistance to penicillin, we would recommend that alternative drugs be used as first line therapy for gonorrhea in South Africa.

Anti-Bacterial Agents↗
PubMed1991

Haemophilus influenzae resistance in a community hospital.

We prospectively tabulated all isolates of Haemophilus influenzae at DeKalb Medical Center from 1987 through 1989 to assess the occurrence of antibiotic resistance in patients of different ages. Of 325 total strains isolated, 24% produced beta-lactamase, rendering them resistant to ampicillin and amoxicillin. Antibiotic resistance was as common in patients older than age 60 (24%) as in younger patients (23%). Sensitivity testing by disk diffusion and microdilution techniques on 71 isolates (37 beta-lactamase-positive) showed uniform susceptibility to cefuroxime, cefotaxime, amoxicillin/clavulanate, cefaclor, and chloramphenicol, but three beta-lactamase-positive isolates were resistant to trimethoprim/sulfamethoxazole. The high rate of ampicillin resistance noted in elderly patients has implications for the choice of antimicrobial therapy for these infections.

Adolescent↗
PubMed1997

Serious dermatologic reactions in children.

Although serious reactions comprise only a small percentage of total adverse drug reactions, they are important in terms of morbidity and potential mortality. An update on serious dermatologic reactions in children is presented including serum sickness-like reactions due to cefaclor, hypersensitivity syndrome reactions (HSRs), and drug-induced pseudoporphyria. More detailed information on minocycline-induced reactions including drug-induced lupus and HSRs and lamotrigine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome will be discussed.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Drainage of liver abscess via laparoscopic trocar with local anesthesia.

There are several methods for treatment of liver abscess. These include drainage by open surgery, laparoscopic surgery, or percutaneous catheterization. In this report a new therapeutic approach is presented. A 47-year-old man admitted to the hospital had an abscess 12 cm in diameter, originating from the left liver lobe. After the patient's permission was obtained, a laparoscopic trocar was inserted into the abscess with the patient under local anesthesia in the operating room. A 28-French chest tube catheter was introduced through the trocar cannula, and approximately 1,000 mL of pus was drained. There were no complications, and the patient was discharged on the same day. After computed tomography showed an obliterated abscess cavity, the drain was removed on postoperative day 7. The pus culture, performed on the day of surgery, was found to be positive for Escherichia coli, which was responsive to cefaclor. Oral antibiotic therapy was given for 1 month. At follow-up 2 months after surgery, the patient was asymptomatic. This report describes the first case of a liver abscess drained by a laparoscopic trocar with local anesthesia. This method can be the treatment of choice for some easily accessible liver abscesses.

Anesthesia, Local↗
PubMed2002

Immunoglobulin E binding determinants on beta-lactam drugs.

PURPOSE OF REVIEW: Allergies to penicillins and cephalosporins remain an important clinical problem, but structural and immunochemical knowledge of the allergenic structures involved has tended to lag behind the heavy usage, consequent adverse reactions and introduction of new therapeutic members of these two families of antibiotics. Evidence of the increasing incidence of reactions to cephalosporins and to "minor" determinants of the beta-lactams is accumulating. Also, although numerous reports detail unique allergic recognitions of individual members of the two families, particularly the cephalosporins, information remains predominantly clinical. The present review summarizes the most recent advances in studies of structural aspects of beta-lactams as allergens. RECENT FINDINGS: For the cephalosporins, a pyrazinone allergenic degradation product of cefaclor and cephalexin has been identified and characterized. The widely used cephalosporin cephalothin was shown to cross-react allergenically with benzylpenicillin and the common cross-reacting structure was identified. The fine structural features on the amoxicillin molecule recognized by antibodies that distinguish "major" and "minor" determinants were identified, and steric factors were used to explain antibody recognition of the amoxicillin determinants. A recent study elucidated the molecular basis of some cases of the multiple drug allergy syndrome and its relationship to beta-lactam allergy. SUMMARY: Findings of the type described in the present review provide fundamental insights into the nature and size of antigenic determinants on "small" molecules such as drugs and other chemicals. At the clinical level, such structure/activity findings have implications for our understanding of drug allergenic cross-reactions, for selection for therapy of an appropriate member from a family of structurally related drugs and, ultimately, for desensitization of drug-allergic patients.

Allergens↗