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PubMed2005

Trends in antibiotic resistance of respiratory tract pathogens in children in Geneva, Switzerland.

UNLABELLED: Bacteria increasingly resistant to antibiotics are a major treatment concern of respiratory tract pathogens in children. The aim of this study was to assess the trends of resistance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to several classes of antibiotics in children<16 years of age and to compare its prevalence with surrounding countries. We studied retrospectively the susceptibility of respiratory tract pathogens isolated from specimens collected from patients at the Geneva Children's Hospital between 1989 and 2004. The susceptibility of S. pneumoniae to penicillin decreased from 98% to 58% (P<0.001) within 16 years, mainly due to strains intermediately resistant (MICs 0.12-1.0 microg/ml). Also erythromycin-susceptible pneumococci decreased from 97% to 63% (P<0.001). The susceptibility of H. influenzae to amoxicillin also significantly declined (87% vs. 82%, P<0.001), and the susceptibility of M. catarrhalis to this drug almost disappeared (29% vs. 5%, P<0.001). However, in 2004 these two bacteria remained 100% susceptible to amoxicillin-clavulanic acid, second and third generation cephalosporins. Invasive H. influenzae strains were significantly more resistant to ampicillin than non-invasive strains, but no susceptibility difference between invasive and non-invasive S. pneumoniae was determined. CONCLUSION: During the 16 years studied, the antibiotic resistance of respiratory tract pathogens steadily and significantly increased in children, especially S. pneumoniae. This situation in Geneva is similar to neighbouring France rather than to the rest of Switzerland. A permanent surveillance of microbial susceptibility to antibiotics is essential and a limitation of antibiotic prescription together with information of the judicious use may impede the actual resistance trend.

Child↗

PubMed2002

[beta-lactam-antibiotics in the treatment of community-acquired respiratory tract infections with penicillin-resistant pneumococci].

Streptococcus pneumoniae is still the most important pathogen of community-acquired respiratory tract infections. During the last decades in many countries an increase in the spread of antibiotic resistant strains (e. g. against beta-lactams, macrolides, tetracyclin) was observed. Resistance against penicillin is often associated with resistance against macrolides and other antibiotic classes. In Germany surveillance studies including isolates from patients with community-acquired respiratory tract infections have shown that about 14 % of strains show a reduced susceptibility against penicillin (MIC-values 0.12 - 1 mg/L) and up to 4 % are highly resistant against penicillin (MIC >/= 2 mg/L). Resistance against tetracycline or macrolides was detected in up to 12 and 15 % of strains, respectively. According to the treatment guidelines of the Paul-Ehrlich-Gesellschaft für Chemotherapie and the Deutschen Atemwegsliga penicillins and cephalosporins are recommended as first line antibiotics for the treatment of community-acquired respiratory tract infections. As pneumococcal strains with reduced susceptibility against penicillin show often also a reduced susceptibility against cephalosporins the questions arises which beta-lactam antibiotics should still be used in empirical treatment of such strains. beta-Lactam-antibiotics highly differ in their in-vitro-activity against S. pneumoniae and their pharmacokinetic properties. In different models is has been demonstrated for beta-lactams that an adequate clinical and bacteriological efficacy is achievable when the serum levels of the free, i. e. not protein bound fraction of drug exceeds the MIC of the pathogen for at least 40 to 50 % of the dosing interval (T > MIC). In a clinical situation where pneumococci with reduced susceptibility against penicillin cannot be ruled out, only beta-lactam antibiotics with favourable pharmacological properties (good in-vitro activity, high and long lasting serum levels) should be used for treatment.

Anti-Bacterial Agents↗

PubMed2001

Compilation and meta-analysis of randomized placebo-controlled clinical trials on the prevention of respiratory tract infections in children using immunostimulants.

BACKGROUND: Several immunostimulants presume to prevent respiratory tract infections (RTIs) in children, but their efficacy is controversial. OBJECTIVES: To compile the findings of the randomized, placebo-controlled trials (RCTs) on the prevention of acute respiratory tract infections (ARTIs) in children using immunostimulants, and to perform a meta-analysis. DATA SOURCES: Medline, EMBASE databases, and register of Cochrane Acute Respiratory Infection Group. REVIEW METHODS: We searched all the references of immunostimulants and selected papers referring to RCTs on the prevention of ARTIs in children. Papers were rated according to Jadad's instrument. We abstracted the number of ARTIs, and a one-tailed probability value (p) was abstracted for each trial. Effect of medication was determined as weighted mean +/- SE of percent reduction of ARTIs regarding ARTIs of placebo groups as 100%. RESULTS: Four of five RCTs with Jadad's score > 3 showed significant reduction of ARTIs in immunostimulant groups. When only the trials reporting mean +/- SD and/or dispersion were considered (n = 16), the global weighted percent effect of immunostimulants showed a change of -42.64%, with 95% confidence intervals from -45.19% to -40.08%; i. e., the treated group presented about 60% of the mean number of ARTIs in the placebo group. CONCLUSIONS: According to this meta-analysis and RCTs with Jadad's score > 3, immunostimulants are an effective treatment for the prevention of ARTI. Further high-quality RCTs are required to demonstrate the effect and the size of the effect of each individual immunostimulant.

Adjuvants, Immunologic↗

PubMed1991

Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen.

The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation.

Administration, Topical↗

PubMed2004

Respiratory tract infections in Greenland: results of an audit project.

OBJECTIVES: To elucidate and improve quality of diagnosis and treatment of respiratory tract infections in Greenland. STUDY DESIGN: All district medical officers and nursing staff in the Greenlandic coastal health services were invited to participate in the study. Twenty-five district medical officers and the nursing staff from nine districts completed the project and registered in a 3-week period 1,163 contacts involving respiratory tract infections. METHODS: Self-registration according to the Audit Project Odense (APO) method on a simple APO registration chart. All contacts involving respiratory tract infections were registered with regard to sex, type of contact, contact form, infection focus, diagnosis and treatment, origin of infection, antibiotic treatment, choice of antibiotics and possible sick-leave. RESULTS: Of the 1,163 registered contacts lung infections represented 26%, throat infections 22% and otitis media 16%. Paraclinical tests were performed in 32% of the cases, 47% of the cases were treated with antibiotics, in 2/3 of the cases with penicillin V. The use of paraclinical tests was somewhat lower and the use of antibiotics was higher than in Denmark. CONCLUSION: The study showed that it is possible to carry out an APO audit in Greenland, and that there was a moderate difference in the diagnosis and treatment between Greenland and Denmark. An increased use of paraclinical tests may result in quality improvement.

Anti-Bacterial Agents↗

PubMed2004

Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice.

Following intranasal administration, the severe acute respiratory syndrome (SARS) coronavirus replicated to high titers in the respiratory tracts of BALB/c mice. Peak replication was seen in the absence of disease on day 1 or 2, depending on the dose administered, and the virus was cleared within a week. Viral antigen and nucleic acid were detected in bronchiolar epithelial cells during peak viral replication. Mice developed a neutralizing antibody response and were protected from reinfection 28 days following primary infection. Passive transfer of immune serum to naïve mice prevented virus replication in the lower respiratory tract following intranasal challenge. Thus, antibodies, acting alone, can prevent replication of the SARS coronavirus in the lung, a promising observation for the development of vaccines, immunotherapy, and immunoprophylaxis regimens.

Animals↗

PubMedDate not supplied

Epidemiologic risk factors for children with acute lower respiratory tract infection in Buenos Aires, Argentina: a matched case-control study.

The risk factors that predisposed 516 hospitalized and 154 ambulatory patients to acute lower respiratory tract infection (ALRI) are examined in a matched case-control study. The control group was selected from children attending immunization and well-baby clinics at the same institution that was treating the children with ALRI. Sex, age, nutritional status, socioeconomic level, as well as season and place of residence were used as matching criteria. Because of their distinct profiles, hospitalized and outpatient groups were analyzed separately. However, the four variables with the highest odds ratios (incidence ratios or relative risk) were found to be the same for both groups. These variables were related to the host's condition (bronchial hyperreactivity, presence of persistent symptoms of the upper respiratory tract), family (presence of acute respiratory tract disease in household members), and environment (indoor contaminants).

Acute Disease↗

PubMed1976

Clearance of benzo(a)pyrene from the respiratory tract of hamsters following its intratracheal instillation with or without ferric oxide.

A comparative study was carried out on the clearance of benzo(a)pyrene (BP) from the respiratory tract of Syrian golden hamsters following intratracheal instillation of either BP alone or BP attached to ferric oxide particles. Eight series of 18 hamsters each, received a single intratracheal instillation of 0.5 or 1.0 mg BP suspended in 0.9% NaCl solution. In addition, three comparable series of hamsters received in the same way a mixture, of 1.0 mg BP + 1.0 mg ferric oxide suspended in 0.9% NaCl solution. In each of the series the BP content of the respiratory tract was determined at six different points of time viz. immediately after administration of BP or BP + ferric oxide, and three, six and 24 hours, and three and seven days after an instillation. The clearance of BP from the respiratory tract did not appear to be significantly influenced by the presence of ferric oxide. It was concluded that the present study produced no evidence of ferric oxide particles being capable of enhancing the retention of BP in the respiratory tract.

Animals↗

PubMed1996

Comparison of amoxycillin and clarithromycin as initial treatment of community-acquired lower respiratory tract infections.

BACKGROUND: Numerous new oral antibiotics have been produced over the last few years with the aims of improving treatment for lower respiratory tract infections. AIM: The aim of the study was to compare the efficacy of an established drug, amoxycillin, with a new macrolide, clarithromycin, for initial treatment of adults with community-acquired lower respiratory tract infection. METHOD: Consecutive adults fulfilling a standard definition of lower respiratory tract infection presenting to 14 general practitioners in two neighbouring practices were allocated to antibiotic therapy in a random, single-blind manner. The outcome of treatment was assessed by the time taken by the patient to return to normal activities or work, the speed of resolution of symptoms, number of repeat consultations and side effects. RESULTS: The profile of the 221 patients receiving amoxycillin was very similar to that of the 221 receiving clarithromycin. The two groups did not differ greatly in requirement to visit the general practitioner again within either 4 weeks (20% amoxycillin group; 25% clarithromycin group) or 3 months (31% compared with 36%) of the original infection, in time taken to return to normal activities (6 days for group taking amoxycillin; 5 days for those on clarithromycin) or work (5 days for both groups), or in speed of resolution of symptoms. Compliance was good and the side-effects reported were similar for both groups. No increase in gastrointestinal complaints was noted for patients taking the macrolide. CONCLUSION: Amoxycillin and clarithromycin appear to be equally effective as initial therapy and to be tolerated in similar ways. Use of the newer drug appears to have no advantages over use of the accepted standard treatment.

Adolescent↗

PubMed1996

Restricted B-cell responses to microbial challenge of the respiratory tract.

The local B-cell response in the respiratory tract to infectious challenge has been analyzed in pigs and calves using two techniques: flow cytometry and antibody secreting cell (ASC) probes. Pneumonia in pigs caused by experimental infection with Mycoplasma hyopneumoniae resulted in a 25-fold increase in the B-cell population in BAL and lung parenchyma 28 days post infection. ASC probes revealed that the B-cell response of immune pigs to a large challenge infection was localized to lung parenchyma and tracheobronchal lymph nodes. Naive calves infected with Pasteurella multocida had a 5-fold increase in the B-cell blast population in lung parenchyma and BAL, and a greater than 60-fold increase in the draining lymph node at 9 days post infection. The ASC probes prepared post challenge from immune calves showed the response to be localized to the draining lymph nodes, with little response in lung parenchyma. A major finding was that ASC probes prepared from lung parenchyma and from pulmonary lymph nodes of both calves and pigs recognized a restricted range of bacterial antigens, particularly compared to the range of antigens recognized by concurrently circulating sera. The use of ASC probes demonstrates that there is a restricted B-cell repertoire in the respiratory tract.

Animals↗

PubMed1995

Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract.

Mutations of the p53 tumor suppressor gene are the most common genetic alterations associated with human cancer. Tumor-associated p53 mutations often show characteristic tissue-specific profiles which may infer environmentally induced mutational mechanisms. The p53 mutational frequency and spectrum were determined for 95 carcinomas of the upper and lower respiratory tract (32 lung and 63 upper respiratory tract). Mutations were identified at a frequency of 30% in upper respiratory tract (URT) tumors and 31% in lung tumors. All 29 identified mutations were single-base substitutions. Comparison of the frequency of specific base substitutions between lung and URT showed a striking difference. Transitions occurred at a frequency of 68% in URT, but only 30% in lung. Mutations involving G:C-->A:T transitions, which are commonly reported in gastric and esophageal tumors, were the most frequently identified alteration in URT (11/19). Mutations involving G:C-->T:A transversions, which were relatively common in lung tumors (3/10) and are representative of tobacco smoke-induced mutations were rare in URT tumors (1/19). Interestingly, G:C-->A:T mutations at CpG sites, which are characteristic of endogenous processes, were observed frequently in URT tumors (9/19) but only rarely in lung tumors (1/10), suggesting that both endogenous and exogenous factors are responsible for the observed differences in mutational spectra between the upper and lower respiratory systems.

Alcohol Drinking↗

PubMed2000

Antitussive efficacy of dextromethorphan in cough associated with acute upper respiratory tract infection.

Dextromethorphan is one of the most widely used antitussives for the treatment of cough associated with acute upper respiratory tract infection. However, there is very little data to support the efficacy of dextromethorphan in this disease state. This aim of this study was to obtain more information about the efficacy of a single dose of 30 mg dextromethorphan in the treatment of cough associated with acute upper respiratory tract infection. The study was a double-blind, stratified, randomized and parallel group design. Both objective and subjective measurements of cough were recorded over 10-min recording periods in a quiet room before (baseline) and at 90, 135 and 180 min after treatment. Forty-three patients (30 females and 13 males), mean age 22.9 years (range 18-46 years), with acute dry or slightly productive cough and otherwise healthy were included in the study. Patients were randomized to placebo treatment (n = 22) and dextromethorphan treatment (n=21). The results showed similar trends in both treatment groups with statistically significant reductions (P < 0.05) in cough sound pressure level (CSPL), cough frequency (CF) and subjective scores for cough severity within treatment groups but little difference between the treatment groups during the study period. The only statistically significant difference between treatment groups was for the mean CSPL changes from baseline to 90 min (P=0.019). There was a significant positive correlation between CSPL and CF (r = 0.752, P= 0.000) for changes in cough measurements from baseline to 90 min after treatment and this indicates that CSPL may be a useful measure of cough severity. This study provides very little if any support for clinically significant antitussive activity of a single 30 mg dose of dextromethorphan in patients with cough associated with acute upper respiratory tract infection.

Adolescent↗

PubMed1991

Immunoregulation of asthma: control of T-lymphocyte activation in the respiratory tract.

Allergic asthma results ultimately from inappropriate responses to non-pathogenic airborn antigens by the respiratory tract T-cell system. In order to understand how sensitization to inhaled antigens develops, it is necessary to precisely define the tissue microenvironments within which T-cells occur in the respiratory tract, and to analyse the factor(s) which regulate their local activation. This review focuses upon recent data on the distribution of T-cells and antigen presenting cells within the lung and airway tissues of man and experimental animals, and examines the available information on their responses to antigenic stimulation. We argue that in the steady state, respiratory tract T-cells are tightly regulated by a series of inherent and acquired immunosuppressive control mechanisms, which normally limit local T-cell activation to situations where antigenic exposure is accompanied by an inflammatory stimulus, such as the case with incoming pathogenic microorganisms.

Allergens↗

PubMed1984

Efficacy of ceftizoxime administered twice daily in hospitalized patients with respiratory tract infections.

The efficacy and safety of ceftizoxime administered twice daily were evaluated in 215 hospitalized patients with documented lower respiratory tract infections. The majority of patients received 1 to 2 gm of ceftizoxime intramuscularly or intravenously every 12 hours; the mean dosage was 2 gm/day, and the mean duration of therapy was 8.9 days. Clinical cure was achieved in 204 (95%) of the 215 patients with lower respiratory tract infection. One hundred and thirty-eight patients were both clinically and bacteriologically evaluable. The clinical response rates, by organism, were: Streptococcus pneumoniae, 100% (50/50); Haemophilus influenzae, 96% (25/26); gram-negative bacilli (Escherichia coli, Proteus mirabilis, Enterobacter sp, Serratia sp, Pseudomonas sp, Klebsiella sp, Citrobacter sp, and Morganella morganii), 86% (32/37); and Staphylococcus aureus, 92% (12/13). In the other 77 patients with clinical symptoms, no pathogen was isolated or insufficient follow-up data were collected to assess bacteriologic response. Adverse reactions, which were infrequent, were similar to those reported in other US trials of the drug. The findings indicate that ceftizoxime, 1 to 2 gm BID, is effective and safe in the treatment of lower respiratory tract infections in hospitalized patients. This low-dose regimen can significantly reduce the cost of cephalosporin therapy.

Adolescent↗

PubMedDate not supplied

[Partial removal of the mesenchyma disrupts the growth and differentiation of the epithelium in respiratory tract explants from strain A and C57BL mouse embryos].

Differentiation of respiratory epithelium (E) of 17-day old embryos of A and C57BL mice after partial removal of mesenchyme (M) was studied in organ culture. In control explants, tissue-specific growth and differentiation of epithelium were observed during long-term culturing. Ih both mouse strains, partial removal of mesenchyme prevented the development of alveolar-like structures in explants of distal part of respiratory tract. In most explants of proximal part of respiratory tract (65.1% in A mice and 85.7% in C57BL mice) with partially removed mesenchyme, we found atypical epithelial structures and foci of poorly differentiated cells with high proliferation rate.

Animals↗

PubMed2005

Antimicrobial activity of tigecycline tested against organisms causing community-acquired respiratory tract infection and nosocomial pneumonia.

Emerging antimicrobial resistance among respiratory tract pathogens has created a critical need for development of new antimicrobial agents that are not affected by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel broad-spectrum parenteral glycylcycline, has been shown to be active against many of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including strains highly resistant to commonly prescribed antimicrobials and was recently approved by the US Food and Drug Administration for treating infections of skin and skin structures, and for intra-abdominal infections. In this study, tigecycline spectrum and potency were evaluated against a global collection of pathogens (2000-2004) recovered from community-acquired respiratory infections (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among community-acquired infections, the ranking pathogens were Haemophilus influenzae (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7% penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline displayed potent activity by inhibiting 100% of the 3 species at clinically achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%), and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL, tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S. aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5 microg/mL, respectively) with all strains inhibited at < or =1 microg/mL. Streptococci recovered from hospitalized patients (beta-hemolytic and S. pneumoniae) were also very susceptible to tigecycline with the highest MIC being 0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta-lactamase [ESBL] phenotype) were inhibited by < or =1 microg/mL, and all Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4 microg/mL, respectively). Further clinical studies should consider the role that tigecycline may play in the therapy for severe respiratory tract infections, both of nosocomial and community origin.

Anti-Bacterial Agents↗

PubMedDate not supplied

Escherichia coli multiplication and lesions in the respiratory tract of chickens inoculated with infectious bronchitis virus and/or E. coli.

Escherichia coli numbers and histopathological changes were studied in the respiratory tract of line 151 chickens intranasally inoculated with infectious bronchitis virus (IBV) and/or virulent E. coli; this line is highly susceptible to IBV. Chickens inoculated with IBV alone showed increased numbers of E. coli in the trachea and had tracheitis, airsacculitis, and bronchiolitis. One of 17 chickens inoculated with IBV alone died with fibrinopurulent serositis. Chickens inoculated with IBV and E. coli had more severe and persistent respiratory lesions than those inoculated with IBV alone. E. coli was isolated from tracheas of chickens inoculated with IBV and E. coli more frequently than from chickens inoculated with IBV alone. In this group, 14 of 27 chickens died with tracheal plugs or with fibrinopurulent serositis. There was neither increased numbers of E. coli nor significant lesions in the respiratory tract of the group inoculated with E. coli alone. These results suggest that IBV may facilitate E. coli invasion into the lower respiratory tract of the chicken.

Animals↗

PubMed2005

Prescription rates and diagnostic patterns are stable: a comparison of high-, medium- and low-prescribing primary care physicians treating community-acquired respiratory tract infections.

The objective was to study prescription practices of primary care physicians in prescribing antibiotics for community-acquired respiratory tract infections. Design was time series analysis and cross-sectional survey. The setting was 30 community primary health care centres. A case report form was completed for 3478 patient consultations treated by 198 office-based primary care physicians. Main outcome measures were: classification of diagnoses of respiratory tract infections made by each physician; number of antibiotic prescriptions related to these diagnoses; each physician's mean weekly number of antibiotic prescriptions during 6 months before and after the survey. Patients' risk (odds ratio: OR) to receive an antibiotic prescription from the high and medium prescribers was 5.81 (95% confidence interval [CI] 4.85-6.96) and 2.41 (95% CI 2.04-2.86), compared to low prescribers. High and medium prescribers made more diagnoses of otitis media (OR 2.07, 95% CI 1.70-2.53 and 1.85, 95% CI 1.51-2.26, respectively) and fewer diagnoses of unspecified upper respiratory tract infection (OR 0.32, 95% CI 0.26-0.38 and 0.57, 95% CI 0.48-0.68, respectively) than low prescribers. The rank of the prescription rate of high, medium and low prescriber groups remained the same for all diagnoses except pneumonia. In addition, the annual rank between high, medium and low prescriber groups remained stable; high group prescribed more antibiotics during the year than medium group, which prescribed more than low prescriber group.

Anti-Bacterial Agents↗