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Antibiotic susceptibility of Streptococcus pneumoniae in Karachi.

OBJECTIVE: To evaluate, record and analyse the comparative activity of a range of oral antibiotics against Streptococcus pneumoniae. SETTING: Specimen collected at a private laboratory and some received from different hospitals and clinics. MATERIALS: The specimen comprised of Sputum, Throat Swabs, C.S.F., Pus, Pleural fluid, Ear Swabs, Eye Swabs, Bronchial Wash, Prostatic discharge and Antral Secretions. METHODS: The isolates were tested for their antibiotic susceptibility using the E-test by the methods described in the study protocol. The groups of antibiotics tested were Amoxicillin--Clavulanate, Clarithromycin, Cefaclor, Cefuroxime, Ceftriaxone and Penicillin. RESULTS: A total of 116 strains of Streptococcus pneumoniae were isolated and susceptibility to Amoxicillin-Clavulanate was 100%, 99.1% strains were susceptible to Cefuroxime and 0.9% were intermediate. Susceptibility to Penicillin was 80.2% and 19.8% of the strains were in intermediate category, while susceptibility to Clarithromycin was 89.7%, 1.7% were in intermediate region and 8.6% of the strains were resistant to this antibiotic. The susceptibility pattern of Cefaclor was not calculated as there is no current NCCLS--97 Cefaclor breakpoints available. CONCLUSION: The percentage of drug resistant Streptococcus pneumoniae was negligible in Karachi during the study period, however it is important to monitor the susceptibility pattern to keep a check on an increase in the number of DRSP as reported at different centres in Turkey, Saudi Arabia, Singapore, Thailand, Hong Kong and Indonesia.

Anti-Bacterial Agents↗

[Antibiotic resistance and serotype distribution of Streptococcus pneumoniae strains isolated from patients at Hacettepe University Medical Faculty].

The emergence of penicillin and multidrug resistant pneumococci has become a global concern. In this study, the in-vitro susceptibilities of 212 Streptococcus pneumoniae strains, isolated from different clinical specimens, to penicillin, erythromycin, cefaclor, cefotaxime, vancomycin, rifampin, tetracycline, chloramphenicol and ciprofloxacine were tested by agar dilution method. Penicillin resistance and intermediate penicillin resistance were found in 7.08% and 41.51% of isolates, respectively. Overall percentages of resistance to erythromycin, cefaclor, cefotaxime, rifampin, tetracycline, chloramphenicol and ciprofloxacine were 13.7%, 17.5%, 2.3%, 2.1%, 18.9%, 2.3% and 1%, respectively. Vancomycin resistance was not detected in the tested strains. All penicillin-susceptible S. pneumoniae isolates were also found to be susceptible to cefaclor, cefotaxime, chloramphenicol and ciprofloxacine. Resistance to other antimicrobial agents was higher among the penicillin-resistant group than the penicillin-susceptible one. Although high level penicillin resistance rate was low, 41.51% of pneumococci were intermediately resistant to penicillin. These results indicated that penicillin resistant S. pneumoniae isolates might probably become a major problem in the near future. Serotyping of penicillin intermediate and resistant S. pneumoniae isolates (n:103) by the capsular swelling test (Quellung reaction) revealed serotypes 19 (n:21), 23 (n:17), 9 (n:8), 14 (n:5), 6 (n:5), 3 (n:4), 15 (n:3), 8 (n:2), 1 (n:2), 20 (n:2) and serotypes 5, 10, 33, 22, 7 and 4 as single isolates. Twenty six S. pneumoniae isolates failed to be serotyped by the antisera set used. All serotype 9 pneumococci strains were found to be multidrug-resistant. Other multidrug-resistant pneumococci strains belonged to serotypes 19, 23 and nontypable group. The serotypes detected among the penicillin intermediate and resistant pneumococci in our study, are among the serotypes covered by 23-valent and 7-valent conjugated pneumococcal vaccine, indicating the possible preventive role of the vaccine against drug-resistant pneumococcal infections.

Anti-Bacterial Agents↗

[Resistance surveillance of common community respiratory pathogens isolated in China, 2002 - 2003].

OBJECTIVE: To investigate antimicrobial resistance of common community respiratory pathogens isolated in China, 2002 - 2003. METHODS: 779 strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Group A beta-haemolytic Streptococci and oxacillin-susceptible Staphylococcus aureus (MSSA) were isolated from patients with community-acquired respiratory tract infections at 5 hospitals in China from April 2002 to 2003. Meanwhile, 185 strains of S. pneumoniae, H. influenzae and M. catarrhalis were isolated from nasopharynx swabs at 2 day-care centers in Beijing. Agar dilution method was used to determine the minimal inhibitory concentration (MICs) of cefprozil and other 9 antibiotics against these strains. RESULTS: The prevalence of penicillin-intermediate S. pneumoniae (PISP) was 23.9% and that of penicillin-resistant S. pneumoniae (PRSP) was 22.7% at 5 cities in China. The prevalence of PISP were 44.1% in Hangzhou, 26.2% in Wuhan, 21.5% in Shenyang, 20.8% in Shanghai, 18.5% in Beijing, and 12.7% at day-care centers in Beijing;the prevalance of PRSP were 34.9% in day-care centers, 31.9% in Shanghai, 27.9% in Wuhan, 22.1% in Hangzhou, 13.8% in Shenyang and 8.6% in Beijing. The susceptible rate of levofloxacin in S. pneumoniae was 96.3%. 9.5% of H. influenzae and 87.4% of M. catarrhalis produced beta-lactamases. The susceptibility of amoxicillin/clavulanate, cefaclor, cefprozil, cefuroxime, ceftriaxone, azithromycin, and levofloxain in these two species ranged from 96.4% to 100%. The resistance rate of azithromycin in S. pneumoniae was higher than 60%. Cefprozil MICs against PISP, Group A beta-haemolytic Streptococci and MSSA were 4 - 16 fold lower than cefaclor. CONCLUSIONS: Antimicrobial resistance in respiratory pathogens, especially S. pneumoniae is increasing. It brings concerns that high macrolide resistance was found in gram-positive cocci. Cefprozil was more active than cefaclor against respiratory pathogens.

Anti-Bacterial Agents↗

[Comparison of in vitro activity of 4 oral beta-lactams on microorganisms responsible for broncho-pulmonary infections in children].

MIC 90 and MBC 90 of amoxicillin, cefaclor, cefadroxil and cefuroxime axetil have been determined by the microdilution method against 48 organisms responsible of acute respiratory tract infections in children: 17 E. coli, 15 K. pneumoniae, 16 H. influenzae. An inoculum effect and an inhibitory index in blood and bronchial secretions were determined. An inoculum effect was more important for amoxicillin and cefadroxil than for cefuroxime axetil and cefaclor. Against H. influenzae, cefuroxime axetil and cefaclor have a similar activity. Against Enterobacteria, cefuroxime axetil has the lowest MIC 90 and MBC 90 and the highest inhibitory index.

Administration, Oral↗

Cefpodoxime proxetil, its in vitro antibacterial activity, affinity to bacterial penicillin-binding proteins, and synergy of bactericidal activity with serum complement and mouse-cultured macrophages.

Cefpodoxime proxetil (CS-807) is an orally active prodrug of an oxime-type cephem antibiotic. The MIC60 values of cefpodoxime (R-3746) the active form of CS-807, were 3.13, 6.25, 0.05, 0.38, 0.2, 0.1, 3.13, 3.13, 6.25, 6.25, 0.1 and 12.5 micrograms/ml against S. aureus, coagulase-negative staphylococci, S. pneumoniae, E. coli carrying R plasmids, P. vulgaris, P. rettgeri, C. freundii, S. marcescens, A. calcoaceticus, P. cepacia, ampicillin-resistant H. influenzae and B. fragilis, respectively. Its activity was stronger than that of cefaclor and ampicillin. R-3746 manifested little activity against P. aeruginosa, methicillin-resistant S. aureus, and Enterococcus spp. R-3746 showed stronger binding affinity than cefaclor with the PBP2 of S. aureus, PBPs 1a, 1bs, 2 and 3 of E. coli, PBPs 1b, 1c and 3 of P. rettgeri, and the PBP3 of P. aeruginosa than cefaclor. Synergy of the bactericidal effect between R-3746 and serum complement was moderate, although the cells of E. coli NIHJ-JC2 and S. aureus 209P were well engulfed and rapidly digested by mouse-cultured macrophages in the presence of greater than 1/8 MIC of R-3746. Good clinical efficacy can be expected of CS-807 provided its pharmacokinetics prove to be good.

Bacteria↗

Interaction of cefdinir with beta-lactamases.

The interactions of cefdinir, a new orally-active third-generation cephalosporin, with cell-free beta-lactamase preparations were studied in comparison with some other beta-lactams. Cefdinir was very resistant to narrow-spectrum Ambler's class A beta-lactamases, as it was for other oximino beta-lactams: cefotaxime, ceftazidime, cefixime and cefuroxime. Cefaclor showed a low but significant hydrolysis by these beta-lactamases. These class-A enzymes include the widespread plasmid mediated TEM-1, TEM-2, SHV-1 and also the enzymes of Gram-positive penicillinases, such as that produced by S. aureus. The hydrolysis of cefdinir was hardly detectable by the Ambler's class C beta-lactamases (cephalosporinases) produced by E. coli, E. cloacae and M. morganii. A similar conclusion is shown for cefotaxime, ceftazidime, cefixime and cefuroxime: for these beta-lactamases, the hydrolysis of cefaclor was high. The P. vulgaris cephalosporinase differs from the previous cephalosporinases in that it hydrolyses cefotaxime, cefuroxime and cefaclor efficiently. However, the hydrolysis of cefdinir remains too low to be detected. Cefdinir, as other third-generation cephalosporins, showed some hydrolysis by the novel extended-spectrum beta-lactamases (ESBL): SHV-2, TEM-3, TEM-5, MEN-1 and other ESBL.

Bacteria↗

[The antibiotic treatment of respiratory infections in a pediatric emergency room].

Eight years after the first study published in this Journal (1985, 7: 533), we compared antibiotic treatment of respiratory infections at the Pediatric Emergency Department of the Children's Hospital in Trieste. All patients with pneumonia and pertussis received antibiotics, compared to 87% of otitis, 55% of pharyngo-tonsillitis, 4% of upper respiratory infections (U.R.I.); neither asthma nor laryngitis were treated with antibiotics. In particular, only 13% of otitis were treated by symptomatics, the others with amoxicillin (51%), amoxicillin + clavulanic acid (18%), cefaclor (12%), trimethoprim-sulphamethoxazole (5%), josamycin (1%). 45% of pharyngo-tonsillitis was treated with symptomatics, 32% with macrolides and 10% with penicillin; rarer treatment comprehended amoxicillin, amoxicillin + clavulanic acid (10%) and cefaclor (3%). Pneumonia was treated with amoxicillin or cefaclor (30% both), with amoxicillin + clavulanic acid (10%) or with macrolides (30%), the last in provision of mycoplasmal etiology. Antibiotic treatment of U.R.I. is progressively decreased from 79% in 1974 to 13% in 1983 and to 4% in 1991. Antibiotic treatment in our Department was appropriate in the majority of patients, with almost all bacterial form treated with first choice, cheaper antibiotic. A negative, limited trend was detected for pharyngo-tonsillitis: first choice antibiotics passed from 82% in 1983 to 76% in 1991. Another positive factor is due to the homogeneous manners of the doctors working at the Emergency Department, belonging to two different teams (Emergency and Clinical Departments), probably with the use of common clinical protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Influence of cephalosporins on intestinal enzymatic activity.

The effect of the broad spectrum antibiotics cefaclor, cefadroxil, cephradine, cefatrizine, cephaloglycine and cefroxadine was examined on rat intestinal brush border enzymes, aminopeptidase N (E.C. 3.4.11-2), dipeptidyl peptidase IV (E.C. 3.4.14.5) and alkaline phosphatase (E.C. 1.3.1.3.). All the cephalosporins assayed -except cefaclor- inhibit the aminopeptidase N activity, in an uncompetitive manner. Cefatrizine showed the most important inhibitory effect (52.5%; p < 0.001). Cefaclor and cefadroxil have no effect on the activity of the dipeptidyl peptidase IV, while cephaloglycine and cephradine showed a non competitive type inhibition. In contrast, cefatrizine and cefroxadine showed a competitive inhibition for this enzyme. None of the cephalosporins assayed had any effect on alkaline phosphatase activity.

Administration, Oral↗

[In vitro activity of oral cephalosporins (author's transl)].

The in vitro activity of cephradine, cephalexin, and cefaclor was studied in comparison with that of cephalothin. Cefaclor inhibits peptidoglycan synthesis somewhat more than cephalexin and cephradine. There is no marked difference in the stability of the three substances in the presence of beta-lactamases, and the outer membrane of Escherichia coli is no barrier to permeation of any of the three antibiotics.

Bacteria↗

Distribution and resistance patterns of Haemophilus influenzae: a European cooperative study.

The first European survey of the prevalence of antibiotic resistance in Haemophilus influenzae was conducted between February and October 1986. Eighty laboratories in nine countries participated (Austria, Belgium, France, FRG, The Netherlands, Spain, Sweden, Switzerland and the UK). A total of 1,961 clinical isolates was examined for type b encapsulation, beta-lactamase production and susceptibility to ampicillin, chloramphenicol, cefaclor, erythromycin and tetracycline, using a unique microdilution method. The proportion of isolates resistant to these antibiotics varied considerably between individual countries. The highest prevalence of ampicillin resistance was found in Spain (30.6%), and the lowest in the FRG (1.6%), with a mean value of 10% for all countries. Chloramphenicol resistance was highest in Spain (24.9%) and Belgium (10.9%) and lowest in The Netherlands (0.6%) and Austria (0.5%), with a mean value of 4.7%. Resistance to erythromycin ranged from 27% of the isolates in The Netherlands to 1.1% in Austria. For tetracycline, values ranged from 1.5% in the UK to 17.8% in Belgium and 25.4% in Spain. The lowest mean prevalence of resistance was observed for cefaclor (breakpoint 8 mg/l): 5% or less in all countries. These inter-country differences could only partially be explained by variations in the proportion of type b strains, the source of the isolates and the mode of collection.

Ampicillin Resistance↗

The Second European Collaborative Study on the frequency of antimicrobial resistance in Haemophilus influenzae.

In the second European survey of the prevalence of antimicrobial resistance in Haemophilus influenzae, 2529 clinical isolates collected in 1988/89 from 78 laboratories in nine countries (Austria, Belgium, Federal Republic of Germany, France, Italy, The Netherlands, Spain, Switzerland, United Kingdom) were examined. Of these, 23.8% were type b strains. The overall rate of beta-lactamase production was 9.1%, being slightly higher in type b isolates (10.5%) compared to non-type b isolates (8.6%). The MICs of six antimicrobials (ampicillin, cefaclor, chloramphenicol, erythromycin, tetracycline, and cotrimoxazole) were determined by an agar dilution procedure at a single central laboratory. The proportion of isolates resistant to the antimicrobials varied considerably amongst the individual countries. The highest incidence of resistance to all six drugs was observed in strains collected in Spain, whereas resistance was rarely encountered among strains isolated in Austria and the FRG. Resistance to ampicillin (MIC greater than or equal to 4 mg/l) among strains that lacked beta-lactamase activity was uncommon (0.3%). Based on the NCCLS Haemophilus influenzae breakpoints, the rates of susceptibility and resistance to cefaclor, chloramphenicol, tetracycline, and cotrimoxazole were 96.4/1.5, 96.2/2.8, 92.4/4.7, and 87.9/7.3%, respectively. The rate of susceptibility and resistance to erythromycin was 2.3/19.9. Multiple resistance to ampicillin, chloramphenicol, tetracycline, and cotrimoxazole was observed in 15 isolates (0.6%), and resistance to three drugs simultaneously in 72 (1.5%). The incidence of beta-lactamase producing strains was similar to that seen in the first European study performed in 1986 (9.1% vs. 10.9%), and was half that observed in US isolates collected in 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin Resistance↗

Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children.

We investigated the clinical value of intranasal budesonide in acute sinusitis in 52 children with acute maxillary sinusitis. We randomly divided them into two groups: group 1 received oral pseudoephedrine (2 x 30 mg) and cefaclor (40 mg/kg) for 10 days, and group 2 received intranasal budesonide (2 x 100 microg) and cefaclor (40 mg/kg) for 10 days. Symptoms of headache, cough, and nasal stuffiness and signs of nasal discharge were graded before and after treatment. The patients whose symptoms and signs completely normalized after treatment were considered to have recovered, and those with persisting symptoms and signs after treatment as having not recovered. The results of the two treatment groups were compared. The recovery rate of the children in group 2 were significantly higher than those in group 1 (P < 0.05). No adverse drug effects were determined during the study period. These findings suggest that topical steroids may be a useful adjunctive agent in the treatment of acute sinusitis of children without apparent side effects and can possibly hasten the resolution of symptoms.

Acute Disease↗

Emergence and persistence of beta-lactamase-producing bacteria in the upper respiratory tract in children treated with beta-lactam antibiotics.

PURPOSE: To assess the ecologic impact, in terms of selection of beta-lactamase-producing respiratory tract bacteria, of a single course of peroral beta-lactam antibiotics. PATIENTS AND METHODS: One-hundred fifty consecutive children with clinical signs of bacterial respiratory tract infection were randomly assigned to a seven-day course of treatment with either penicillin V, amoxicillin, or cefaclor. Bacteriologic specimens were collected before treatment, at its termination, and at follow-up four weeks later. RESULTS: All three drugs investigated caused a similar increase in beta-lactamase-producing bacteria, both in absolute and relative terms, an increase that persisted over a period of at least one month after completion of treatment. CONCLUSION: Penicillin V, amoxicillin, and cefaclor all act as selective agents for beta-lactamase-producing bacteria in the upper respiratory tract. Treatment with a peroral beta-lactam antibiotic puts patients at risk of becoming persistent carriers of beta-lactamase-producing bacteria.

Amoxicillin↗

In vitro evaluation of cefixime (FK027, FR17027, CL284635): spectrum against recent clinical isolates, comparative antimicrobial activity, beta-lactamase stability, and preliminary susceptibility testing criteria.

Cefixime, a new orally absorbed cephalosporin, was compared by in vitro testing with other oral beta-lactams, including cephalexin, cefaclor, cefuroxime, amoxicillin, and amoxicillin + clavulanate. Enterobacteriaceae were inhibited by lower concentrations of cefixime than any of the reference drugs; 90% and 95% were inhibited by less than or equal to 1.0 and less than or equal to 8.0 micrograms/ml, respectively. Cefixime was the least active among these drugs against staphylococci, with only 31% of 1106 strains inhibited by less than or equal to 8.0 micrograms/ml and less than 1% by less than or equal to 1.0 microgram/ml. Enterococci and pseudomonads were not susceptible to any of the drugs tested. Penicillin-resistant pneumococci were relatively resistant to cefixime, but penicillin-susceptible pneumococci were very susceptible to cefixime. Other streptococci were generally susceptible to all compounds tested, with relative activities of amoxicillin greater than cefaclor and cefuroxime greater than cefixime greater than cephalexin. Cefixime was inactive against Bacteroides species. A slight inoculum effect occurred with cefixime with inocolum concentrations varying from 10(5) to 10(6) colony forming units per milliliter, but this was more marked at 10(7) colony forming units per milliliter. Cefixime was resistant to hydrolysis by seven common beta-lactamases. It inhibited the hydrolysis of nitrocefin only by type 1 cephalosporinases. The disk diffusion zone diameter breakpoints for the 30-micrograms cefixime disk were determined by regression analysis to be greater than or equal to 27 mm (susceptible) and less than or equal to 23 mm (resistant), respectively corresponding to minimal inhibitory concentration breakpoints of less than or equal to 1.0 and greater than or equal to 4.0 micrograms/ml. Because of the high interpretive error rate (13.8%) and the occurrence of these breakpoints on the parabolic portion of the regression curve, we recommend further evaluation of cefixime disks with lower potencies.

Amoxicillin↗

Prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae: a collaborative study.

The prevalence of antimicrobial resistance was assessed among a total of 3,356 clinical isolates of Haemophilus influenzae obtained from 22 medical centers distributed throughout the United States during the period July, 1983 through June, 1984. All strains were examined for beta-lactamase production with a rapid acidometric assay and for resistance to ampicillin, chloramphenicol, cephalothin, cefamandole, cefaclor, tetracycline, and erythromycin with a standardized disk diffusion procedure. The overall rate of beta-lactamase production was 15.2%, although results of disk diffusion tests suggested that the overall rate of ampicillin resistance was 19.5%. Twenty-one percent of encapsulated type b strains produced beta-lactamase; 12.1% of non-type b strains were beta-lactamase positive. Specific rates of beta-lactamase production obtained at individual study centers varied widely with no evidence of geographic clustering. The highest rates of beta-lactamase production were observed with isolates of H. influenzae recovered from infants and young children, and from blood and cerebrospinal fluid specimens. The overall rate of chloramphenicol resistance was 0.6%. The prevalence of cephalothin, cefamandole, cefaclor, tetracycline, and erythromycin resistance was 9.9%, 2.4%, 2.8%, 6.4%, and 64.2%, respectively. beta-Lactamase positive isolates of H. influenzae had higher rates of resistance to all of the cephalosporins than did strains that lacked beta-lactamase.

Adolescent↗

Comparative antimicrobial spectrum and activity of ceftibuten against clinical isolates from West Germany.

The in vitro activity of a new oral cephalosporin, ceftibuten, was determined against 837 clinical isolates by agar dilution technique and compared with that of the oral cephalosporins, cefaclor, cefuroxime, cefixime, cefpodoxime, and cefprozil. Against Enterobacteriaceae, ceftibuten was the most active of the compounds. Ceftibuten MIC90s were less than or equal to 0.25 micrograms/ml for most members of the family Enterobacteriaceae, 0.13 microgram/ml for Haemophilus influenzae, 4 micrograms/ml for Moraxella catarrhalis, and 0.5 microgram/ml for Neisseria gonorrhoeae. Ceftibuten also was active against beta-haemolytic streptococci (serogroups A, C, and G) and penicillin-susceptible strains of Streptococcus pneumoniae (MIC90, 4 micrograms/ml), but was not active against Staphylococcus spp. or the anaerobic bacteria studied. Cefpodoxime and cefuroxime were the most active of the cephalosporins against nonenteric streptococci; cefprozil and cefuroxime were the most active against staphylococci, and cefaclor demonstrated the greatest activity against some Bacteroides spp. Most strains of Acinetobacter baumanii, Pseudomonas spp., and methicillin-resistant staphylococci, as well as all strains of Clostridium difficile, were resistant to each of the cephalosporins tested.

Anti-Infective Agents, Urinary↗

In vitro activity of ceftibuten against Haemophilus influenzae and Branhamella catarhallis.

The in vitro activity of ceftibuten, a new orally administered cephalosporin, was assessed against clinical isolates of Haemophilus influenzae and Branhamella catarrhalis. The activity of ceftibuten was compared to that of ampicillin, amoxicillin-clavulanic acid, and three oral cephalosporins, cefaclor, cefuroxime, and cefixime. With the exception of rare beta-lactamase-negative ampicillin-resistant strains of H. influenzae, resistance to ceftibuten was not observed with any of the study isolates. Ceftibuten was more active than amoxicillin/clavulanic acid for beta-lactamase-positive and -negative strains of H. influenzae; it was less active than this combination for B. catarrhalis. Ceftibuten was essentially equivalent in activity to cefixime against both Haemophilus and Branhamella but more active than cefaclor and cefuroxime against these two organisms.

Amoxicillin↗

High-performance liquid chromatographic determination of cephalosporin antibiotics using 0.3 mm I.D. columns.

Four cephalosporins, cefazolin, ceftizoxime, cefaloridine and cefaclor, were determined using a novel microbore high-performance liquid chromatographic system designed to be entirely compatible with direct liquid interfacing (DLI) for mass spectrometric analysis. The chromatographic support was a 5-micron C18 column of 0.3 mm I.D., compared with the usual microbore column diameters of 1-2 mm. The mobile phase contained no buffers or salts which may have caused column blocking or mobile phase crystallization, and the use of a concentration column allowed the injection of large volumes of analyte (up to 500 microliters). The assay was reproducible, the relative standard deviations being less than 20% within-day and between-day for all the drugs. The detection limit for cefaloridine and cefazolin was 1 ng and for cefaclor and ceftizoxime 5 ng.

Cefaclor↗