Antibacterial activity of cefaclor (CCL), a new oral cephalosporin antibiotic, was examined and compared with cephalexin (CEX) both in vitro and in vivo.
CCL showed a broad antibacterial spectrum similar to CEX in vitro. Particularly it showed higher antibacterial activity to E. coil and P. mirabilis than CEX did.
Behavior of CCL to inactivating enzymes produced by microorganisms was similar to that of CEX. CCL was somewhat unstable to penicillinase-type enzymes than CEX was. Similar to CEX, CCL was inactivated by cephalosporinase-typenzymes.
In in vivo mouse-protection experiments. CCL showed lower ED₅₀ in mice infected with susceptible organisms than CEX did and thus showed better therapeutic effect.

View full abstract

The antibacterial activities of cefaclor were compared with those of cephalexin and cefatrizine in 1471 strains of aerobic gram-positive cocci, aerobic gram-negative bacilli and anaerobic bacteria which were isolated from clinical specimens in Clinical Laboratories, Juntendo University Hospital from 1976 to 1978.
Bactericidal action of cefaclor was compared with that of cephalexin in the liquid medium by use of one strain of E. coli isolated from a patient with meningitis.
1. Antibacterial activity of cefaclor was higher than that of cephalexin, and similar to or slightly lower than that of cefatrizine, although it varied with the kinds of bacteria.
2. Cefaclor demonstrated the highest antibacterial activity against Groups A. B and G Hemolytic Streptococci and Pneumococci, followed by the activity against Salmonella, Staphylococcus epidermidis, Staphylococcus aureus, Haemophilus influenzae, Citrobacter diversus, Klebsiella, Proteus mirabilis, Peptococcus, Peptostreptococcus, Veillonella and Propionibacterium. Cefaclor showed high antibacterial activity also against E. coli and Vibrio parahemolyticus. However, resistant strains were observed in Haemophilus influenzae, Citrobacter diversus, Klebsiella, Proteus vulgaric, Peptncoccus Propionibacterium and E. coli. Antibacterial activity of cefaclor was low against Serratia, Baderoides, Fusobacterium and Enterococci.
3. Cross resistance was observed among cefaclor, cefatrizine and cephalexin.
4. Antibactericidal action of cefaclor was similar to that of cephalexin and was thought not to be much potent.

View full abstract

The in vitro and in vivo activity of cefaclor was investigated. The activity of cefaclor was compared with that of cephalexin.
Cefaclor and cephalexin were active against anaerobic bacteria except Bacteroides species. With regard Bacteroides species, cefaclor was less active than cephalexin,
Chemotherapeutic effects of cefaclor on experimental subcutaneous abscess of mice with Fusobacterium necrophorum was demonstrated.

View full abstract

The in vitro and in vivo antibacterial activity of cefaclor (CCL), a new oral cephalosporin antibiotic, was compared with that of cephalexin (CEX). The following results were obtained.
1) CCL showed broad antibacterial spectrum against gram-positive and gram-negative bacteria. The antibacterial activity of CCL was 2 to 8 times superior to that of CEX.
2) Sensitivity distribution of clinical isolates to CCL exhibited 2 to 8 times stronger activity than CEX against S. aureus, E. coli, K. pneumoniae and P. mirabilis.
3) Influence of medium pH and inoculum size on in vitro antibacterial activity of CCL showed the same tendency to CEX. The antibacterial activity of CCL was slightly influenced by the addition of horse serum.
4) The effect of CCL on growth curve of S. aureus, E. coli and K. pneumoniae was also studied. CCL had a stronger bactericidal and lytic activity against E. coli and K. pneumoniae than CEX does.
5) In protective effect studies on experimental mice infected with S. aureus, S. pyogenes, S. pneumoniae, E. coli and K. pneumoniae respectively the activity (ED₅₀) of CCL was 4 to 10 times superior to that of CEX. In E. coli and K. pneumoniae infections with large challenge dose CCL was much more effective than CEX was.

View full abstract

As an aid for seeking an optimal method for dosing cefaclor (CCL), a new oral cephalosporin antibiotic, against E. coli KC-14 and K. pneumoniae KC-1 infections in mice, both in vitro and in vivo antibacterial activities of CCL were studied using cephalexin (CEX) as control drug, and the following results were obtained.
1. Bactericidal action of CCL on E. coli KC-14 and K. pneumoniae KC-1 was superior to that of CEX in vitro.
2. E. coli KC-14 and K. pneumoniae KC-1 damaged by 1 MIC of both drugs, when free from the drugs immediately began to regrow; however, unlike CEX, higher concentration (5 or 10 MIC) of CCL caused a lag time until regrowth of these bacteria in vitro.
3. The therapeutic effect of CCL on E. coli KC-14 and K. pneumoniae KC-1 infections in mice was superior to that of CEX. On the other hand, the thereutic effect in multiple administrations of both drugs on these infections was as effective as their single administrations.
4 The factor of influencing the therapeutic effect of both drugs was found to be total duration of both of the effective concentration.

View full abstract

Cefaclor (CCL) is a new oral semi-synthetic cephalosporin which possesses a unique chemical structure substituted with chlor atom for the 3-methyl group present in cephalexin (CEX) molecule. It substantially resembled to CEX in antibacterial spectra, but the superiority of CCL to CEX was consistently observed in antibacterial activity.
Susceptibility of 675 clinical isolates of pathogenic bacteria to cefaclor was measured by an agar dilution method and compared with those of CEX, cefatrizine (CFT) and amoxicillin (AMPC). A majority of the tested strains of gram-positive cocci other than enterococci, Enterobacteriaceae (E. coil, Klebsiella sp., P. mirabilis) and H. influenzae were inhibited at below 3.13μg/ml of CCL. CCL were twice to eight times more active than CEX. Most of the AMPC-resistant strains of these bacteria were susceptible to CCL and no cross resistance was observed between two antibiotics. Most isolates of indole-positive Proteus, Citrobacter, Enterobacter tended to be resistant.
The activity of CCL was greater in acidic medium than in alkaline medium because of unstable nature in alkaline solution, and were curtailed in the presence of human serum. CCL showed more pronounced inoculum effect than CEX, especially in the β-lactamase producing strains. CCL was stable to some of β-lactamases but tends to be more hydrolysable by penicillinase type than CEX.
One of the most characteristic features of CCL was a rapid bactericidal action against gram-negative bacteria. The time-course experiment of MBC against E. coil-clinical isolates clearly revealed that the short-time MBCs were always lower than the MICs. Changes of viability and morphological observations of the treated cells also supported rapid bacteriolytic action of this antibiotic.
Regrowth phenomenon of the CCL-treated bacteria was explained by the decrease of the concentration in the medium below the short-time MBC, and the regrown cells did not acquire resistance to CCL.

View full abstract

The protective effects of cefaclor, a new oral cephalosporin antibiotic, against experimental intraperitoneal and urinary tract infections in mice were compared with those of cephalexin.
Cefaclor showed considerably higher protective effect than cephalexin in mice systemically infected with various gram-positive and gram-negative bacteria, including Streptococcus pyogenes, Klebsiella pneumoniae, Escherichia coli, Haemophilus influenzae, Proteus mirabilis and Enterobacter aerogenes. However, there was no significant difference between two antibiotics in the influence of inoculum size of bacteria and dosing schedule.
Against experimental urinary tract infections with E. coli and P. mirabilis, cefaclor was also more effective than cephalexin.

View full abstract

Cefaclor (CCL), a new oral cephalosporin antibiotic, was administered to mice, rats and dogs in either single or multiple doses ranging from 12.5 to 100mg/kg, for comparison of its pharmacodynamics with that of cephalexin (CEX).
After oral doses, both antibiotics produced similar peak concentrations in plasma, which were proportional to dosings, but CCL disappeared more rapidly in plasma than CEX. The comparative studies between oral and parenteral administration revealed that CCL was quite efficiently absorbed from the gastrointestinal tract and its bioavailability was estimated from the area under curves to be 89, 86 and 77% in mice, rats and dogs, respectively.
In rats, 9.2% of the doses was excreted into bile fluid but eliminated through kidney via enterohepatic recirculation. Biliary elimination in dogs was only marginal. Thus, CCL, like CEX, was primarily eliminated by renal excretion. The urinary recovery of CCL in mice, rats and dogs after oral doses was 47, 43 and 34% of the doses, respectively. The unstable properties might be involved in the low recoveries of CCL in comparison to those of CEX ranged 66 to 76%.
Antibiotic activity found in plasma and urine was identified to unaltered CCL. In some cases, a single active metabolite was detected in urine after oral administration but its amount was only minute as representing less than 0.1% of the total antibiotic activity recovered into urine.
There was no accumulation of antibiotic in plasma and urine during multiple dosings of CCL in dogs.

View full abstract

The purpose of these studies was to evaluate the absorption, distribution and excretion of cefaclor in rats. ¹⁴C-labeled cefaclor (¹⁴C-CCL) at 25 and 50mg/kg was administered orally and also 25mg/kg of the same compound was given intravenously to rats.
1) The peak level in blood was obtained within 1 hour after oral administration of 25 or 50mg/kg of ¹⁴C-CCL to rats. The maximum blood level of CCL after oral administration of 50 mg/kg of ¹⁴C-CCL was twice as high as that in rats given 25mg/kg. Both radiocarbon blood level curves obtained following oral administration of 25 and 50mg/kg of ¹⁴C-CCL had similar pattern of decrease. Radioactivity one-tenth of the maximum level was observed within 8 hours after oral administration of either 25 or 50mg/kg of ¹⁴C-CCL. The radioactivity of the blood at 2 hours after intravenous administration was 10% of the blood level of radiocarbon at 5 min.
2) The urinary and fecal excretion of total radioactivity in rats following oral and intravenous administration of ¹⁴C-CCL was complete within about 48 hours. Larger amounts of radiocarbon were excreted in the urine than in the feces, even after oral administration. The amounts of radiocarbon in urine recovered from both groups were about the same. Therefore, the results suggested that CCL was efficiently absorbed from the gastrointestinal tract.
3) About 20% of the administered radiocarbon appeared in the bile fluid within the initial 12 hours, only a portion of it was eliminated via the bile fluid while in the second 12-hour period.
4) In experiments on the distribution of ¹⁴C-CCL, maximum radioactivities were detected in almost all tissues within one hour after administration of ¹⁴C-CCL to male rats. High radioactivities were found in the digestive tract, kidney, liver and aorta, but considerably lower radioactivity in the brain. The thyroid gland, adrenal gland and colon each had 20-40% of the maximum level, and the other organs had several percent of the maximum activity at 24 hours after administration.
5) The maximum level of radioactivity in maternal tissues was determined 0.5-1.0 hour after administration of ¹⁴C-CCL to pregnant rats. The highest activities were observed in kidney and liver and lower activities in plasma, uterus, blood, lung, ovarium and placenta in that order. After 24 hours, less than 5% the maximum level in each tissue was found in all tissues except the amniotic fluid. In the fetus, the radioactivity peaked 4 hours after administration to the maternal body. In this period radiocarbon concentrations were the same for the liver and kidney of the fetus and the maternal plasma.
6) In general, the distribution of radiocarbon examined by autoradiograph on the whole body of a male rat was very similar to that found by quantitative determination in each tissue. After 24 hours, some amounts of radioactivities were found only in the intestinal contents. In pregnant rats. radiocarbon was distributed in the placenta but was not significantly observed in the fetuses.

View full abstract

¹⁴C-labeled cefaclor (¹⁴C-CCL) at 50 mg/kg was orally administered to evaluate absorption and excretion of CCL in dogs and monkeys.
1) The blood level peak of radioactivity was observed at 30 min. in dogs and at one hour in monkeys after oral administration of ¹⁴C-CCL.
2) The plasma level peak of microbiological activity corresponding to unchanged CCL was obtained at 30 min. in monkeys after oral administration of CCL. The microbiological activities declined until 4 hours in the manner of t1/2: 0.8 hours. No significant microbiological activities of CCL were recognized in plasma at 8 hours after administration. In dogs, the maximum microbiological activities of CCL in plasma were detected at one hour and declined in the manner of t1/2: 1.6 hours until 12 hours.
3) Urinary and fecal excretion of the total radioactivity of the administered ¹⁴C-CCL was completed during 48 hours after administration. The amounts of urinary excretion of radiocarbon were much larger than those of fecal excretion. Fifty-five percent of the administered radiocarbon of ¹⁴C-CCL was excreted in the urine, while 25% was recovered in the feces during 48 hours after administration to monkeys.
In dogs, 54% of the administered ¹⁴C-CCL was detected in the urine and 39% was excreted in feces during 48 hours after administration.
4) The urinary recovery of the unchanged form (microbiologically active substance) of CCL was 16-21% of the administered CCL in monkeys. In dogs, the urinary recovery of unaltered microbiological activity of CCL was totalled to 7-17% of the administered amounts during 24 hours after administration.

View full abstract

¹⁴C-labeled cefaclor (¹⁴C-CCL) at 50 mg/kg was orally administered to study its absorption, excretion and biotransformation in mice, rats, rabbits, dog and monkeys.
1) Recovery of urinary and fecal radiocarbon of the administered ¹⁴C-CCL (50 mg/kg) was 63% in rats (for 24 hours), 73% in mice (for 24 hours) and 65% in rabbits (for 48 hours). The recovery of fecal radiocarbon was 28% in rats (for 24 hours), 17% in mice (for 24 hours) and 4% in rabbits (for 48 hours).
2) The percent recovery of the unchanged CCL was about 40% of the administered CCL in the urine of mice, rats and rabbits during 8 hours after administration. Several biotransformed compounds which had been derived from ¹⁴C-CCL were found by TLC in the urine of these animals. The amount of each metabolite in urine were less than 5% of the administered ¹⁴C-CCL. In dogs and monkeys, the amounts of urinary excretion of unchanged CCL were less than those in mice, rats and rabbits.
3) The percent recovery of radiocarbon of the administered ¹⁴C-CCL (50 mg/kg) in rats was 33% in bile, 52% in urine and 7% in feces. In the bile fluid, the ratio of the amount of unchanged ¹⁴C-CCL divied by that of the changed compounds was about one-seconds.

View full abstract

Bactericidal effect of cefaclor was compared with that of cephalexin using an in vitro pharmacokinetic model system simulating the serum levels of cefaclor and cephalexin obtained after a 250 mg oral dose in healthy adult volunteers.
Three standard strains, Staphylococcus aureus FDA 209P (S. aureus ATCC 6538P), Escherichia coli NIHJ JC-2 and Klebsiella pneumoniae ATCC 10031 were used. The strains were inoculated initially (10⁵ cells/ml) in Antibiotic Medium No.3 (ABM 3) and were exposed to various concentrations of cefaclor every 8 hours or to cephalexin every 6 hours, during a 24-hour period. These exposure times are equivalent to the clinical dosage regimens of cefaclor three times daily and cephalexin four times daily. The colony count of viable cells was determined every hour for 24 hours. It was assumed that this procedure would simulate the exposure of the bacteria to the antibiotics in actual clinical therapy.
The MIC values determined by broth dilution method in ABM 3 at the inoculum size of 10⁵ cells/ml against S. aureus, E. coli and K. pneumoniae used in this experiment were 6.25, 12.5 and 6.25μg/ml for cefaclor, and 3.13, 12.5 and 6.25μg/ml for cephalexin, respectively.
In the case of S. aureus, with the exposure to cefaclor every 8 hours or to cephalexin every 6 hours, the number of surviving cells decreased, but tended to increase in the absence of cefaclor and during the trough of cephalexin concentration. There was no marked difference in the number of surviving S. aureus at the end point of this experiment. The results suggest that the inhibitory effect of cefaclor by 250 mg three times daily would be similar to that of cephalexin by 250 mg four times daily in a clinical situation.
In the case of E. coli, the number of surviving organisms exposed to cephalexin decreased initially, but rapidly increased again during the trough of cephalexin concentration and by 18 hours the number increased to a very high level in spite of additional exposure to cephalexin every 6 hours. In contrast, after the first exposure to cefaclor, the number of surviving E. coli decreased rapidly, then it increased during the absence of cefaclor. However, after the second exposure at 8 hour interval, the number of surviving E. coli was reduced to zero.
The third experiment on K. pneumoniae demonstrated a similar result to that obtained with E. coli. The number of surviving K. pneumoniae exposed to cephalexin decreased initially, then it increased during the trough of cephalexin concentration. However, after the following exposures, it began to decrease again, then it rapidly increased during the troughs. The number of surviving K. pneumoniae at every 6 hour after each exposure increased step by step to a level above that of last exposure. On the other hand, after the first exposure to cefaclor, the number of surviving K pneumoniae decreased rapidly, then it increased during the absence of cefaclor, but after the second exposure, it was reduced to zero.
It should be noted that although these strains of E. coli and K. pneumoniae showed identical MIC values for cefaclor and cephalexin and the interval between the exposures to cefaclor was longer than that to cephalexin, the bactericidal effect of cefaclor against these strains was much stronger than that of cephalexin.
These results demonstrate that the bactericidal effect of cefaclor is greater than that suggested by conventional MIC values, and support the adequacy of a three times daily dosage regimen for cefaclor.

View full abstract

Cefaclor (CCL), a new cephalosporin antibiotic, was administered orally to twenty one healthy adult male volunteers to study the degree of safety and pharmacological properties. In single dose studies, 14 volunteers were randomly assigned to the doses of 250 mg and 500 mg of CCL or 250 mg of cephalexin (CEX) with or without food, then they received different dose every weekend for 4 weeks. In multiple dose studies, 7 volunteers received 500 mg of CCL in capsules every 6 hours for a week.
Tolerance of administered CCL was, in general, good and no side effect or adverse reaction was found except 3 cases with transient mild gastrointestinal disturbance in multiple dose studies.
CCL plasma concentrations usually peaked at 45 minutes after the dosing without food and steadily declined with no CCL detectable in plasma at 6 hours. The mean peak plasma levels of CCL were 7.42μg/ml for a 250 mg and 13.04μg/ml for a 500 mg and the plasma halflife calculated was about 30 minutes. During the 0- to 8- hour interval, about 70% of the total dose was excreted in urine.
From the comparative pharmacokinetic studies of CCL and CEX, the peak plasma concentration and the plasma halflife of CCL were a bit lower and shorter than those of CEX without food.
In the case of dosing 30 minutes after breakfast, CCL plasma concentrations peaked at 2 hours after the administration and the mean peak plasma levels were 3.22μg/ml for a 250 mg and 5.33μg/ml for a 500mg. Plasma levels of CCL were clearly influenced by dosing with food, however, equivalent value of AUC (area under the curve) suggests the quite similar bioavailability of CCL by dosing without food. Urinary excretion of CCL was also delayed at first by dosing with food, but about 70% of the total dose was excreted in urine during 8 hours.
In the case of multiple dose studies, the similar patterns of plasma concentrations and urinary excretion derived from the 500 mg single dose study were seen everytime examined and no plasma accumulation of CCL was demonstrated.

View full abstract

Cefaclor, a new oral cephalosporin, has been investigated to give following results. A pharmacokinetic study of cefaclor was conducted in 6 healthy male volunteers in the fasting state (a) and with food which was divided light meal group (b) and heavy meal group (c). After twice oral doses of 250 mg of cefaclor, the mean peak concentration in plasma were 9.0 and 9.3μg/ml each at 1/2 hour in (a), 4.2 at 11/2 hour and 4.2 at 3 hour in (b), 2.4 at 2 hour and 2.4 at 3 hour in (c), respectively. There was no significant differences in the area under curves (AUC) during three groups. The urinary excretion rates were 82.9, 81.0 and 78.1% of the oral twice doses in during 10 hours, respectively.
Fifty two patients with respiratory tract infections and urinary tract infections were treated with cefaclor of 750 mg t. i. d. dose. Eleven patients of all were cured excellent, 27 were good, 5 were fair and 9 were failed. All of 6 patients with Staphylococcus aureus, 4 of 5 Pneumococcus, 4 of 5 Haemophilus influenzae and 14 of 19 Escherichia coli was eliminated. Two patients were occured mild nausea and gastric disturbance. No laboratory abnormalities were observed.

View full abstract

Thirteen cases of respiratory tract infections including 8 chronic bronchitis, 3 bronchiectasis, 1 bronchopneumonia and 1 acute bronchitis, caused by H. influenzae, H. parainfluenzae, E. coli Enterobacter, S. pneumoniae and S. hemoliticus were treated respectively with cefaclor 250 mg t. i. d. for seven to fourteen days. Eleven cases showed good response in bacteriological and clinical findings.
Seven cases of urinary tract infections including 6 acute pyelitis and 1 acute cystitis caused by E. coli were treated with cefaclor 250 mg t. i. d. or q. i. d. for three to fourteen days and good response was obtained in all cases.
No side effect or adverse reaction was observed except one case of mild diarrhea.

View full abstract

Cefaclor was orally administered to 11 patients with urinary tract infection and 5 patients with respiratory tract infection. The patients received the drug for 3 to 21 days in doses of 0.5 to 1g/day. All patients with urinary tract infection and 3 of 5 patients with respiratory tract infection responded well to therapy. For the side effect of cefaclor, there was rash in only one patient.

View full abstract

Cefaclor was administered orally to 15 patients with respiratory tract infection and to 5 patients with urinary tract infection.
The clinical effectiveness was good in 11, fair in 3, and poor in 4 cases. In the remaining 2 cases, however, the clinical results were unable to be judged.
No adverse clinical reactions occured. Either a minimal decrease of leucocytes within the normal range in 2 and a mild eosinophylia in 1 was the only laboratory data changed.

View full abstract

Laboratory and clinical studies on cefaclor were performed and the following results were obtained
1) The in vitro antibacterial activity of cefaclor and cephalexin was compared against 36 clinical isolates of E. coli (19), P. mirabilis (5), Citrobacter (3), S. epidermidis (3), Klebsiella (2), Enterobacter (2) and H. parainfluenzae (2).
Cefaclor was 2 to 8 fold more active than cephalexin against these clinical isolates.
2) Cefaclor was clinically applied to 28 cases of bacterial infection, including 10 cases of respiratory infection, 11 cases of urinary tract infection, one case of acute cholecystitis and 6 cases of acute enteritis.
The results obtained were good in 24 cases and poor in 4 cases. The effective rate was 85.7%.
3) Transient nausea was seen in one case as a side effect. No abnomal laboratory findings were seen except in one case with transient slight increase in GOT and GPT values.

View full abstract

1. Antibacterial activity.
MIC of cefaclor (COL) to E. coli was distributed between 0.39 and >100μg/ml with its peak at 0.78μg/ml. Twenty-five out of 27 strains (92.6%) were inhibited their growth with 3.13μg/ml or less of CCL.
MIC of CCL to 50 strains of K. pneumoniae ranged between 0.39 and 100μg/ml with its peak at 0.78μg/ml.
Thirty-three out of 50 strains (66%) were inhibited their growth with 6.25μg/ml or less of CCL. Thus, CCL showed stronger antibacterial activity than cephalexin, cephalothin and cephaloridine.
2. Blood levels and urinary excretion
When a 250 or 500 mg dose of CCL was administered orally to healthy adult volunteers in fasting condition, the peak serum level was attained 45 minutes after administration. The peak level was 8.19 and 11.5μg/ml, respectively. Recovery of CCL in urine up to 6 hours was 69.7% and 70.6%, respectively.
3. Clinical results.
Cefaclor was administered to 17 patients (14 with urinary tract infection and 3 with respiratory tract infection). Clinical response was satisfactory in 13 cases (81%) and unsatisfactory in 3 cases.
In one case, skin rash developed. No other serious adverse reactions were observed.

View full abstract

Some laboratory and clinical studies on a new cephalosporin antibiotic for oral use, cefaclor, were performed and the following results were obtained.
1. The MIC values of cefaclor to clinical isolates of E. coli, Klebsiella and P. mirabilis were superior to cephalexin in general, being almost equal to those of cefatrizine. There found cross resistance among these three derivatives of cephalosporin.
2. The heavier food intake and shorter interval of 30 minutes between drug administration led later and lower blood peak values, but urinary recovery rate did not change so much among them.
Cross over test of cefaclor and cefatrizine revealed that cefaclor showed higher peak blood level and subsequent faster reduction.
3. The measurement of blood and urine samples using high performance liquid chromatography showed the good correlation of the values of cefaclor between those obtained from bioassay.
4. Clinically, cefaclor was administered to four cases of upper respiratory tract infections and four cases of urinary tract infections. The result was evaluated as good in six, fair in one and indeterminable in one case. Neither side effect nor abnormalization of laboratory findings was observed.

View full abstract

MICs of CCL and CEX were examined by agar dilution method. Fifty four strains of S. aureus, 29 strains of E. coli and 23 strains of K. pneumoniae isolated from clinical specimens were used for determinetion.
The MICs of CCL for 36 strains of S. aureus which were sensitive to CEX (1.56-3.13μg/ml of MICs) ranged from 0.78 to 3.13μg/ml with an inoculum of a loopful of 100 fold dilution of overnight cultured broth. Eleven strains were resistant to CCL and CEX with MICs of 25μg/ml or above.
The MICs of CCL for 29 strains of E. coli ranged from 12.5μg/ml to above 400μg/ml with an inoculum of a loopful of overnight cultured broth. MIC was affected by inoculum size. With an inoculun of a 100 fold dilution broth, MICs of these strains ranged from 0.78 to 50μg/ml.
The MICs of CCL for 23 strains of K. pneumoniae ranged from 1.56μg/ml to 50μg/mlwith an inoculum of overnight culture in a heart infusion broth. However, the MICs of CCL for these strains for which the MIC of CEX ranged from 3.13 μg/ml to 6.25μg/ml were altered among 0.78μg/ml to 3.13μg/ml when an inoculum was a 100 fold dilution. CCL was more active than CEX for S. aureus, E. coli and K. pneumoniae.
Four out of 5 patients with tonsillitis and 4 out of 6 patients with acute pyelonephritis were successfully treated with daily dosis of 750 mg of CCL, respectively. All 6 patients with acute cystitis were also successfully treated with 750mg of CCL a day. One patient complained anorexia during the administration of CCL.

View full abstract

1) The MICs of cefaclor, using plate dilution method, against E. coli and Klebsiella were found to be more active than those of cephalexin.
2) Concentrations of cefaclor were determined in serum and urine of 3 normal cases. The concentrations of serum were 5.4 μg/ml at 0.5 hour, 4.1μg/ml at 1 hour, 1.1μg/ml at 2 hour and less than 0.1μg/ml at 4 hour after 250mg oral administration. Average urinary recoveries in these volunteer after 250mg oral administration were about 70% during 6 hours.
3) Cefaclor was administered to a total of 7 cases, 5 cases of urinary tract infection and 2 cases of respiratory tract infection at a dosis of 750mg per day. Clinical response of cefaclor obtained in those cases was good in 6 cases.
No side effects were experienced.

View full abstract

Fundamental and Clinical studies on cefaclor, a new oral cephalosporin antibiotic, were performed, and following results were obtained.
1) Antibacterial activity
Cefaclor was more active than CEX against E. coli, Klebsiella pneumoniae, Proteus mirabilis and Haemophilus influenzae.
2) Absorption and excretion
Concentrations of cefaclor in serum and urine after single oral administration of 250mg were measured of 6 male healthy adult volunteers in a cross over method at a time of fasting and non fasting.
The mean peak concentrations in serum were 5μg/ml at 30 minutes in fasting cases, and 2.2μg/ml at 2 hours in non fasting cases. The influence of meal was appearent from blood levels of cefaclor.
And the mean urinary recovery during the first 6 hours of administration was 78.7% in fasting cases and 68.0% in non fasting cases.
3) Clinical results
Cefaclor was administered in 19 patients of various infections. The therapeutic effect of the drug was estimated as good in 14 cases, fair in 2 cases and poor in 3 cases. The efficacy rate was 73.7%. Particularly in the group of 6 cases with secondary infection of pulmonary emphysema and bronchiectasis, the effect was good in 1 case, fair in 2 cases and poor in 3 cases.
No side effect was seen.

View full abstract

Plasma levels of cefaclor in four elderly patients (mean age: 74.3) were determined after oral administration of 250 mg of the drug. Peak concentration in plasma ranged from 8.0 to 20 μg/ml (mean 14.5). Interval between administration of the drug and peak concentration was 30 min. in two, and 90 min. 240 min. respectively. These results suggest that absorption of the drug from intestine was not uniform in elderly patients, presumably depending on peristalsis, pH in GI contents and other physiochemical characteristics of GI of the aged. In all patients, antimicrobial activity was detected in plasma at 6 hours following administration.
Clinical evaluation was performed on 3 cases with respiratory infection and 5 cases with UTI of the aged. Excellent response was observed in three, good in three, fair in one and poor in one. No adverse effect was observed.

View full abstract

Clinical investigations were performed on cefaclor and the results obtained were as follows;
Cefaclor was found to be effective in 9 out of 10 cases of acute bronchitis, 2 cases of chronic bronchitis, 16 out of 19 cases of acute pyelonephritis, while it was ineffective for each 1 case of chronic cystitis, cholecystitis and skin abscess.
When these results were inspected by causative organisms isolated, cefaclor was active against 8 of 11 strains of E. coli, 2 of strains of K. pneumoniae, 3 strains of Micrococcus, 2 strains of H. influenzae and each 1 strain of P. mirabilis and D. pneumoniae.
Laboratory findings revealed abnormalities of liver functions in 2 cases.

View full abstract

Fundamental and clinical studies on cefaclor (CCL), a new oral cephalosporin antibiotic, were carried out and the results obtained were as follows:
1. In vitro antibacterial activity
Peaks of MIC distribution of CCL against various clinical isolates such as S. aureus, E. coli, Klebsiella, P. mirabilis and P. vulgaris were 3.12μg/ml, 25μg/ml, 1.56μg/ml, 1.56μg/ml and≥100μg/ml at a higher inoculum size, and 1.56μg/ml, 3.12-6.25μg/ml, 0.78μg/ml, 1.56μg/ml and≥100μg/ml at a lower inoculum size, respectively.
CCL was 2-8 times as potent as CEX against these tested organisms except P.vulgaris.
2. Serum levels and urinary recovery
Four healthy adult volunteers were orally administered CCL at a dose of 500mg.
The peak serum concentrations were 4.6-13.6μg/ml at 30-60 minutes after administration, and afterward rapidly decreased, serum concentrations weren't detected in 3 of 4 subjects at 4 hours after administration.
Urinary recoveries for 6 hours were 68.8-95.4%.
3. Clinical results
CCL was orally administered to 7 cases with respiratory tract infections and 7 cases with urinary tract infections, totally 14 cases, at a daily dose of 1.5-3.0g for 6-14 days, and the clinical effects obtained were excellent in 2 cases, good in 8 cases, fair in 1 case and poor in 3 cases.
Adverse effects observed were fever and rash in 1 case. It is considered by its improved pattern that CCL has a decreasing effect of fever.

View full abstract

Cefaclor, a cephalosporin derivative with a characteristic chemical structure, was examined as to its in vitro activity against clinically isolated bacteria, as well as to its effectiveness in clinical cases. The results obtained were as follows:
1) Antibacterial activity: Cefaclor (CCL) was found to be more active than cephalexin (CEX): MICs of CCL and those of CEX against Staphylococcus aureus strains were in the proportion of 1:2. The MICs of CCL against E.coli or Klebsiella strains varied markedly according to the inoculum size: Although the proportion of MICs of CCL to those of CEX was 1:2 by 10⁸ cell/ml inoculum, reduction of the concentration to 10⁶ /ml yielded remarkable lowering of the proportion down to 1:16. Strains of Proteus mirabilis, too, were sensitive to the drug, the MICs being in proportion of 1:16 against CEX even in the inoculum concentration of 10⁸ /ml. Strains of other Proteus groups as well as those of Pseudomonas were mostly resistant to CCL similarly to CEX.
2) Clinical trials: Twenty-four patients (19 with respiratory tract infections, 4 with urinary tract infections and 1 with colitis) were treated with peroral dosage of CCL 750-1500 mg/day. Fifteen out of 16 cases of RTI (three were excluded because of difficulties in evaluation) well responded to the treatment, and the remaining one, too, responded fairly. Especially, two cases of lung abscess, complicating SUE or bronchial asthma, could be cured by the treatment, actually demonstrating the effectiveness of CCL. All of the four cases of UTI, as well as one case of colitis probably caused by Salmonella, were successfully treated with CCL.
Neither side effects nor abnormal laboratory findings were caused by the administration, except for one case of inappetence.
These results obtained should suggest the sufficient clinical availability of the drug.

View full abstract

Laboratory and clinical investigations were performed on cefaclor (CCL), and the results obtained were as follows;
1) Sensitivity of clinically isolated strains to CCL was tested by the agar plate dilution method, and compared with that of cephalexin. Growth was inhibited at 90.0% of 50 strains of Staphylococcus aureus, 62.0% of 50 strains of Klebsiella pneumoniae respectively at MIC of 6.25μg/ml or less, while all the strains of Proteus vulgaris, Serratia marcescens and Pseudomonas aeruginosa were resistant to CCL. The activity of CCL was equivalent to cephalexin against E. coli.
2) Serum concentration of CCL (mean) 1 hour after ingestion of first morning doses of 250mg was observed 0.8μg/ml and 2.5μg/ml at 2 hours, 2.2μg/ml at 4 hours. Similarly, it was observed 2.2μg/ml, 3.4μg/ml and 1.8μg/ml after oral administration of 500mg doses. Cumulative urinary excretion of CCL was 60 per cent during the first 6 hours.
3) Effective clinical result was obtained with CCL in 8 of 10 patients treated. No side effect was observed in all patients.

View full abstract

Cefaclor was orally administered to 16 patients with bacterial infection, including 9 cases of respiratory tract infection and 7 cases of urinary tract infection. As the results, overall clinical response was excellent in 2 cases, good in 7 cases and fair in 3 cases.
No marked side effects were observed except for one case with eruption.

View full abstract

Cefaclor, an oral cephalosporin developed recently, was studied for the antibacterial activity and clinical efficacy.
1. Antibacterial activity.
Cefaclor demonstrated an excellent antibacterial activity against gram-positive cocci such as S. aureus, S. pyogenes, etc., E. coli and K.pneumoniae. No antibacterial activity was shown to S. faecalis, Serratia and P. aeruginosa. Antibacterial activity of cefaclor was much affected by inoculum size. When compared with cephalexin (CEX) in the inoculum size of 10⁶ cells/ml, antibacterial activity of cefaclor was twice that of CEX against gram-positive cocci and 4 to 8 times that of CEX against gram-negative bacilli.
Cefaclor showed less activity than CEX in sensitivity test by disc method.
2. Clinical efficacy.
Cefaclor was administered to 14 patients with pneumonia (2 patients), chronic bronchitis (1), tonsillitis (5), cervical lymphadenitis (1), hordeolum (1), acute cystitis (1) and chronic pyelonephritis (3). The daily dose ranged from 0.75 to 1.5 grams, and duration of administration from 2 to 24 days. The result was good in 9 cases, fair in 2, failure in 2 and unknown in one. Thus, considerably good clinical result was obtained with the drug. As to the efficacy by causative bacteria, cefaclor showed good efficacy to the infections by S. aureus and E. coli.
No adverse effect was observed except diarrhea in one patient. No abnormality was seen at all in clinical laboratory studies.

View full abstract

Cefaclor is a new oral semisynthetic derivative of cephalosporin. The clinical effects of cefaclor were investigated, and the following results were obtained.
Cefaclor was administered to 36 patients orally in the daily dose of 0.75-1.5g for 6 to 21 days.
1) Acute respiratory tract infections were observed excellent in 3 cases, good in 10 cases and poor in 4 cases out of 17 cases.
2) Chronic respiratory tract infections were observed good in 3 cases, fair in 5 cases and poor in 5 cases out of 13 cases.
3) Urinary tract infections were observed excellent in 2 cases, good in 1 case and fair in 2 cases out of 5 cases.
4) As to side effects of drug, a transient dizziness, an allergisches eruption and an elevation of GOT and GPT were noted in each 1 case, respectively.

View full abstract

Laboratory and clinica, studies on cefaclor (CCL), a new antimicrobial agent, were carried out and the results were as follows.
1) Antibacterial activity:
Minimum inhibitory concentrations (MICs) of CCL against total 678 strains consisting of 661 strains isolated from various clinical specimens (Staphylococcus aureus 52, β-Streptococcus 27, Salmonella 36, Citrobacter freundii 66, Citrobacter diversus 37, Citrobacter intermedius 8, Escherichia coli 54, Shigella 46, Klebsiella aerogenes 27, Enterobacter aerogenes 27, Enterobacter cloacae 27, Serratia marcescens 27, Proteus vulgaris 44, Proteus mirabilis 27, Proteus rettgeri 27, Proteus morganii 27, Haemophilus influenzae 31, Haemophilus haemolyticus 6, Haemophilus parainfluenzae 45, Haemophilus parahaemolyticus 20) and 17 standard strains subcultured in our department, were compared with those of cephalexin (CEX). The antibacterial activity of CCL was stronger than that of CEX in general.
2) Absorption and excretion in man:
Two healthy male adults were given 500mg of CCL orally at fasting time and the peak serum levels were 8.3 and 12.8μg/ml one hour after administration. Urinary recovery rates were 75% 1 to 2 hours and 90% 4 to 6 hours after administration.
3) Serum and sputum levels in chronic respiratory infections
Two patients with bronchiectasis were given 500mg of CCL orally at fasting time. The peak serum levels were 1.0 and 2.3μg/ml 2 hours after administration, and the peak sputum levels were 0.13 μg/ml 0 to 1 hour and 0.17μg/ml 4 to 5 hours after administration.
4) Clinical effect and adverse reaction:
Twenty one cases with pulmonary infections (bronchopneumonia 13, acute bronchitis 1, chronic bronchitis 3, lung abscess 1, bronchiectasis 3) and 6 cases with urinary tract infections (cystitis 2, pyelonephritis 4) were given 750-1, 500 mg of CCL daily for 5-20 days. Overall efficacy rate was 77%(20/26)(excellent 11, good 9, fair 4, poor 2, not evaluable 1). Subjective and objective symptoms, hematological biochemical data, and renal functions were checked up before and after administration of CCL. No side effect was observed.

View full abstract

Laboratory and clinical studies on cefaclor were performed with the following results.
1) The peak MIC value of cefaclor against Haemophilus influenzae was 6.25μg/ml and the antibacterial activity of cefaclor was two times higher than cephalexin (CEX). The peak MIC value of cefaclor against Klebsiella pneumoniae was 0.78μg/ml and the antibacterial activity of cefaclor was four to eight times higher than CEX.
2) Synergistic effect was observed in vitro by the administration of cefaclor together with gentamicin (GM).
3) Cefaclor 500mg was administered orally without meal to three patients and their serum peak concentrations were 15.7μg/ml, 14μg/ml and 7.4μg/ml respectively. On the other hand, the prolongation of the time to reach the peak level and the decreasing of the peak values were observed when it was administered with meal.
4) Cefaclor was administered to 30 cases of infections disease in total, including respiratory tract infection, acute cystitis, cholecystitis and diabetic gangrene and its clinical effect was evaluated. In respiratory tract infection, 8 of 18 cases showed excellent or good response. In acute cystitis 7 of 9 cases revealed excellent or good response and one case of acute cholecystitis showed excellent response. Diabetic gangrene was treated in two occasions with poor effect.
5) In one case Al-Pase elevated transiently. It returned to normal value by the cessation of the medication.
6) Cefaclor was evaluated to be a useful antibiotic if it is administered at a suitable dosage and by a suitable way comparing to the prevailing oral cephalosprins.

View full abstract

Cefaclor (CCL), a new oral cephalosporin, was administered to 18 children with various infections. The efficacy rate was 77.8%. CCL was effective especially for infections caused by E. coli, P. mirabilis and S. aureus, and in a case of urinary tract infection caused by Enterobacter cloacae.
Side effect was observed only in one case whose serum GOT and GPT were both elevated but were normalized after discontinuation of CCL for 6 days.
A 15 years old boy with chronic tonsillitis was administered 500 mg of CCL every 8 hours, and his tonsillar level of CCL was determined at tonsillectomy. The tonsillar level of CCL was 8.0 μg/g at 2 hours after administration of CCL.

View full abstract

Clinical application of the semi-synthesized cephalosporin, cefaclor (CCL), led to the following results,
1) CCL was administrated in 221 cases, acute pharyngitis 170, acute purulent tonsillitis 9, acute bronchitis 14, pneumonia 2, purulent lymphadenitis 6, UTI 2, eyelid abscess 1, and none-indication diseases 17. Excluding 17 cases of non-indication diseaes, clinical efficacy was evaluated in 204 cases. The effect of the drug was considered good in 179, poor in 10 and not ditermined in 15. The effective rate was 94.7%.
2) The pharyngeal microorganism was observed before and after CCL administration. The eradication rate of organism was 18/26 (69.2%) in S. aureus, 7/11 (63.6%) in S. pneumoniae, 4/4 (100.0%) in A-group S. hemolyticus and 11/25 (44.0%) in H. influenzae.
3) Side effect
Diarrhea was observed in 7 cases and nausea was observed in 1 case. No abnormalities on laboratory findings were noted.

View full abstract

Cefaclor, a new orally administrable cephalosporin, was evaluated fundamentally and clinically in children and following results were obtained.
(1) Serum levels of orally administered cefaclor were measured and, revealed a prompt rise and fall with a half life of 20-50 minutes.
Maximal serum level was obtained 30 minutes after administration and was 16.5 μg/ml by a single oral dose of 25 mg/kg of body weight.
Following serum concentrations of cefaclor were one hour, 11.2μg/ml, 2 hours, 2.27μg/ml, 4 hours, 0.77μg/ml and 6 hours, 0.2μg/ml respectively.
(2) Maximal serum concentration was lower than that of cephalexin (CEX). This might be the result of relative unstability of cefaclor compared with CEX.
(3) Clinical evaluation was done in 31 cases, consisting of 18 cases in upper respiratory infection, 8 cases in bronchitis and bronchopneumonia, 3 cases in urinary tract infection and 2 other cases. The results of 29 out of 31 cases were excellent and good clinically.
(4) Among 16 cases, in which pathological microorganisms were isolated from their throat or urine, 14 cases (88%) revealed good responses bacteriologically.
(5) According to these results, it was suggested that cefaclor is more effective on respiratory and urinary tract infections with lesser side effects than CEX is, and useful in pediatric field.

View full abstract

Cefaclor was evaluated on laboratory and clinical studies and following results were obtained.
1) Serum levels
Cefaclor was orally administerted in 25 patients to explore dose and influence of food. On our studies, dose response of the serum concentration was apparently observed and the serum concentration in fasting appeared higher than that with food.
2) Urinary recovery
On our studies in 3 patients, urinary recovery rates were 74.9, 76.3 and 79.0% within 8 hours.
3) Clinical results
Cefaclor was studied in 26 cases, (Bronchopneumonia 3, acute bronchitis 5, puruent lymphadenitis 1, angina lacunaris 13, angina catarrhalis 3 and acute urinary tract infection 2).
Clinical efficacy was 92.3% and bacteriological efficacy rate was 71.4%. No side effect was observed and abnormal laboratory finding was not noted.

View full abstract

Fundamental and clinical studies on cefaclor (CCL) were carried out and following results were obtained.
1) Minimal inhibitory concentrations (MIC) of CCL and CEX against 20strains of group A β-Streptococcus recently isolated from scarlet fever ranged from 0.05μg/ml to 0.78μg/ml and 0.10 μg/ml to 3.12μg/ml at 10⁶/ml inoculum size, respectively.
2) Blood levels of CCL after single oral administration of 10mg/kg were 4.4-4.6 μg/ml at 30 minutes, 2.8-3.4μg/ml at 1 hour and trace at 6 hours.
Urinary excretion rate of CCL was 66.6-82% within 6 hours.
3) CCL was administered around 20-30mg/kg/day to 33 pediatric infections including 6 cases with acute tonsillitis, n cases with, angina lacunaris, 12 cases with scarlet fever and 4 cases with other infections. Good clinical and bacteriological response was obtained in all cases.
4) No abnormal findings was observed after multiple administration of CCL.
5) On the basis of this study, adequate dosage regimen of CCL against mild or moderate infections was considered to be 20-30 mg/kg/day devided in 3-4 times per day.

View full abstract

Cefaclor (capsules, dry syrup), a new oral cephalosporin, was clinically evaluated in the field of pediatrics.
1. Antibacterial activity: Sensitivity of cefaclor was compared with that of cephalexin against the bacteria isolated from clinical specimens. Sensitivity of cefaclor was superior to that of cephalexin against Beta Streptococcus and H. influenzae, and similar to that of cephalexin against Staphylococcus aureus and Salmonella Group B.
2. Serum level and urinary excretion: Serum level of cefaclor reached the peak at 1 hour after the oral administration and became very low at 4 hours when cefaclor was given at 3 hours after a meal. Urinary recovery of the drug was 50% at 2 hours after the administration and 60% at 6 hours.
3. Cefaclor was administered to 32 pediatric patients with acute infections and showed excellent effectiveness in 18 cases, good in 11 and fair in 2 with a failure in one case. Effective results wer obtained in 90.6% of the total cases.
4. No adverse effect was observed. No abnormality due to cefaclor was seen in clinical laboratory studies.

View full abstract

Absorption and urinary excretion
Cefaclor (CCL) was administered orally 30 minutes after breakfast at a dose of 10mg/kg to 3 children and 20mg/kg to 2 children. After a 10mg/kg dose, mean serum levels were 4.1, 4.4, 0.9, 0.5 and 0.3μg/ml at 0.5, 1, 2, 4 and 6 hours, respectively, with a mean urinary excretion of 37.1% for the initial 6 hours. After a 20mg/kg dose, mean serum levels were 7.2, 6.1, 4.1, 0.4 and 0.1μg/ml at 0.5, 1, 2, 4 and 6 hours, respectively, with a mean urinary excretion of 30.9% for the initial 6 hours.
Clinical studies
CCL was administered to 52 pediatric patients with various acute bacterial infections (acute rhinopharyngitis 2, acute purulent tonsillitis 9, acute bronchitis 11, pneumonia or bronchopneumonia 11, acute urinary tract infection 5) at the dose of 25.5-56.8mg/kg/day for 3-10 days. The overall clinical response was excellent in 24, good in 26 and fair in 2. The rate of satisfactory clinical response (excellent and good) was 96.2%.
S. pneurnoniae was eradicated in 4 out of 5 cases, S. pyogenes in 2 out of 2, S. aureus in 4 out of 5, S. epidermidis in 1 out of 1, and H. parahaemolyticus in 3 out of 3. H. influenzae was eradicated in 4 and reduced in 5 out of 11 cases.
No side effects or abnormal laboratory findings were observed except diarrhea noted in 3 cases of suckling infants during therapy.

View full abstract

Cefaclor (CCL), a newly developed cephalosporin derivative, was examined basically and administered to the patients with acute infections. The results were obtained as follows:
1) Thirty one children with angina catarrhalis (2), acute laryngitis (1), angina lacunaris (12), scarlet fever (2), acute bronchitis (7), acute vaginitis (1), acute urethritis (2), acute pyelonephritis (1), acute cystitis (2), chronic pyelonephritis (1), were given orally 40mg/kg of CCL for 3 to 13 days. Clinical effective rate was 86.7%.
2) Adverse reaction was noted in one patient showing slight elevation of S-GOT.
3) Minimal inhibitory concentrations of CCL against total clinically isolated strains, such as S. aureus (3), S. epidermidis (1), Group A β-Streptococcus (3), S. pneumoniae (2), S. faecalis (3), E. coli (3), H. influenzae (3), K. pneumoniae (3), E. cloacae (2), P. maltophilia (1), were determined by the standard method of Japanese Society of Chemotherapy and compared with those of CEX. In most susceptive strains, especially in H, influenzae, E. coli, K pneumoniae, S. pneumoniae, S. aureus, MICs of CCL were more active than those of CEX.
4) The peak blood level of CCL at 1 hour after a single oral dose (20mg/kg) was 18.5 g/ml (average).
5) The excretion rate of CCL in the urine was 86.4%(average) up to 6 hours.

View full abstract

The authors have carried out the laboratory and clinical studies of cefaclor (CCL). The results were as follows;
The sensitivity was measured by plate dilution method on 32 strains of S. aureus, 14 strains of E. coli, 15 strains of K. pneumoniae isolated from patients. The distribution of sensitivity of S. aureus was 0.78-6.25μg/ml and the peak of distribution was 3.13μg/ml. Cefaclor inhibited the growth of all strains of S. aureus at less than 6.25μg/ml.
And the peak of distribution of sensitivity of E. coli was 25μg/ml. The growth of 66.7% of K. pneumoniae was inhibited in concentration of less than 6.25μg/ml.
Cefaclor were given orally at close of 10 mg/kg body weight to 3 children in granules, 2 children in capsules. The serum levels of cefaclor were 10.9, 3.9 and 1.4μg/ml at 0.5, 1 and 2 hours after administration in the group of granules, respectively, 6.95, 5, 3 and 2.3μg/ml at 0.5, 1 and 2 hours in the group of capsules, respectively, and the level at 4 hours was not detected. The urinary excretion rates were 57.3% in the group of granules, 58.2% in the group of capsules respectively, up to 8 hours after administration.
Cefaclor were applied to 16 cases with tonsillitis, 9 cases with UTI, 1 case each with scarlet fever and bronchitis, totalling 27 cases. And cefaclor were given 400 mg-1, 500 mg daily for 3-12 days. All cases were effective clinically.
No side effects were observed except for 1 case with elevation of GOT and rash, respectively.
Phagocytosis was determined by QUIE'S method. Phagocytosis of E. coli and K. pneumoniae by lucocytes was more enhanced in the presence of 1 MIC for cefaclor than 1 MIC for cephalexin at 4 hours after incubation.

View full abstract

Fundamental and clinical studies were made on cefaclor, a new oral cephalosporin, and the following results were obtained.
1) MICs were compared with those of cephalexin on the following clinical isolates: 14 strains of Staphylococcus aureus, 9 strains of Escherichia coli, 42 strains of Klebsiella pneumoniae biovar. oxytoca, each 3 strains of Klebsiella pneumoniae and Salmonella typhi, each 1 strain of Salmonella B group Proteus mirabilis, and Proteus morganii, 5 strains of Enterobacter and 8 strains of Pseudomonas aeruginosa. With each 10⁸/ml of Staphylococcus aureus and Escherichia coli, cefaclor had a higher MIC against a number of strains. However, with 10⁶/ml of each inoculum, cefaclor had almost equal and higher antibacterial activity against Staphylococcus aureus and Escherichia coli, respectively. Bacterial strains which showed less sensitivity to cefaclor than to cephalexin with the number of organism at 10⁸/ml were resistant to ampicillin. A similar tendency was noted in the case of Klebsiella pneumoniae biovar. oxytoca. Cefaclor was definitely more potent than cephalexin against Klebsiella pneumoniae, Salmonella and Proteus mirabilis. Both drugs showed almost no antibacterial activity against Proteus morganii, Enterobacter and Pseudomonas aeruginosa.
2) Cross over tests in absorption of dry syrup of cefaclor and cephalexin were performed in rabbits. Peak blood concentration after a single oral administration of 100mg/kg was lower than that of cephalexin, but there were noted the following trends with cefaclor, which include a shorter time required to attain the peak value, a longer half-time of decrease of blood level and a larger area under curve. When a single oral dose (10 mg/kg) of cefaclor was given to three children before meals, its blood concentration was maximum at 30 min. after administration, i. e., 7.6-10.6μg/ml (average: 9.6) and was too low to be detected in 2 hours. Urinary recovery rate up to 6 hours ranged from 37.2 to 82.0% with an average value of 62.5%. In one patient who received 29.9 mg/kg orally, the blood concentration was at its peak at 1 hour, i. e., 26μg/ml, 11.6 μg/ml at 2 hours, and undetectable at 4 hours. Urinary recovery rate up to 6 hours was 36.3%.
3) The following 28 patients with acute bacterial infections were treated for 3 to 10 days with an oral administration of cefaclor, 26.1-51.2mg/kg/day, divided in 3 to 4 doses: tonsillitis (18 cases), otitis media (2), sinusitis (1), cervical lymphadenitis (1) and pyelonephritis (6). The overall efficacy rate was 96.496: excellent in 17 cases and good in 10, and failure in a case of sinusitis. No clinical adverse reactions were noted. Transient elevation of GOT and GPT was noted in 3 patients.
4) Flavor and odor of cefaclor appeared to be well palatable to children.
5) Based on the above results, cefaclor is considered to be a potent new antibiotic in the treatment of bacterial infections in children and a favorable clinical response is expected with the dosage of 40mg/kg/day divided in 3 to 4 doses.

View full abstract

Cefaclor (CCL) is a new oral cephalosporin antibiotic. The serum levels and the rate of urinary excretion, the antibacterial activity and clinical effects of granules of CCL were investigated. CCL was given orally at dose of 10 mg/kg 1 hour after meal to 2 cases of 8-year-old male children, and serum levels and urinary excretion of CCL were measured. The peak value of levels were showed 6.3μg/ml and 4.3μg/ml at 30 minutes and 1 hour after administration to 2 cases, respectively, and serum concentration were showed 2.9μg/ml and 2.6μg/ml at 4 hours after administration to 2 cases, respectively. And the rate of urinary excretion was avarage of 60% during 6 hours.
The in vitro antibacterial activity of CCL and cephalexin (CEX) against clinical isolates of S. aureus and E. coli were compared using 10⁸ cells/ml and 10⁶ cells/ml inoculum size. Antibacterial activity of CCL against S. aureus was similar to CEX in 10⁸ cells/ml inoculum size. With 10⁶ cells/ml inoculum size, MIC of 1.56-3.12μg/ml for CCL and 3.12-6.25μg/ml for CEX were distributed in the range of 80% and 90%, respectively, and CCL was very superior to CEX. With 10⁸ cells/ml inoculum size of E. coli, MIC of 3.12-6.25 g/ml for CCL and 12.5μg/ml for CEX were distributed in the range of 56%, respectively.
On other hand with 10⁶ cells/ml inoculum size of E. coil, MIC of 1.56-3.12μg/ml for CCL and 6.25μg/ml for CEX were distributed in the range of 75% and 85%, respectively, and antibacterial activity of CCL againstE. coil was very superior to CEX together of both inoculum size.
CCL was administered orally to 32 patients of urinary tract infections in avarage dose of 36 mg/kg/day for 15 days, and rate of clinical effects and bacteriological effects were obtained 93% and 96%, respectively.
CCL was administered orally to 13 patients of other infections in avarage dose of 57mg/kg/day, and all cases were effective clinically, however bacteriological effects were unknown in all cases.
No abnormality was revealed by the clinical examination in either the blood picture or hepatic and renal function, except leukopenia and slight elevation of LDH in 1 case.
And these results demonstrated that the treatment of CCL is very effective in the field of pediartrics to urinary tract infection, upper respiratory tract infection and soft tissue infection.

View full abstract

Cefaclor for oral administration was given to 36 patients with acute or subacute infectious diseases; 25 cases were outpatients and 11 patients were hospitalized ones. They were 10 acute mastitis, 10 acute peritonitis with perforate appendicitis and 1 cecal perforation and 16 patients with infectious diseasesof soft tissue and skin.
The clinical evalution of results was classified to excellent in 17 cases, good in 16, fair in 3 and poor in none, the overall effective rate was 91.7 percent.
Any adverse effect was not recognized except one case of postoperative abscess of abdominal wall with fistula. In this case, the increase of GOT and GPT which was cured without any special treatment was observed. Moreover, at the second trial for the same patient with twice as much of the dosage and the duration, the same adverse effect was not developed.

View full abstract

Basic and clinical studies were conducted on cefaclor (CCL) and the following results were obtained.
1) Antibacterial activity
CCL showed antibacterial activity in vitro higher than cephalexin (CEX) but lower than cefatrizine (CFT) to gram positive organisms and gram negative bacilli except for Strep. faecalis, B. cereus, Proteus morganii and Ps. aeruginosa. Its antibacterial spectrum was similar to that of CEX and CFT.
2) Antibacterial activity to clinical isolates
CCL showed antibacterial activity to clinical isolates of Staph. aureus, E. coli, Klebsiella and Proteus mirebilis. Its MIC to Staph. aureus was lower than that of CEX and cephradine (CED) by one to two-fold dilutions but higher than that of CFT by one dilution.
Its MIC to E. coil, was similar to that of CFT and somewhat lower than that of CEX, CED, CET and cephapirin (CEP). To clinically isolated Klebsiella and Proteus mirabilis, CCL showed the best antibacterial activity of all the cephalosporin antibiotics currently in use.
3) S'erum and urinary levels
S'erum and urinary levels of CCL after oral administration of a 500mg dose were determined by cupplate method using M. luteus ATCC 9341 as a test organism.
S'erum level reached a peak (mean 9.05μg/ml) 30 minutes after administration. Urinary level reached a peak (mean 3790μg/ml) one hour after administration. Mean urinary recovery up to 6 hours was 72.8%.
4) Pharmacokinetics
Pharmacokinetic parameters were calculated with a computer using the one compartment open model method. Ka was 4.36 hr^-1. Kel 0.709 hr^-1, Vd 39.04 L, T% 58.66 min., t-max 0.5 hr and C-max 9.00μg/ml.
5) Metabolism in human subjects
Metabolism of CCL was examined with urine of human subjects after CCL administration. With UV and bioautogram, identical CCL and a metabolite having an antibacterial activity were recognized on TLC.
6) Tissue distribution
CCL levels in various organs were examined after a 20 mg/kg dose each of CCL to 3 SD rats. CCL level was the highest in the kidney, followed by serum, spleen, lung, heart, liver and muscle. CCL was not detected in the brain.
7) Clinical results
CCL was administered to 33 patients with various surgical infections. Clinical response was satisfactory in 30 cases (90.9%) and failure in 3 cases. As to adverse reactions, skin rash developed in one case after CCL therapy. However, it was not clear if the rash was due to CCL or not.

View full abstract

Cefalor, a new cephalosporin, was orally administered to 29 cases of surgical infections and 2 cases for prophylaxis of postoperative infections.
The daily dose was ranged from 750 mg to 1.5 g, and the maximal dose and duration were 19.5 g and 13 days respectively.
The overall effective rate in surgical infections was 75.9%. Transient elevation of seram transaminases was observed in one patient, but no adverse effects were noticed in the others.

View full abstract

Clinical studies of cefaclor, a new oral cephalosporin, were carried out in a total of 20 patients with various infections and following results were obtained.
Cefaclor was administered in daily dose of 750 mg for 3 to 27 days. Good clinical response was obtained in 16 out of 18 cases with skin and soft tissue infections (SSTI), and poor results in 2 cases with choledochitis after choledochostomy.
Bacteriologically, three strains of S. aureus and 1 strain of S. epidermidis isolated from SSTI were eliminated after cefaclor therapy, but 1 strain of S. aureus from SSTI, 2 strains of K. pneumoniae from choledochitis and Enterobacter plus K. pneumoniae (mixed infection) from abcess were unchanged.
As for side effect, transient anorexia was observed in 2 cases.

View full abstract

Laboratory and clinical studies were conducted on cefaclor (CCL).
The in vitro antibacterial activity of CCL and cefalexin (CEX) against 40 clinical isolats of Staphylococcus aureus and Escherichia coli was compared. The inoculum sizes were 10⁸ and 10⁶ cells/ml. Especially CCL appears to be more active on the 10⁶ cells/ml than CEX against both strains. CCL inhibited 60% of Escherichia coli at 1.56μg/ml and 95% at 3.13μg/ml. To achieve similar levels of activity, 12.5μg/ml of CEX was required. Against Staphylococcus aureus, 1.56μg/ml and 3.13μg/ml of CCL inhibited 55% and 80% of the strains. To achieve the same levels of activity, 6.25μg/ml of CEX was needed.(The results mentioned above were obtained from the condition of inoculum size of 10⁶ cells/ml).
One of the 23 cases treatment was unachieveable because of nausea. The treatment was successful in 16 patients out of 22 patients.

View full abstract

Fundamental and clinical studies of cefaclor (CCL) was done in the surgical field and following results were obtained.
1) Antibacterial activity
Antibacterial activity of CCL, cephalexin (CEX) and ampicillin (ABPC) to S.aureus, S. epidermidis, E. coli and Klebsiella were examined and CCL was proved to be equal or more potent than CEX and ABPC is.
2) Absorpsion
Cefaclor (500mg) was administered once at fasten in three adults, and the mean peak serum level was 10.15μg/ml after 1 hour.
3) Clinical results
Cefaclor was administered to twenty-two patient with surgical infections, and the clinical responces were excellent in 5 cases, good in 13 and poor in 4. No side effects could be found.

View full abstract