Pharmacological effects of clindamycin on respiration, blood pressure, and excised organs (heart, intestine and blood vessels) of animals were studied. The drug minimum concentrations (on ave rage) effective on the movement of various excised organs were determined. The results obtained were: deceleration of the toad heart at 10^-3 g/ml, deceleration of the guinea pig atrium at 2 x 10^-5 g/ml, acceleration of the rabbit intestine at 10^-6 g/ml and its deceleration at 10^-4 g/ml, deceleration of the guinea pig intestine at 10^-4 g/ml, and dilation of the rabbit ear vessels at 10^-5 g/ml. In the rabbit, a fall of blood pres sure and a respiratory deceleration were noted at the dosage levels of 5 mg/kg and 10 mg/kg, respectively, but no change in electrocardiogram was observed even at 20 mg/kg.

View full abstract

Bacteriological study on clindamycin, a new derivative of lincomycin, was performed. Clindamycin showed an antibacterial spectrum approximate to that of lincomycin, but the in vitro antibacterial activity is 2 to 4 times more potent. This was also applicable to the strains of clinically isolated Staphylococcus aureus tested. Novertheless, a complete bacterial cross-resistance was observed between clindamycin and lincomycin.
Clindamycin was also cross-resistant with the majority of the macrolides, though not with erythromycin in some cases. Clindamycin demonstrated a same te ndency as lincomycin regarding the stability of its aqueous solution and in the tests of the effect of pH and microbic inoculum size on its bacteriostatic activity. Only it bound slightly more easily to serum protein than lincomycin. The in vitro development of bacterial resistance to clindamycin was gradual as was the case with lincomycin.
As compared with lincomycin, clindamycin proved to be far more antibacterial in vivo, as was in vitro, in the treatment of mice experimentally infected with Staphylococcus aureus, Streptococcus hemolyticus; or Diplococcus pneumoniae.

View full abstract

A total of 298 strains of recently isolated pathogens, i. e. Staphylococcus aureus, hemolytic streptococci, pneumococci, enterococci, Haemophilus, Escherichia coli, Klebsiella, Pseudomonas, and several species of anaerobes were tested for their in vitro susceptibility to clindamycin and lincomycin by a plate dilution method.
Both clindamycin and lincomycin are effective in vitro to gram-positive cocci and anaerobes but not to gram-negative bacilli, especially Escherichia coli, Klebsiella and Pseudomonas. For almost all species of tested pathogens clindamycin was more effective than lincomycin.
Inhibitory effect of clindamycin and lincomycin for 2 strai ns of Escherichia coli was much increased in alkaline medium (pH 9).

View full abstract

1. Clindamycin had an excellent antibioti c activity on clinically isolated staphylococcal strains sensitive to lincomycin.
2. Of gr o up A staphylococci resistant to macrolide antibiotics, those strains sensitive to lincomycin were highly susceptible to clindamycin.
3. Of A group staphylo c occi, those highly resistant to lincomycin were equally resistant to clindamycin.
4. Growth of group C staphylococcal strains, which account for the majority of the staphylococcal orgainsms resistant to macrolide antibiotics, could be inhibited by clindamycin with lower concentration than that of lincomycin, despite the fact that resistance of these strains to macrolide antibiotics and lincomycin may be induced by erythromycin or oleandomycin.
5. Comparative study using various variants of g roup C staphylococci resistant to macrolide antibiotics proved the superiority of clindamycin over lincomycin in the antibiotic activity on any variant tested.

View full abstract

A new antibiotic, clindamycin was studied bacteriologically and clinically, with the results which may be summarized as follows:
1) In a study with t he agar-dilution method on a total of 109 strains of 19 bacterial species, Staphylococci, β-hemolytic Streptococci, α-hemolytic Streptococci, Pneumococci and Corynebacterium diphtheriae were found to be markedly susceptible to the agent, showing their MICs of 0. 19 pg/ml or less.
2) With the view of preparing grounds for application of the single-disc method to the sensitivity test in clinical laboratory, graphic analysis of the dose-response data concerning interrelations between. the MIC values and the diameters of inhibition zones were conducted on each of 1) conventional (overnight: about 16 hour) assay, ii) delayed (about 24 hour) assay for slowly growing bacteria, iii) 4-hour rapid assay with heavy inocula, and iv) 6-hour rapid assay with heavy inocula.
Experimental errors inherent were also studied in comparison with the ones in the 2-fold agardilution method.
3) By the thin-layer cylinder-plate assay technique using Staphylococcuesp idermidis ER-2 as a test organism, the concentration of the agent was assayable to the lower limit of 0. 03μg/ml.
Following a single oral administration of 300 mg clindamycin, serum peak levels of 2∼4μg/ml were. obtained at 1∼4 hours, with a persistence of serum levels at least 0. 3μtg/ml over ensuing 10 hours. After the oral administration the urinary recovery was found to be about 20% within 24 hours.
4) Treatment with clindamycin was reasonably effective in each one case of subacute bacterial endocarditis and bronchopneumonia.
5) Any side-eff ects on the digestive tract associated with the oral administration of the agent were not observed. There was no apparent evidence of hepatic or renal functional impairment in the two patients administered orally the agent at a dose of 180 mg for 33 days and at a dose of 90 mg for 20 days.

View full abstract

On clindamycin, fundamental experiment and clinical application were performed.
1. The minimal inhibitory concentrations of clindamycin against 160 st r ains of Staphylococcus aureus -were mainly in the range of 0. 063∼0. 125 mcgfml. These values were one half to one eighth of those of lincomycin, but 9 strains resisted to 100 mcg/ml of both clindamycin and lincomycin.
2. The blood peak levels and half life times of clindamycin at oral dose of 300 mg were little influenced by renal impairment.
3. Six cases of acute respiratory infections including 3 cases of pneumonia, 1 case of bronchopneumonia and 2 cases of primary atypical pneumonia were treated with daily oral dose of 600 mg of clindamycin. This drug was effective in all cases. In one of these cases, serum transaminase elevation i(GPT 240 units, GOT 80 units) was found with eosinophilia and liver swelling between the third and fourth week of administration.

View full abstract

Summarized below are the results of our laboratory and clinical studies of clindamycin. 1) Staphylococcal strains tested were found to be 2 to 8 times more susce ptible to clindamycin than to lincomycin. On the other hand, clindamycin was found to have poor antibacterial activity on Gramnegative bacilli.
2) The bloo d level, determined using either Streptococcuse hmolyticusCook or Sarcina lutea PCI 1001 as the test organism, resulted about same. The blood level 2 hours after oral administration of 150 mg was 0. 7 mcg/ml on the average when phosphate buffer was used for preparation of clindamycin standard solution. It was 1. 5 mcg/ml when serum was used.
The 6-hour urinary recovery in 2 patients was 7. 26 % and 7. 47% respectively (test organism: Streptococcus hemolyticus).
3) Effect of clindamycin on 2 cases of bronchiectasis and 1 case of chronic bronchitis was good in one (bronchietatic patient) and unknown in the other two.
GOT and GPT determinations did not show any particula r changes during the medication as compared with pre-treatment values.

View full abstract

I) Distribution of clindamycin (CLM) in rats:
a) Recovery from organ emulsions: T he recovery rates of in vitro added CLM from organ emulsions were farily well.
b) Concentrat i o n in organs: Concentrations of CLM (corrected by the recovery rates) in organs after oral administration were examined. The lung showed the highest concentration, whic h was characteristic of this antibiotic. The order of the concentration was: Jung>liver>kidney>spleen>muscle>blood>brain.
II) Biliary excretion in rabbits:
Intravenously injected CLM was excreted in much higher concentration into bile than the simultaneously assayed serum level, similarly to the other macrolides. The recovery of CLM from bile in 3 hours was 0. 5 to 0. 95%.
III) In vitro sensitivity of staphylococci against CLM:
Twenty-two strains of Staphylococcus aureus show e d M. I. C. under 0. 25 mcg/ml of CLM; while almost all (24 strains) of them showed M. I. C. of 0. 5 to 4 mcg/ml of LCM. Those staphylococci were found to be most sensitive to CLM among the antibiotics tested; i. e. CLM, LCM, erythromycin, olea ndomycin, triacetyl-oleandomycin, spiramycin, josamycin, tetracycline, doxycycline, kanamycin and kanendomycin.
IV) Blood levels in human adults:
Assays of the blood leve l s after cross-over oral dosage of 300 mg CLM or of 500 mg LCM were performed in 4 healthy human adults. The peak of the blood level was reached earlier by C LM (in 1 to 2 hours) than by LCM (in 4 hrs. ); moreover, the peak was much higher in the form er in spite of the smaller dosage (average: 5. 5 mcg/ml) than in the latter (1. 6 mcg/ml). Accumulatio n of the drug in blood was not observed during serial administrations of CLM (300 mg every 8 hrs. ) to 2 patients.
V) Urinary excretion in human adults:
In three of the above healthy human adults, urinary recovery rates of CLM were higher than those of LCM, excepting one person whose blood level of LCM was rather high. The urinary r ecovery rates of CLM were 7. 5 to 16. 4% in 24 hours.
VI) Clinical trials:
Five cases ( 1 pneumonia, 1 tonsillitis, 2 chronic bronchitis and I lymphadenitis) were successfully treated with CLM (600 to 900 mg daily). No marked adverse effects were observed.

View full abstract

Clindamycin, a lincomycin derivative recently developed at the laboratories of the Upjohn Company, U. S. A., has been evaluated at our hospital to obtain the following results.
1. Clindamycin was cross-resistant with lincomycin in coagulase- positive staphylococci. In the same staphylococcal strains of lower M. I. C., however, clindamycin was superior in antibacterial activity to lincomycin, also somewhat to erythromycin.
2. In absorption and excretion, clind amycin was by far better than lincomycin. The fact that a single oral administration of 300 mg of clindamycin attained a blood level higher than 3. 0 mcgiml suggests that 300 mg twice a day would be a sufficient daily regimen with this antibiotic. Average 17. 7% of clindamycin urinary recovery within 24 hours after a single oral dose of 150 mg indicates usefulness of this agent for treatment of urethral infections. Clindamycin concentration in cerebrospinal fluid was determined as 0. 13 mcg/ml in one meningitis patient given oral doses of 600 mg three times a day.
3. Clindamycin resulted effective in 11 (69%) of 16 cases of various infections treated as a rule with oral doses of 600 mg a day. Excellent response was observed in one patient with colibacillary urethral infection.
4. No particular side effects were observed.

View full abstract

1) In the sensitivity test of Staphylococcus aureus isolated from patients using plate dilution method, 48 strains were found to be less than 0. 8 mcg/ml in M. I. C. and 11 strains to have natural resistance. Lincomycin is found to be less active than clindamycin and to have cross-resistance with it.
2) In absorption and excretion study of clindamycin following 150 mg oral dose in hum an subjects, a sustained blood level (maximum 0. 6 mcg/ml) and poor urinary recovery (5. 7% of dose in 6 hours) were observed.
3) In urinary and biliary excretion study in dogs, low but prolonged blood level and low urinary and biliary output were observed following 5 mg/kg intravenous administration. Values worked out through the study are as follows: half-life in blood 3. 1 hours, volume of distribution 2. 5 I/kg, renal and biliary clearance 0. 7 and 0. 05 ml/min/kg, and rates of removal from kidney and bile 0. 02 and 0. 001 respectively.
4) In tissue distribution study in the rats, higher tissue concentrations than plasma level were found 1, 3, and 5 hours after 20 mg/kg intramuscular dose. Five hours after intravenous dose in dogs, the amount of the substance in extravascular space was estimated at 85% of dose. In both study, concentration of the antibiotic was found to be highest in the lung tissue.
5) In in vitro degradation study in the rat, clindamycin seems to be inactivated more slowly than lincomycin.
6) In protein binding study using cellophane bag dialysis, low binding rate with bovine serum was observed.
7) In preliminary studies on metabolism of clindamycin, one hour blood level of rats with 80 mg/kg phenobarbital pretreatment is higher than those without treatment, and in vitro inactivation study showed the activity in the liver of rat treated as above is less decreased than those non-treated. These studies seem to indicate that clindamycin is metabolized more rapidly to the more active demethyl metabolite in rats pretreated with phenobarbital.
8) Toxicological study of cl i ndamycin in rats was carried out. Following intraperitoneal injection of 100 mg/kg/day for 7 days, histological study showed slight changes in the liver with clindamycin and lincomycin but not in the kidney. There were no significant changes in values of SGPT and SGOT of rats.
9 ) Clinical observation in 20 cases with respiratory infections treated with daily 600 mg oral dose showed 8 excellent, 10 good, and 2 poor results. There were no side-effects with the exception of a possible case with skin rash and nausea.

View full abstract

The following is the report summary of our laboratory and clinical studies of clindamycin (7?chlorolincomycin).
1. Staphylococcal strains isolated in our hospitals in 1968 from patients with respiratory infections were found to be about 4 times more susceptible to clindamycin than to lincomycin, but cross resistance was observed between these two agents.
2) The tissue concentrations of clindamycin orally administered in rats were highest in lung and liver, then in kidney, and lowest in blood. Clindamycin remained longest in lung.
3. Comparative treatment of mice experimentally infected with SMITH strain of Staphylococcus revealed apparent superiority of clindamycin over lincomycin in effectiveness.
4. Oral administration of clindamycin, 600 mg divided in 4 doses daily, in 22 cases mostly of acute respiratory infections such as acute bacterial pneumonia and infectious asthma had sufficient therapeutical effect as long as the causative organisms were sensitive to this antibiotic.
5. Side effects requiring discontinuation of the clindamycin therapy developed in none of the patients treated with this agent. Significant increase in GOT and GPT, however, was observed in one patient with somewhat high pre-treatment values.
Gastrointestinal disturbance developed in t wo patients but disappeared while they were on medication. No abnormal changes were observed in urinary determinations and hemogram of the patients tested.

View full abstract

1. The sensitivities of 51 strains of Staph. aureus, 12 strains of Strept. viridans and 16 strains of Strept. hemolyticusfo r clindamycin were measured by plate dilution method. The strains, which indicated less than 0. 4 mcg/ml were 32 among 51 strains of Staph. aureus. However, 10 strains indicated not less than 100 mcg/ml of MIC. MIC of all strains of Strept. hemolyticus was less than 0. 2. mcg/ml. MIC of Strept. viridans were ranged from 0. 2 to 25 mcg/ml.
2. The average blood levels by an oral ad ministration of 300 mg of clindamycin were 1. 65 mcgiml after 1 hour, 1. 5 mcg/ml after 2 hours and 0. 7 mcg/ml after 6 hours. The average urinary recovery was 9. 0% in 24 hours.
3. The therapeutic effect on the experimental Staphylococcal infection of mice was excellent.
4. The binding ratio to serum protein was measured by the ultracentrifuge method. The binding ratio was 71%.
5. Fifte en patients with various infectious diseases were treated by daily dosis of 600 mg of clindamycin. Eleven patients were improved, but 4 patients failed. The number of cases indicated side effects such as diarrhea, exanthema, epigastric discomfort and water brash was one, respectively.

View full abstract

1) In laboratory experiments, clindamyci n (CLM), like lincomycin (LCM), demonstrated a high antibacterial activity against gram-positive organisms, particularly Staphylococcus aureus. Though most of the organisms tested were not resistant to CLM, a tendency of bacterial cross-resistance was noted between CLM and LCM.
2) CLM showed to be 4∼8 times more antibacterial than LCM in vitro, and considerably high blood and urine levels were obtained in vivo.
3) In view of the above data and th e therapeutic results obtained with CLM, the clinical significance of CLM appears to be in that this drug can substitute for macrolide antibiotics with. better results or with a less dose.

View full abstract

Laboratory and clinical studies of clindamy cin were carried out with the following results:
1. The growth of approximately 66% of the Staphylococcuasu reus strains isolated from p athological specimens was inhibited at drug concentrations of 0. 78 mcg/ml and less. Clindamycin was evaluated 4-8 times more potent in vitro than lincomycin against this organism. The former also prov ed leading the latter in the activity against gram-negative bacilli, though all strains tested were resistant to clindamycin at the concentrations below 25 mcg/ml.
2. With a single oral dose of 150 mg, th e blood level reached the peak of 1. 8 mcg/ml on the average at 0. 5∼1 hr., and almost cleared out at about 6 hr. The urinary recovery rate in 6 hours was 12. 7% on the average.
3. Clindamycin was orally administered to 12 patients with a respiratory infection. The clinical response was excellent in 3 and good in 4. The rest had a gastrointestinal disturbance.

View full abstract

1. Sensitivity:
More than 3/4 of test strains of coagulase positive Staphylococcuws ere sensitive against clindamycin at the concentration below 0. 8 mcg/ml.
2. Blood level:
When administrated orally to normal adults, clindamycin showed higher blood level than lincomycin. When it was administered once at a dose of 300 mg, its blood level reached the peak (3. 25 mcg/ml) after 1 hour and reduced to 0. 87 mcg/ml after 6 hours. 3.
Excretion into urine:
The concentrat i o n of clindamycin in urine was low. Urinary recovery rate was 19. 75% in the first 8 hours. 4.
Tissue level:
Rat tis s ue assays showed that kidney had highest activity of clindamycin and other tissue were in the order of lung, liver, spleen, serum and so on.
5. Inactivation in rat liver:
Inactivation of clindam y cin by tissue of rat liver was stronger than lincomycin.
6. Clinical results:
Clindamyci n was administered to 14 cases of internal infections. Four cases of bacterial pneumonia and 6 cases of bronchitis were effective.
7. Side effects:
Only in two cases of the 14 cases given clindamycin, nausea and diarrhea were observed. In other 12 cases, no side effects were observed.

View full abstract

On a new lincomycin (abbreviated as LCM ) derivative, clindamycin or 7-chlorolincomycin (abbreviated as CLM) several experiments were carried out and the following results were obtained.
1. So-called sensitive Staphylococcuasu reus showed the smaller MIC values against CLM th an LCM at about three degree of plates in two-fold dilution method.
2. The difference between bactericidal and bacteri ostatic MIC values was zero to four grades.
3. CLM had no strong adsorption to red blood corpuscle. The serum protein binding r ate by means of cellophane bag dialysis was 60% on the average.
4. The peak serum level following oral admin istration of CLM to rabbits in dose of 100 mg per kg was 5 to 25 mcg/ml at 1 to 3 hours after starting. At cross over test of CLM and LCM, CLM showed considerably higher levels in each animal.
5. The peak organ level after oral administration of CLM to rats in dose of 50 mg per kg ranked in the order as lung, spleen, liver and kidney, each exceeding serum level.
6. The similar experiment to mice gave the same results as the above ones. The mixing with organ homogenates brought the reduction of CLM concentration of about 50% in that of liver, but was slight in other organs. Comparing with LCM oral administration, only kidney level was higher in this case, and CLM was always superior to LCM in other organ distribution.
7. The treatment of CLM against staphylococal subcutan eous infection to the back of mice showed more execllent effect than that of LCM or erythromycin.

View full abstract

Purpose of this paper is to describe clinical evaluation of clindamycin prescribed to 8 patients with various infectious diseases.
Patients treated were 2 of bacterial pneumonia, 3 of bronchitis, each 1 of bronchiectasis, subacute bacterial endocarditis (SBE) and purulent meningitis.
Patients were consisted of 4 males and 4 f emales and age of patient ranged from 15 to 70 year-old.
Clinical efficacy of clindamycin in bacterial pneumonia and bronchitis was good and i n purulent meningitis excellent but it was not effective in bronchiectasis and SBE.
Causative organism in bacterial pneumonia and bronchitis was normal inhabitant. Although clindamycin was sensitive to St. viridans isolated from SBE by disc method, clinicaly it was not effective.
Gram positive bacilla were isolated from purulent meningitis.
Dosage of clindamycin in bacterial pneumonia and b ronchiectasis was 600 mg q. i. d., and duration was varied from case to case. They were from 9 days to 32 days. SBE was treated with clindamycin 300 mg three times daily for 5 days. Bacteremia was disappeared but fever spiked up to 38°C frequently and no improvement of sed-rate was obtained. Clindamycin was increased to 1, 500 mg daily for 5 days. Even with this dosage, fever stayed to be high, and clindamycin was replaced by penicillin. In purulent meningitis, clindamycin of 300 mg three times daily for 14 days were prescribed. After 5 days, fever became normal and meningeal signs were disappeared.
No serious side effects were noted except meteorism in SBE who was treated by more than 900 mg and loose stool in purulent meningitis.

View full abstract

Most of the 90 strains tested of coagulase-p o sitive staphylococcal pathogens isolated from children with acute infections were sensitive to clindamycin, and their growth was inhibited at a drug concentration as low as 0. 2 mcg/ml. This may indicate clindamycin is 4∼8 times as potent as lincomycin. Nevertheless, there were a few strains resistant to clindamycin, and all of which also showed a crossresistance to lincomycin and macrolides. With a single oral dose, clindamycin level reached a higher peak more rapidly in blood and urine than in the case of lincomycin.
Clindamycin was administered to children with acute inf ections at the rate of 15∼20 mg/kg/day divided into 3 or 4 portions. The therapy was effective in 69. 2% of the patients treated. This was comparable to the results obtained in the previous clinical investigations with lincomycin. A relatively high incidence of gastro-intestinal troubles (19. 2%) was observed as a side effect, but they subsided upon suspension of the therapy. Whether or not prolonged clindamycin therapy might have some effect on the liver function has yet to be investigated, though such a sign was not recognized at all with the regimens we used this time.

View full abstract

A series of basic and clinical study on clindamycin was conducted at our institutions to obtain thefollowing results:
1) M. I. C. of clindamycin against Staphylococcusa ureus haemolyticusw as 0. 025 mcg/ml, or about 4 times as strong as lincomycin in antibiotic activity. Although most strains resistant to other antibiotics were susceptible to clindamycin, some were found resistant. Clindamycin was cross-resistant with lincomycin in these resistant strains.
2) M. I. C. of clindamycin again st Streptococcush a emolyticusw as 0. 025 to 0. 05 mcg/ml, or 10 times as strong as that of lincomycin.
3) Bor. pertussis, H. i nfluenzae, C or. d iph., Cor. xer., Dip. pnevm., Strep. faec., etc. were found more than twice as susceptible to clindamycin as to lincomycin.
4) In experimental mice with staphyloc occal infection, clindamycin could achieve the same therapeutical effect as lincomycin with one tenth dose of the latter. This indicates an apparent parallelism between in vitro and in vivo antibiotic activities of these two antibiotics.
5) A single 10 mg/kg dose of oral clindamycin to a child patient attained the highest blood level 1 hour after administration and sustained for 8 hours blood level effective to clindamycin sensitive organisms.
6) Therapeutical effect apparently due to clindamycin was observed in 30 out of 32 pediatric patients of 8 different infections. Good parallelism existed between the in vitro sensitivity of the causative organisms and the clinical effect in these patients.
7) The 10∼20 mg/kg/day clindamycin regim en continued for 8 days did not bring any symptoms, of gastrointestinal, hematological, hepatic, and renal dysfunctions.
(Part of this report was made public at the 16th gene r al meeting of Japan Society of Chemotherapy, May, 1968. )

View full abstract

The authors have carried out the clinical studies on clindamycin. The results were as follows; Sensitivity to clindamycin of 60 strains of Staph. aureus isolated from patients was determ ined by the plate dilution method. The growth of 50. 0% of all strains was inhibited in concentration of 0. 1 mcg/ml or less than 0. 1 mcg/ml. Clindamycin demonstrated in vitro antibacterial activity approximately 4 times of that with lincomycin.
Clindamyc in was given a single orale dose of 2. 5∼5. 0 mg per kg, b. w. to 3 children. The peak blood level was reached at 4∼6 hours respectively after administration. And the blood level at 12 hours after administration was 0. 09-0. 4 mcg/ml.
The excretion rate of clindamycin in the urine after a single orale dosing was 4. 5% up to 24 hours of period.
Clindamycin were used for 18 cases of infection of the upper respiratory tract. The treatment was effective in 5 of 8 cases receiving clindamycin in a daily dose of 8∼15 mg per kg, b. w. and in 8 of 10 cases receiving clindamycin in a daily dose of 16∼25 mg per kg, b. w.. Six patients exhibited the side effect of abdominal pain, anorex ia and rash.

View full abstract

The clinical response of children with beta hemolytic streptococcal infections to clindamycin was evaluated.
Twenty-seven (27) children with scarlet fever received oral clindamycin at the rate of about 20 mg/kg/ day divided into 3 portions for 5 consecutive days. Of them, 18 (66. 7%) showed good to excellent clinical response.
This result excelled those obtained with oral administration of biciilin-16/43 (37. 2%), erythromycin5/20 (25%), tetracycline-69/163 (42. 3%) and spiramycin-11/20 (55%), though it was outstripped by that of parenteral penicillin (300, 000 units I. M. )-80/92 (86%).
The rate of the effectiveness of the above clindamycin t herapy was 2/4 (50%) with a dosage level less than 20 mg/kg/day and was 16/23 (69. 6%) with this level or above. In view of this, it appears 20 mg/kg/day at least of clindamycin is to be used to obtain a better clinical result in the treatment of pediatric scarlet fever.
Clindamycin was also effective in 2 patients with hemolytic streptococcal infections. No side effect was observed in all patients treated.

View full abstract

1. The activity against 31 strains of Staphylococcus aureus, separated from pyoderma lesions, was studied. Six strains were cross-resistant against lincomycin and clindamycin. Clindamycin has stronger activity against the lincomycin-sensitive Staphylococcus strains.
2. The blood level in healthy human males after the oral administration of 300 mg reached the peak (2. 2∼1. 1 mcgiml) at 1 hour.
3. Clinical use of clindamycin was tried in 15 cases of pyoderma. Three hundreds mg of clindamycin wers administered 3 times daily. Several cases complained of slight stomach trouble. Complaint of diarrhea was absent.

View full abstract

Clinical observations were carried out in 27 cases with staphylococcal skin infections treated with clindamycin. The results were discussed by classifying the 27 cases into 3 groups, that is 17 cases of pyodermas, 8 cases of secondary infections and 2 cases of prophylactic application to posttraumatic infection.
Remarkable effects were obtained in 12 cases in the first group and also in every 2 cases of the third group, whereas no improvements were revealed in 4 cases in the second group, presumably in vitro resistance of their causative organisms against clindamycin in these cases are estimated as the cause of the results.
Untoward effects were observed in 2 cases, namely gastro-intestinal disturbances in the one, and heavy toxic eruption in the other.
The MICs of clindamycin by agar plate dilution methods were less than 0. 2 mcg/ml in 30, and more than 100 mcg/ml in 7 of 40 strains of Coagulase positive staphylococci.

View full abstract

Following results were obtained by our fundamental and clinical studies of clindamyc in (CLM).
1) The in vitro antibacterial activity of 7?LCM against 75 strains of staphylococci isolate d from boils and other skin infectious diseases was approximately 2-8 times than that of lincomycin (LCM). Comparing with erythromycin (EM), as to 9 resistant strains for EM, 5 of those were also resistant for CLM but other 4 strains were inhibited by 0. 2 mcg/ml of CLM.
2) CLM was not effective in the treatment of experimenta l rabbit syphiloma, though EM was remarkably effective.
3) CLM was clinically applied to 19 cases of skin infectious diseases. Effective therapeutic results were obtained in 13 of 19 cases. The cases without effect for CLM therapy were discussed and CLM in the treatment of pyoderma was appreciated.
4) No noticeable side effect was obser ved except one case complained a nausea.
5) Five cases of herpes zoster showed the considerable improvement throug h CLM administration were reported. Further study of CLM on herpes zoster may be required.

View full abstract

Clindamycin is a new derivative of lincomycin, Upjohn. Our clinical and laboratory study on the drug was summarized as follows.
Minimal inhibitory con centrations of clindamycin against Staphylococcus aureus 209p, NEwmAN, TERApmA and SMITH were all the same and they were 0. 05 mcg/ml, while those of lincomycin(LCM) were 1. 56 mcg/ml, 0. 8 mcg/ml, 0. 8 mcg/ml and 0. 8 mcg/ml. Several strains reserved at our laboratory resis ted 100 mcg/ml of both clindamycin and LCM.
The sensitivity distribution of co agulase-positive staphylococci cultured from surgical infections against clindamycin was a little different from that against LCM. High resistant strains of staphylococci were samely resistant against clindamycin as against LCM. However, among the strains sensitive or moderately resistant to LCM there were many strains sensitive to clindamycin.
Average serum concentration of clindamycin, when it was orally give n at 300 mg as a single dosis, was 0. 48 mcg/ml after 30 minutes, 1. 80 mcg/mi after 1 hour, 2. 65 mcg/m1 after 2 hours and we could assay 0. 8 mcg/m1 even after 6 hours. Comparatively to say, LCM that of LCM, orally given in 500 mg as a single dosis, was 0. 31 mcg/ml after 1 hour, 0. 34 mcg/ml after 2 hours, 1. 14 mcg/m1 after 4 hours, and we could assay 1. 02 mcg/m1 after 6 hours. Maximum serum concentration of clindamycin was 4. 56 mcg/ml, when it was given 600 mg as a single dosis.
The concentrations of clindamycin, if it was orall y given 300 mg as a single dosis were 28∼34 m cg/ml in the first 30minutes' urine, 67∼75 mcgiml in 30∼60 minutes' urine, 200 mcgfml in 1∼2 hours' urine, 210∼420 mcg/m1 in 2∼4 hours' urine and 50∼60 mcg/m1 in 4-6 hours' urine. Six hours' recovery rate of urine clindamycin was 15. 6%.
Seventeen cases of minor su rgical infections were treated with oral clindamycin. Daily dosis was 450 mg, 600 mg, 900 mg or 1, 200 mg for each. The results were excellent in 17. 6%, good in 70. 6% and failed in remaining 11. 8% of patients.
Two patients (11. 8%) complaine d of nausea, other one complained of nausea and poor appetite after take of the drug.

View full abstract

The following are the results obtained in our laboratory and clinical studies of clindamycin in surgical infections.
1) Forty-six strains of coagulase-positive Staphylococcus aureus isolated from surgical infections were tested for their susceptibility to clindamycin and lincomycin. Of them, 36 strains (78. 3%) were inhibited by 3. 13 mcg/ml or lower of clindamycin and 15 strains (32. 6%) by 3. 13 mcg/m1 or lower of lincomycin.
2) Study of correlation between clindamycin and lincomycin in antibacterial activity on 46 strains of Staphylococcus aureus demonstrated apparent cross resistance in 6 strains and superiority of clindamycin over lincomycin by 1 to 5 degrees in terms of two-fold dilution method in their antibacterial activity on the remaining 40 sensitive strains.
3) The clindamycin serum level attained the peak of 2. 56 mcg/ml 1 hour after a single oral dose, of 150 mg and maintained an average of 0. 28 mcg/ml for 12 hours following the administration.
4) Average urinary excretions of clindamycin 6 hours and 24 hours following a sin gle oral administration of 150 mg were 4. 96 mg (3. 2%) and 10. 9 mg (7. 3%) respectively.
5) The clindamycin concentration in bile attained the peak o f 7. 15 mcg/ml 4 hours after a single oral dose of 150 mg. Clindamycin was not detected 12 hours after administration.
6) Oral administration of clindamycin, 600 to 1, 200 mg per day, in 9 patients with surgical infections was evaluated effective in 8 and poor in 1.
Two of the 9 patients complained of uppe r abdominal pain during the clindamycin therapy, but this pain disappeared with concomitant administration of a digestive without discontinuing clindamycin.
Clindamycin, superior to lincomycin in antibacterial activity on staphylococci, is co nsidered an antibiotic very useful in treatment of infections due to resistant Staphylococcal strains.

View full abstract

Laboratory and surgical studies of clindam ycin, a new derivative of lincomycin, were conducted with the following results:
1. In an evalua tion of the in vitro antibacterial activity of clindamycin, the minimal inhibitory concentrations determined against 51 strains of Staphylococcus aureus isolated from the lesion of various surgical infections were 0. 9 mcg/ml or below in 47 strains, 3. 12 mcg/m1 in 1 and 100 mcg/ml or above in 3.
2. Wit h a single oral dose of 150 mg, the blood level reached the peak of 1. 19 mcg/m1 at 2 hour. In the case of a 300 mg also orally dosed, the peak level was 3. 57 mcg/ml at 1 hour.
3. Clindamycin was administered to 35 patients with surgical infections such a s furuncle, cellulitis, felon, carbuncle, acute suppurative mastitis, abscess, osteomyelitis, erysipelas, etc., and an excellent or good clinical response was observed in 29 (82. 9%) of them.
4. No side effects were noted except abdominal pain in I patient and slight digestive disturbance in 2 patients.

View full abstract

1) Antibacterial activity
Clindamycin s howed better antibacterial activity on Staphylococcus aureus than erythromycin and lincomycin, but it had no activity on Escherichia coli.
2) Absorption and excretion
After an oral do s e of 150 mg, clindamycin penetrated quickly into blood, attaining the peak (average 0. 87 mcg/ml) following one hour after administration. Urinary excretion, on the other hand, was low, the average 12?hour recovery being 3. 69 mg (2. 46%).
Milk transfer was late. The peak concentration, wh i c h was attained 3 hours after administration, was about 2/3 of the peak blood level. In contrast, the biliary concentration was ab out 5 times as high as the blood level.
3) Clinical effectiveness
Clindamy c in administered to 27 cases of surgical infections proved excellent in 4, good in 18, and poor in 5 in response (success rate 81. 5%). The only side effect observed was slight nausea in one patient.

View full abstract

Of the 19 strains of Staphylococcus aureus separa ted from the lesions of our out-patients, 58% were found resistant to penicillin, 31. 5% to tetracycline, 15. 8% to streptomycin and oleandomycin, and 10. 5% to kanamycin and chloramphenicol, while none was resistant to clindamycin.
Four of the 83 staphylococcal strains derived intradermally from s urgical wounds required 12 m cg/ml of lincomycin as MIC while their growth was inhibited by clindamycin with a concentration below 0. 8 mcg/ml.
Clindamycin proved effective in 13 of 16 out-patients and in each of 3 inpatients to whom it was administered. Only side effects observed of clindamycin were mild stomach ache in 2 patients.

View full abstract

It was examined that the- concentrations transferred into various organs or materials in obstetrical and gynecological field by oral administration of 300 mg of clindamycin.
1) The concentration into mother's serum was in the high est level at 1 hour after administration and revealed 3. 4 mcg/ml.
2) The transfe rences into the umbilical cord blood were, in contrast to the existing antibiotics, higher than those of mother's serum.
3) The transferences into am niotic fluid and mother's milk were in low level and the values were minimal.
4) The transferences into the fetus or embryonal organs, if even 9 weeks of pregnancy, were demonstrated. However, the transferences into the organs of fetus were at the maximum level in the kidney.

View full abstract

Clindamycin is a derivative of lincomycin, developed by Upjohn laboratory.
This drug was used in the obstetrical and gynecological fields.
The minimum inhibitory concentration was 0. 20 mcg/ml to Staphylococcus aureus.
The distribution of MIC was from 0. 39 to 3. 13 mcg/ml to Staphylococcus 209 P.
Blood concentration reached to the peak 1 hour after 150 mg oral admi nistration, and the peak appeared 1 hour after 300 mg oral administration.
The total urinary excretion in 24 hours was 21. 9 mg and corresponded to 14. 6%.
Transition into milk was satisfactory.
But concentration in umb ilical blood and amnion-water were low and detected only by 300 mg oral administration.
Transition in genital organs was measured and 3. 1∼5. 3 mcg/ml of blood concentration were obtained. The concentration was 0. 72∼1. 25 mcg/ml in cervix, and 0. 62∼1. 40 mcg/ml in tuba respectively.

View full abstract

1. The M. I. C. of clindamycin and lincomycin against 36 strains of Staph. aureus, including 21 strains resistant to penicillin G (7 resistant to erythromycin), ranged 0. 045-0. 09 mcg/ml and 0. 09-1. 56 mcg/ml respectively, with the exception of 3 strains which required more than 50 mcg/ml for inhibition by either clindamycin or lincomycin, thus showing superiority of clindamycin over lincomycin in antibiotic strength. The M. I. C. of clindamycin and lincomycin against 4 strains tested of Strep. faecalis was both 50 mcg/ml.
2. The clindamy c in blood level in two adult subjects given a single oral dose of 150 mg attained the peak in 1 to 2 hours after administration, which averaged 2. 6 mcg/ml, and maintained an effective level for considerably long time.
3. As for urinary excreti on, 15. 3% (average) of the dose was collected within 6 hours after a single 150 mg administration of oral clindamycin in 2 adult patients.
4. Milk transfer attained the peak 4 hours after a single 150 mg administration of oral clindamycin in 2 subjects. The peak concentration averaged 1. 3 mcg/ml.
5. Clindamycin was clinically effective in 13 (76. 5%) of 17 cases of pelvic infections, mastitis puer-, peralis, external genital infections, ureteral infections, etc.
6. No symptoms of side effects were observed in a ny patient treated with clindamycin. Hepatic function tests (Meulengracht, GOT, GPT, alkaliphosphatase), renal function tests (BUN, urinary protein, sediment), etc., conducted on 3 cases showed no abnormal changes.

View full abstract

From the laboratory and clinical studies on clindamycin, a new antibiotic, the following results were obtained.
1. The sensitivity of 30 strains, isolated from pathological materials in our clinic, to clindamycin was measured by the plate dilution method. Staphylococcus aureus strains were inhibited to grow at the rate of 69. 2% by the presence of 0. 20 mcg/ml or less. Clindamycin was found to have almost complete cross resistance with lincomycin. Gram negative bacilli were highly resistant to this antibiotic.
2. Single oral dose of 150 mg produced serum peak at 1 hour of an average level of 1. 6 mcg/ml in 3 adults.
3. Tissue concentration of clindamycin in tonsils were measured. An average tissue level of 0. 45 mcg/g at 1 hour after oral administration of 150 mg was obtained.
4. Clindamycin was clinically used to 36 cases of ear, nose and throat infections chiefly due to gram possitive cocci and it was effective in 72. 2% of them.

View full abstract

We have recently obtained the result described below through the laboratory and clinical studies on clindamycin.
1) The minimum inhibitory concentration in clindamycin was measured by agar plate dilution method. Clindamycin inhibited Staphylococcus aureus 40 strains with ≤0. 19∼≥100 mcg/ml (0. 19 mcg/ml: 22 strains). Clindamycin, however, could not inhibit Pseudomonas aeruginosa (30 stra ins) and Proteus vulgaris (3 strains) with 100 mcg/ml.
2) The level of blood concentration of clindamycin was determined by the average of 3 cases of adult. The maximal level reached 4. 6 mcg/ml after 2 hours in oral administration of 300 mg. And blood level still maintained 0. 25 mcg/ml in 12 hours after per os.
3) Urinary excretion concentration was determined by the a verage of 3 cases of adult. The urinary excretion rate after 300 mg was 15. 6% in 12 hours.
4) By oral administration or local application ( 10 mg/m1 solution) on 33 cases in otorhinolaryngologic field, clindamycin produced a good result of 85% (28 cases).

View full abstract

The present authors have carried out clinical application of clindamycin chiefly for treatment of otorhinolaryngological infections.
1. Antistaphylococcal activity of sera after administration of 150 mg (CLC) was analyzed by their effects on the growth-curve of 209 P strain automatically recorded by biophotometer. The results demonstrated that effective concentration in serum was maintained for 1-6 hours.
2. Twenty-four cases of the infections were treated with clindamycin to obtain the following results: excellent in 7 cases (29. 2%), good in 14 (58. 3%), poor in 7 (21. 2%). The success rate is thus 87. 5%.
3. No side effects, s u ch as hypersensitivity, eruptions and hearing disturbances were observed in any patient treated with clindamycin.

View full abstract

Clindamycin has been well tolerated by 32 patients with pyogenic infection of the eye and proved effective for 30 cases. The agent was ineffective against 1 case of acute dacryocystitis.
By laboratory test 7 out of 41 strains of pathogenic staphylococci showed re sistance to the clindamycin. The same strains showed resistance to erythromycin, lincomycin, suggesting the presence of cross-resistance mechanism.

View full abstract

Bacterial and clinical experiments for ophthalmic use of clindamycin (CLM) were performed and the results summarized as follows.
1) Minimum growth inh i bitory concentration of CLM was 2. 5∼5 mcgfml for Koch-Weeks bacillus, 2. 5 mcgiml for Morax-Axenfeld bacillus, 0. 005∼5 mcg/m1 for Pneumococcus, 0.005 mcg/ml for Corynebact. diphtheriae, 0. 5 mcgiml for Gonococcus, 0.05∼10 mcgiml for Streptococcus, 0.05∼0. 5 mcg/m1 for Staphylococcus and >100 mcg/ml for Pyocyaneus.
2) The distribution of sensitivity for 100 strains of Staph. aureus isolated in 1967 was in the range of ≤0. 1∼>100 mcg/ml, and majority of them (87%) were in ≤2. 5 mcg/ml.
3) Cross-resistance was recognized between CLM and LCM.
4) The concentration-in the blood by oral administration of 150 mg CLM in a single dose reached the highest after 1 hour and decreased gradually until 8 hours.
5) After oral administration of 100 mg/kg CLM to rabbi t, the concentration in the aqueous humor was recognized from 1 to 6 hours, and peak was reached after 2 hours. The tissue concentration at 2 hours was high in iris and ciliary bo d y, retina and chorioid, extraocular muscles, lid and conjunctiva.
6) After instil l ation of 1% CLM eye-drops the concentration in the aqueous humor of the rabbit eye, reached the highest after 2 hours, and the tissue concentration at 2 hours was high in cornea, conjunctiva, lid and extraocular muscles.
7) After subconjunctival injection of 5 mg/0. 5 ml CLM, the concentration in the aqueous humor of the rabbit eye reached the highest after 1/2 hour and decreased until 6 hours. The tissue concentration at 1/2 hour was high in conjunctiva, extraocular m uscles, cornea and sclera.
8) The oral application of CLM against eye patient revealed excellent e ffects on 2 cases of ulce rative blepharitis, 15 cases of hordeolum, each one case of acute chalazia, chronic dacryocystitis and acute tenonitis, 2 cases of infiltration of the cornea and each one case of orbital celluitis and post-operative infection. Preventive administration against post-operative infection was effective in all 20 cases.
9) Side effects: Some patients complained of nausea, abdominal pain, epigas tralgia and vertigo, but any other serious one was not noticed.

View full abstract