Clindamycin-2-phosphate, a newly developed injectable antibiotic, was bacteriologically evaluated in comparison with the parent compound, clindamycin.
Clindamycin-2-phosphate has a rather weak antibacterial activity. However, it is metabolized into clindamycin in vivo. And this parent compound shows strong activity against both gram-positive bacteria and gram-negative cocci. In vitro studies demonstrated that clindamycin-2-phosphate and clindamycin are affected by the pH of the medium used-the antibacterial activity becomes stronger as the medium is made more alkaline-while they are little affected by the size of the inoculum.
in mice with experimental infections, clindamycin-2-phosphate showed about the same therapeutical effect as clindamycin in contrast with the former's inferior in vitro activity as compared with the latter.

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[in Japanese]

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Ten adult patients with severe Bacteroides infections were treated with 0.9-1.8g/day of parenteral or oral clindamycin, and a child was treated with 0.3g/day orally. Remarkable responses and cures were obtained in all the patients, who had no underlying diseases and pure anaerobic infections; a case of sepsis, two cases of liver abscess, a case of subcutaneous abscess and a case of spinal epidural abscess. The other six patients who had ultimately fatal underlying diseases or mixed infections did not respond well to the combination of clindamycin and the other antibiotics therapy, althought bacteriological cures were obtained in all but two cases. Clindamycin was well tolerated and generally nontoxic, nevertheless it was administrated for long term (34-49 days). But transient development of transaminase was seen in a patient. The data suggested that clindamycin should be considered a first choice antibiotic for the treatment of an aerobic, especially, Bacteroides infections.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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Clindamycin-2-phosphate (7 (S)-chloro-7-deoxylincomycin-2-phosphate) is a new semi-synthetic antibiotic. It is recognized that the drug itself is inactive against bacteria in vitro but it is hydrolyzed rapidly to active clindamycin, drug intramuscular or intravenous administration.
Clindamycin-2-phosphate was administrated intravenously to seven patients with infections, except one intramuscularly, 300-600mg, every 8 or 12 hours a day, for 2-12 days.
Three patients (1 bacterial pneumonia, 1 chronic bronchitis and 1 urinary tract infection due to E. coli) recovered from their infection; one patient (bacterial infection in bronchiectasis) partially responded; and three patients (1 urinary tract infection due to E.coli, 1 pneumonia due to Mycoplasma pneumoniae and 1 patient with Mycoplasmal pneumonia and acute biliary tract infection) failed to respond to the drug.
No remarkable side effect was noted except pain at intramuscular injection site in one patient.

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Preclinical and clinical studies of clindamycin-2-phosphate developed as an injectable were conducted, and the following results were obtained:
1) Clindamycin-2-phosphate administered by the intravenous drip in a dose of 600mg over one hour showed a peak blood clindamycin level of 10.5mcg/ml at the end of administration. Though the blood level then decreased rapidly, it stayed at 0.7mcg/ml at 8 hours later.
2) The blood level of clindamycin following intramuscular injection of 300mg of clindamycin-2-phosphate reached a peak of 3.3mcg/ml at one hour later. The blood level at 6 hours after injection was 1.0mcg/ml.
3) Clindamycin-2-phosphate 300mg was given intramuscularly 2 to 4 times daily for 5-14 days in 4 cases of pneumonia. The drug proved effective in two cases of pneumonia due to Mycoplasma; fairly effective in another case of mixed infection caused by pneumococci, Hemophilus and N. meningitidis; and ineffective in the fourth case of infection due to Hemophilusp arainfluenzae.4) No such adverse reactions as hepatic disorder, renal disorder and colitis were noted following administration of clindamycin-2-phosphate.

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[in Japanese]

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[in Japanese]

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Blood levels of clindamycin-2-phosphate in dog at dosis of 10mg/kg body weight showed the maximum of 21μg/ml 30 seconds after one-shot i.v. administration. Continuous infusion of the antibiotic at the infusion speed of 150 and 300ml/hour/10kg b. w. with 6 mg/ml solution maintained blood levels of 30 and 170μg/ml respectively. It may be recommended clinically to use lower concentration than 6mg/ml to avoid cardiocirculatory disturbances.
Four cases of surgical mixed infections with gram-positive cocci, gram-negative bacilli and anaerobes were treated with clindamycin-2-phosphate at a daily dosis of 1,200mg intravenously and 2 of 4 cases revealed good clinical response. There was none of the haematological, hepatic, nephrotic, cardiocirculatory and allergic side effects.

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Twenty eight patients were treated with parenteral clindamycin-2-phosphate in the field of surgery, and good response was obtained in a series of superficial soft tissue infections, especially caused by staphylococci, with a daily dose of 300mg.
Serum level and urinary excretion were also investigated in four healthy male volunteers.

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Fundamental and clinical investigation with a new antibiotic, clindamycin-2-phoshate, were performed with the results which may lead to following conclustions.
1) Concentration in blood: The blood level of clindamycin-2-phosphate in healthy adults who were given 300mg by intramuscular injection reached a peak level of 4.3μg/ml one hour after injection. Even after 6 hours, clinically effective serum concentration of 0.5μg/ml was still demonstrable.
2) Concentration in tissues: Clindamycin-2-phosphate activity was demonstrable at the concentrations of 1.6-2.3μg/g in human palatine and mucous membrane of maxillary specimen one hour after the intramuscular injection of 300mg. Further the concentration was 2.9-5.4μg/ml.
3) Results of clinical treatment: When clindamycin-2-phosphate was injected intramuscularly in 30 cases of representative infections in the otorhinolaryngologic field, it was excellent in 12 cases, good in 12 cases, fair in 4 cases and poor in 2 cases. Excellent and good results were obtained in 24 cases, being the effectiveness 80 per cent.
4) Side effect: No side effect was shown with the intramuscular injection of clindamycin-2-phosphate. The comparative examination of hepatic function, electrolyte and auditory acuity before and after injection showed no significant disturbance.

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Some laboratory examinations were made with clindamycin-2-phosphate (CLDM-2-phos.). The drug was applied clinically to several otorhinolaryngological infections and the good results were obtained as follows.
1) Observing by biophotometer, the growth of Staphylococcus aureus FDA 209P was inhibited well by the serum (diluted 10-fold) 30 minutes, 1, 2, 4 hours after 300mg of CLDM-2-phos. were injected intramuscularly.
2) Serum concentration was determined by thin-layer method with Sarcina lutea ATCC 9341 as the test organism. The peak of serum level was obtained at 1 hour after a single intramuscular injection of 5mg/kg or 10mg/kg dosis of CLDM-2-phosphate. The peak of blood concentration was 5.4μg/ml, 5.6μg/ml respectively.
3) CLDM-2-phosphate concentration in tissues was estrimated one hour after intramuscular injection of CLDM-2-phosphate. The concentrations in blood and palatine tonsilla were 5.0μg/ml and 2.9μg/ml respectively after the intramuscular injection of 10mg/kg. The concentrations in blood and mucous membrane of maxillar sinusitis were 4.1μg/ml and 2.5μg/ml respectively after the intramuscular injection of 10mg/kg.
4) CLDM-2-phosphate was administered by intramuscular injection into 30 cases with various infections in otorhinolaryngological field. The clinical results were excellent in 22 cases (73.3%), effective in 3 cases (10.0%) and ineffective in 5 cases (16.7%). The effectiveness was 83.3%.
5) No side effects were observed in 30 cases.

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Bacterial and clinical experiments for ophthalmic use of clindamycin-2-phosphate (CLDM-2-P) were performed and the results were summarized as follows.
1. The distribution of sensitivity for 100 strains of Staphylococcus aureus isolated in 1975 was in the range of ≤0.19-≥100μg/ml, and majority of them (96.0%) were in ≤0.39μg/ml.
2. The serum concentration by intramuscular injection of 300mg and 600mg CLDM -2-P in a single dose respectively reached the peak level after 2 hours and decreased gradually until 12 hours in both of them.
3. Ocular penetrations were examined in rabbit eyes.
(1) After instillation of 1% CLDM-2-P solution, the aqueous level reached the highest after 1 hour and measurable after 6 hours.
(2) After subconjunctival injection of 5mg/0.5ml CLDM-2-P, the aqueous level reached the highest after 2 hours and decreased until 6 hours.
(3) After intramuscular injection of 100mg/kg, the aqueous concentration was recognized from 1 to 8 hours, and peak was reached after 1 hour.
Aqueous-serum ratio in 1 hour was 37.13%.
The ocular tissue concentrations at 2 hours showed relatively high levels in both of outer and inner parts of the eye.
4. The intramuscular injection of CLDM-2-P, 300-1800mg daily, against suppurative ocular infections revealed excellent effects on cases of external hordeolum, acute chalazion, lid abscess, or-bi tal phlegmone, corneal infiltration, corneal ulcer, and iridocyclitis purulenta.
5. Side effects: Two cases out of 22 cases complained of diarrhoea and bitter taste after injection, and able to be treated continuously by the drug. No abnormal findings in hepatic and renal tests were observed and no severe side effects like allergic reactions were recognized.

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Clindamycin-2-phosphate was studied to evaluate its possible use in ophthalmology.
1. Sensitivity of organisms isolated from human clinical materials: Of 44 staphylococcal strains in vitro studied 13 were highly sensitive to 0.1μg/ml and 28 were resistant to 100μg/ml or more of clindamycin-2-phosphate.
2. In experiments with rabbits, clindamycin-2-phosphate showed superior penetration into the ocular tissues after intravenous injection than after intramuscular injection.
3. Clindamycin-2-phosphate was administered intramuscularly at the dose of 300mg to 6 healthy volunteers. The blood concentrations of 6 cases averaged 3.2μg/ml after 1 hour, and 0.8μg/ml after 6 hours.
4. Fourteen patients with extraocular infection were treated with daily intramuscular administration of 300mg of clindamycin-2-phosphate. All of them improved by the treatment, and no side effect was observed.

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[in Japanese]

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1. MIC against 20 strains of staphylococcus isolated from skin infections was studied. MIC was ≤0.05μg/ml in 11 strains and >100μg/ml in 9 strains.
2. Clindamycin-2-phosphate was injected intramuscularly to rats at the dosis of 10mg/kg in solution of 10mg/ml. The serum and skin levels of this drug were determined at 0.5, 1, 2, 4 and 7 hours. Mean serum levels of 4 rats were 0.893, 0.578, 0.463, 0.268 and 0.167μg/ml respectively at 0.5, 1, 2, 4 and 7 hours. The corresponding skin levels were 0.500, 0.707, 0.431, 0.313 and 0.269μg/g.
3. Clindamycin-2-phosphate was used clinically in 7 patients of skin infection with the following result: excellent in 2 cases, fair in 3 cases and poor in 2 cases. Abdominal pain was complained in one case and loose stool in one case.

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Six patients with biliary tract infections who came to our hospital were administered 1.5g (potency) per day of amoxicillin, a synthetic penicillin for oral use, to examine its clinical effects. The results were as follows.
1) Out of six patients with biliary tract infections, amoxicillin proved to be effective in four patients, ineffective in one patient, and unknown in one patient.
2) Oral administration of amoxicillin gave the same success in treatment as injection of other synthetic penicillin preparations in mild cases with the exception of acute deterioration of chronic with subjective symptoms such as nausea and vomiting.
3) No noteworthy side effects were observed in any cases examined this time.

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Amoxicillin, a synthetic penicillin with a broad antibacterial spectrum, was administered in a daily dose of 1.0g (in potency) to 47 patients who came to the department of urology (6 patients in whom the antibiotic was used for the prevention of infections included). The results are summarized in the following.
1. The patients with urological infections who were treated with amoxicillin included 20 patients with acute cystitis, 1 with acute urethritis, 18 with chronic prostatitis, 1 with epididymitis, 1 with pyelonephritis and 6 patients in whom the antibiotic was used for the prevention of infections. Amoxicillin was remarkably effective in 27 patients (58.7%), effective in 7 patients (15.2%), but ineffective in 12 patients (26.1%), with the overall effectiveness of 73.9%. The therapy was withdrawn in one patient because of side effects.
2. A patient with acute cystitis showed eruption which was probably associated with allergic reaction to penicillin, and the administration was discontinued. Other side effects worth mentioning were not observed.

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