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Background: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy., Methods: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment., Results: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar., Conclusions: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate., (© 2024. The Author(s).)

Clinical trial of cefotiam was made in children and the following results were obtained. 1. Pharmacodynamic studies of the drug in CSF of experimental staphylococcal meningitis in rabbits showed a CSF/serum ratio of T 1/2 of 3.52, which was relatively high, but a percentage of CSF/serum ratio of AUC of only 3.42% up to 3 hours, suggesting a low efficiency of passage of the drug into CSF. 2. Blood concentrations of the drug were determined in children after an intravenous bolus injection of 20 mg/kg and were 46 mcg/ml (15 min.) and 26 mcg/ml (30 min.), T 1/2 being 40.8 min., Urinary recovery rate was 91.3% up to 4 hours in one patient and 61.9% up to 6 hours in another, respectively. 3. Thirteen patients with the following 14 episodes of infections were treated with cefotiam; urinary tract infection (5 cases), pneumonia (5), empyema (1), tonsillitis (1) and suspected sepsis (2). An overall efficacy rate was 100%, i. e., excellent in 12, good in 2 and no failure. No adverse reactions were clinically discernible and only laboratory abnormalities were transient or slight elevations of transaminase levels in 2 patients. 4. Based on the above results, it was concluded that cefotiam is a potent new antibiotic in the treatment of bacterial infections. Spectrum and antibacterial activity of the drug suggest that the drug particularly indicated for pneumonia.

A clinical study on cefotiam (CTM) was performed in the field of pediatric infection, and the following results were obtained: The number of cases studied were six including 2 cases of U.T.I., 1 case of vaginitis and vulvitis, 1 cervical lymphadenitis, 1 absence of thigh and coxitis. Clinical responses to CTM were excellent in 3 cases, good in 1 cases but there was 1 exception who dropped out because of concurrent use of other antibiotics. As for bacteriological responses, CTM eliminated the pathogens E. coli and P. mirabilis from U.T.I., Staph. epidermidis and P. morganii, from vaginitis and vulvitis, H influenzae and Str. pneumoniae from cervical lymphadenitis and Staph. aureus from abscess of thigh. No side effect was observed except 1 case who showed an elevation of GOT, GPT and LDH. It is uncertain, however, wether this abnormality was resulted from the use of CTM or not, because the other antibiotics were used also.

Studies on the antibacterial activity, absorption and excretion and also clinical investigation in the field of pediatrics have been carried out with cefotiam (SCE-963, CTM), a new cephalosporin antibiotic. 1) The MICs of CTM against the following clinical isolates were measured and compared with those of CEZ: S. aureus (81 strains), E. coli (27) and K. pneumoniae (27), with CTM being inferior by 1 tube in S. aureus, being superior by 2 to 3 tubes in E. coli and by about 2 - 3 tubes in K. pneumoniae. 2) Absorption and excretion. After intravenous one shot injection at dose levels of 10 mg/kg and 20 mg/kg, the peak in the serum concentration was shown in the 15-minute value with 18.1 and 36.6 mcg/ml for 10 mg/kg and 20 mg/kg, respectively. The half-life in ;the serum was 1.14 and 0.61 hours, respectively. In the case of 1-hour intravenous drip infusion at a dose level of 10 mg/kg, it was 14.3 mcg/ml, with 0.98-hour half-life in the serum. The recovery rates from the urine within 0 to 6 hours were 50.6% and 66.2% in the case of intravenous one shot injection at dose levels of 10 mg/kg and 20 mg/kg, respectively, with 71.1% in the case of the 1-hour intravenous drip infusion. 3) Two to 3 hours after intravenous one shot injection of CTM in H. influenzae-meningitis every 4 hours at a dose level of 62.5 mg/kg at one time, the cerebrospinal fluid concentration of CTM was only 2.12 to 10.0 mcg/ml, and this fact suggests that CTM is a useful cephalosporin for treating purulent meningitis. 4) CTM was administered in 19 clinical cases, with the results being: excellent in 4 out of 4 cases of bronchitis; excellent in 5 and good in 1 out of 6 cases of pneumonia; excellent in 3 cases of pyelitis; good in purulent parotitis, purulent meningitis and bacterial pericarditis; and excellent in peritonsillar abscess, purulent osteomyelitis and staphylococcal scalded skin syndrome (S.S.S.S.). No side effects have been observed in all cases. As for abnormal laboratory findings, 3 cases of eosinophilia were seen.

A new synthetic cephalosporin, cefotiam (CTM) was studied from the basic and clinical aspects, and the following results were obtained: 1. Bacteriological study: The bacterial activities of CTM against the clinical isolates of S. aureus, S. pyogenes, E. coli, Klebsiella sp. and Proteus sp. were compared with those of CEZ, CER, ABPC and GM. (1) As for S. aureus and S. pyogenes, the antibacterial actions of the conventional cephalosporins were slightly more potent than those of CTM. (2) However, CTM had the antibacterial actions which were most potent Proteus sp. among the above 4 antibiotics and more potent against E. coli and Klebsiella sp. than the above 2 conventional cephalosporins. 2. Pharmacokinetic study: The peak serum levels of CTM were comparatively low with 19.30 +/- 1.66 mcg/ml 30 minutes after a bolus injection of 20 mg/kg and 25.85 +/- 4.32 mcg/ml just after a drip infusion of 20 mg/kg. The half-life of the serum levels was 0.98 hrs. and 0.87 hrs., respectively. The 4 hours urinary excretions in six patients ranged from 38.6 to 64.9%, showing a slightly wide variance. 3. Clinical study: The clinical response was good in 23 out of total 25 cases, i.e. 14 cases with respiratory tract infection, 7 with urinary tract infection and 4 with skin and soft tissue infection. The response rate was 92%. Also, neither side effects nor abnormal laboratory findings was observed.

The fundamental and clinical studies on cefotiam (CTM) were performed in the field of pediatrics, and the following results were obtained: 1. The peak MIC's of CTM against Gram negative rods such as E. coli, Klebsiella, Salmonella, Proteus were 1.56 mcg/ml. The MIC distribution against S. aureus was almost equal to the conventional cephalosporin antibiotics. The MICs against P. pseudomonas and Serratia were over 400 mcg/ml. 2. The mean serum levels of CTM after bolus intravenous injection of 25 mg/kg were 59.9 mcg/ml after 15 min., 30.0 mcg/ml after 30 min., 15.6 mcg/ml after 1 hour. 3. Administration of CTM to 6 pediatric patients produced the clinical responses which were good in all 6 cases and the bacterial effects of eradication in 3 cases and superinfection in the 2 cases in the 5 cases from whom the organism were isolated. No side effect was observed. From the above results, it is considered that a bolus injection of CTM 25 mg/kg t.i.d. to q.i.d. is a safe and useful treatment for pediatric cases.

The influence on bowel flora of CTM was studied in 5 children who were taking normal diet. 1) In the cases following no diarrhea, administration of CTM caused no significant changes in bowel flora. In the cases following diarrhea, administration of CTM caused a fall in coliform, BEP group, Lactobacillus and Peptostreptococcus. However, after the administration was discontinued, the reduced bowel flora was returned to the normal range within a few days. 2) No overgrowth of bowel flora by Pseudomonas, Clostridium difficile or Candida was observed. 3) One strain of nontoxigenic Clostridium difficile was observed in the case of following no diarrhea. 4) As for the side effects, diarrhea was observed in 2 cases. BEP group: Nonspore making anaerobic Gram positive rods of Bifidobacterium, Eubacterium, Propionibacterium.

240 and 183 strains of non-PPNG and PPNG isolated in 1981 were studied for their susceptibility to ceftriaxone and cefotaxime respectively. All the strains were susceptible to 0.016 microgram/ml of either antibiotic. PPNG from males were less susceptible to cefotaxime than non-PPNG or PPNG from females. PPNG isolated in 1979 were less susceptible to gentamicin than non-PPNG. The relatively high MIC values of cotrimoxazole may account for the high treatment failure rate encountered with the drug.

Cefotiam (CTM) were clinically applied to 6 cases and the following results were obtained: 1. The patients were aged 1 year in 5 cases and 7 years in 1 case. They comprised three cases of acute tonsillitis and 1 case each of phlegmon, bronchopneumonia and cervical abscess. CTM was administered in a daily dose of 50-115 mg/kg t.i.d. by an 1-hour intravenous drip infusion for 4 to 8 days. 2. The causative bacteria were S. aureus in 3 cases and H. parainfluenzae, K. pneumoniae and unknown pathogen in each 1 case. The organisms were eradicated in all cases except for only 1 case of S. aureus. 3. Overall responses were good in 4 cases and fair in 2 cases. 4. As for the abnormal laboratory findings, slight increase of GOT and GPT was observed in 1 case. Any other side effects were not observed.

The basic and clinical studies of cefotiam (CTM) in pediatric infections were carried out, and the following results were obtained: 1. The antibacterial activity of CTM against S. aureus was equal or slightly less than that of cefazolin (CEZ). Those of CTM against E. coli and K. pneumoniae were eight times more active than those of CEZ. 2. CTM 20 mg/kg was administered wither by 30 minutes or 1 hour intravenous drip infusion. The peak serum levels were obtained at the end of each drip infusion, with the mean peak levels being 44.8 and 41.4 mcg/ml respectively. The serum levels at 1.5 and 2 hours after drip infusion were 2.8 and 2.2 mcg/ml respectively, and at 3.5 and 4 hours after drip and 4 hours after drip infusion were 0.3 and 0.7 mcg/ml respectively. The half lives were 0.62 and 1.15 hours, respectively. The mean urinary excretion over 6 hours were 52.8% in ;the 30 minutes drip infusion group and 42.6% in the 1 hour drip infusion group. 3. Clinical efficacy was evaluated in sixteen cases suffering from tonsillitis (4 cases), pneumonia (4), bronchitis (2), cervical lymphadenitis (2), purulent meningitis (2), suppurative arthritis (1) and suspected sepsis (1). Good and excellent responses were obtained in 15 of 16 cases (93.8%). Bacteriological response in the form of eradication was noted in 4 of 6 cases. Side effect observed was rash in 1 case, and laboratory abnormalities were elevation of BUN in 1 case and elevation of GPT in 2 cases.

We measured the activity of rosoxacin, fosfomycin, cefotiam, and spectinomycin against 51 isolates of beta-lactamase producing Neisseria gonorrhoeae, all of which were susceptible to each drug at sufficient concentrations. The development of strains of penicillinase producing N gonorrhoeae (PPNG) which are resistant to spectinomycin can therefore be avoided, as there are alternative drugs.

Susceptibilities to cefotiam of 103 strains of 27 bacterial species were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zone by the single-disc method, under the experimental condition established by Kanazawa. The experiments demonstrated significant correlation between MIC by the dilution method and diameter of inhibition zone in each of conventional assay of the over-night (about 16 hours) incubation, delayed assay (about 24 hours incubation), and rapid assay (about 3--4 or 5--6 hours incubation), thus confirming applicability of the single disc assay for cefotiam. Analysis of the data obtained by using cefotiam disc containing 30 micrograms revealed the primary regression equation to be: D (diameter, mm) = 25.6--10.1 log MIC (micrograms/ml) in conventional assay, D = 32.8--13.2 log MIC (micrograms/ml) in delayed assay, D = 17.2--5.8 log MIC (micrograms/ml) in 3--4 hours rapid assay and D = 21.0--7.8 log MIC (micrograms/ml) in 5--6 hours rapid assay, respectively. The range of variations in MICs estimated from the diameter of inhibition zone by the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution assays, as reference for the experimental errors which may be involved in the estimation of MIC of cefotiam by the single-disc assay.

The bactericidal activity of rifampin plus other antibiotics was examined with in vitro checkerboard dilutions against 15 strains of staphylococci, with time-kill studies, and with determinations of serum bactericidal activities (SBAs) in volunteers. In vitro synergism was found consistently only in inhibitory assays with rifampin plus minocycline. Time-kill studies with rifampin plus methicillin revealed enhanced killing at concentrations close to the MBC but reduced combined activity at higher concentrations. SBAs with rifampin, oxacillin, and the two drugs in combination were studied in three treatment regimens (regimen A: 2 g of oxacillin and 300 mg of rifampin; regimen B: 1 g of oxacillin and 450 mg of rifampin; and regimen C: 3 g of oxacillin and 450 mg of rifampin). The SBA against methicillin-sensitive Staphylococcus aureus was significantly lower with the two drugs in combination than with oxacillin alone in regimen A but not in regimen B. In vitro synergy with rifampin plus other antibiotics was not frequent. At high concentrations, the bactericidal activity of oxacillin was reduced by rifampin, but killing activity may be enhanced at low concentrations of oxacillin.

Cefotiam (CTM) is a new synthetic cephem antibiotic developed in Japan. The results of the fundamental and clinical studies are as follows. 1. CTM showed antibacterial activity, in terms of MIC, as strong as those of cephalothin (CET) and cefazolin (CEZ) for Gram-positive cocci, and several times superior to for Gram-negative bacilli. 2. CTM serum levels approximately reached the peaks on completion of 60 minutes intravenous drip infusion of 1 g of this preparation dissolved in 5% glucose solution of 250 ml; the mean value was 65.00 micrograms/ml. Then the levels dropped rather quickly up to 180 minutes after the start of drip infusion. After that, the levels dropped gradually up to 360 minutes. 3. As for the passage of CTM in the oral tissues, satisfactory passage was observed in both maxillomandibular marrow and gingiva, which adequately exceeded MICs of the clinically isolated strains of oral infections. 4. This preparation was administered 1 g of 2 g daily by intravenous drip infusion in 18 cases of moderate or more serious infections in the field of oral surgery; the clinical efficacy rate obtained was 94.4%. 5. No manifestations of side effect were observed clinically. As for laboratory findings, 1 case of large increases in GOT and GTP (a hepatitis B antigen positive patient) and 2 cases of slight increase in GTP were observed. On the basis of these results of the fundamental and clinical studies, it was concluded that CTM is an excellent antibiotic for the treatment of oral infections.

The studies on cefotiam (CTM) administered by intravenous drip infusion in pediatric field made the following results: 1. The serum levels after administration of cefotiam 25 mg/kg, 63 mg/kg by intravenous was maintained high until 2 hours after and kept to be able to measure after 5 hours, and the half life was 0.9-1.7 hours. 2. The drug transferred actively about 1/5 of serum level into the intrathoracic pus. The excretion rate in urine was about 80% of the drug administered. 3. The clinical effective rate after the administration of CTM 50-70 mg/kg for 4 to 29 days was 95% in 21 patients with different five diseases. 4. No side effect and abnormality in laboratory findings were observed.

Cefotiam is a new semisynthetic cephalosporin antibiotic. The treatment with this drug was carried out in 12 cases of pediatric infection. The clinical response was observed in 92% of the cases. Cefotiam was found to be active against a variety of Gram-positive and Gram-negative bacteria. Neither marked side effects nor laboratory abnormalities were found with this treatment.

Unlabelled: The therapeutic effects of cefotiam (CTM) in the pediatric field were studied, and the following results were obtained: 1. Absorption and excretion: After 30 minutes intravenous drip infusion of 250 mg (14.7 mg/kg) of CTM to a 5-year old child weighing 17 kg, the serum levels and urinary excretion were measured. The serum levels were 47.8 mcg/ml at 30 minutes after administration, 23.9 mcg/ml after 1 hour, 12.5 mcg/ml after 1 hour and 30 minutes, 5.2 mcg/ml after 2 hours and 30 minutes, 0.3 mcg/ml after 6 hours and 30 minutes. Excretion rate in the urine was 48.8% at 6 hours after administration. 2., Clinical Results: CTM was administered at a daily dose of 35 to 91 mg/kg b.i.d. to q.i.d. by intravenous or intravenous drip injection for 2 to 6.5 days to six patients i.e. two with bronchopneumonia, one with acute bronchitis, one with acute enteritis, one with impetigo and atopic dermatitis one with acute tonsillitis and acute cervical lymphadenitis. The responses were excellent in 2 cases and good in 4 cases. The response rate was 100%. No side effect was observed.

In order to demonstrate the distribution of an antibiotic to normal breast tissues and its penetration into the axillary wound exudate, 1 g of a new cephem antibiotic, cefotiam (CTM), was infused intravenously over 1 hour in 14 patients with breast cancer before and after mastectomy. CTM concentrations were assayed by the cylinder-plate method, using Proteus mirabilis ATCC 21100 as the test organism. Overall CTM levels in the normal breast tissues ranged from 3.6 to 27.7 micrograms/g, and 5.2 micrograms/g of CTM still remained 170 minutes after administration. No significant differences were found in CTM levels of 3 parts of the breast tissue from the same patient. Serum CTM levels rapidly declined after the end of infusion of CTM. Concentrations of CTM in axillary wound exudate after mastectomy ranged from 5.2 to 13.6 micrograms/ml at 3 hours after administration and were almost undetectable at 24 hours. It is concluded that CTM levels in breast tissues were almost the same as those in other tissues.

The objective of this study was to evaluate the concentration in the bronchial secretions of a new injectable cephalosporin, cefotiam, which is characterized by an excellent antibacterial activity, stability against beta-lactamases and interesting pharmacokinetic properties. 30 patients suffering from acute exacerbation of a chronic bronchitis or bronchiectasis with expectoration, received either 1 g i. v. of cefotiam in a single dose or four doses of 1 g each over a period of 3 days. The bronchial secretion samples were obtained by fibroscopy, 1, 2, or 4 h after the last dose, in order to evaluate the kinetics of the bronchial concentration of cefotiam. Blood samples were taken simultaneously in order to establish a possible correlation between the bronchial and serum levels of the drug. The results of the study show a rapid and significant transfer of the drug through the bronchoalveolar capillaries, elevated bronchial concentrations starting from the 2nd h, reaching 10 micrograms/ml (or more) in certain cases, slow elimination with bronchial concentrations persisting at high levels for up to 4 h and a ratio between bronchial and serum concentrations of 25-60% at the 2nd h and more than 100% at the 3rd and 4th h. These results confirm the excellent diffusion of cefotiam, especially in the respiratory tract, allowing bronchial levels largely superior to the minimum inhibitory concentrations required to kill the bacteria usually responsible for lower respiratory tract infections.

Clinical investigation of combination use of cefotiam (CTM), aminoglycoside, or (and) penicillin against complicated infections with hematopoietic disorders was performed, and the results were as follows. Fifty-one patients were administered CTM in combination with aminoglycoside or (and) penicillin. The clinical response was excellent 19.6%, good 27.4%, fair 21.6%, and poor 31.4% showing efficacy rate of 47.1%. The combined therapy of CTM and aminoglycoside was clinical effective in 70% of 10 patients with complicated sepsis. Therefore, combination use of CTM and aminoglycoside is considered to be the first choice for the treatment of complicated sepsis with hematopoietic disorders. The clinical effectiveness of CTM was not influenced by the number of mature neutrophil at the first phase of CTM treatment, but was influenced at the end phase of CTM treatment. Gram-negative bacilli were dominantly isolated from the patients. Pseudomonas sp. was isolated from 70% of the patients with sepsis. No remarkable side effects were observed in this investigation.

Repeated subcultivation of Neisseria gonorrhoeae in the presence of subinhibitory concentrations of antibiotic has turned out as a reliable model to predict the low potential for development of resistance with respect to the beta-lactam antibiotic penicillin. Before large-scale introduction of the new cephalosporins we exposed 5 N. gonorrhoeae strains of different susceptibility to penicillin repeatedly to subinhibitory concentrations of cefotiam, ceftizoxime, rifampicin and penicillin G incorporated into chocolate agar. each time the most resistant representatives of a strain were propagated, on the whole 25 times. While resistance to rifampicin increased readily (all strains became relatively resistant, MIC = 4 micrograms/ml), the same was not true of the cephalosporins. Although their susceptibility decreased, too, no strain acquired partial or even total resistance (final MIC less than or equal to 0.128 with cefotiam and ceftizoxime). The cephalosporins thus rather parallelled penicillin G which hardly induced any increase of resistance. Thus, a quick loss of clinical efficacy need not be feared after large-scale introduction of the new cephalosporins into the therapy of gonorrhea.

Cefmenoxime is a new syn-methoxyimino cephalosporin antibiotic derived from cefotiam, which has been proved to be a very effective and useful antibiotic for the treatment of respiratory infections. This bacteriological and pharmacokinetic study was therefore performed in order to evaluate the potency of cefmenoxime in the treatment of respiratory infections. The minimum inhibitory concentrations of cefmenoxime against 179 isolates of respiratory pathogens (Streptococcus pneumoniae 53, Haemophilus influenzae 64, Klebsiella pneumoniae 43, Escherichia coli 9, Enterobacter spp. 10) were less than 0.20 micrograms/ml, and 43 (73%) of 60 Pseudomonas aeruginosa were inhibited by 12.5 micrograms/ml. In vitro antibacterial activity of cefmenoxime was superior to 18 other antibiotics, including cefotiam and cefotaxime tested in this study. Pharmacokinetic studies on tissue distribution in rats, serum levels and urinary excretion in 3 healthy volunteers, and penetration into bronchial secretes of 9 patients with respiratory infections, revealed that cefmenoxime has a higher penetration into the lung and bronchial secretes compared with cefotiam and cefotaxime. In 1 patient with chronic bronchiolitis, the concentration of cefmenoxime in the intra-bronchial secrete reached 12.5 micrograms/ml. From these results, it is concluded that cefmenoxime is a highly potent and useful antibiotic, and may be more effective in the treatment of respiratory infections than many other cephalosporins, including cefazolin, cefotiam and cefotaxime.

The MICs of cefotiam and cefazolin against K. pneumoniae DT-S were unaffected by the inoculum size and were 0.1 and 1.56 micrograms/ml, respectively. Bactericidal and bacteriolytic activities of the cephalosporins were more potent in bacterial concentrations of 10(7) colony-forming units (CFU)/ml than in concentrations of 10(8) CFU/ml. Both activities of cefotiam were more markedly influenced by bacterial concentrations than those of cefazolin. Therapeutic activity of cefotiam was about 9 approximately 15 times as potent as that of cefazolin in experimental pneumonia caused by K. pneumoniae DT-S in mice, and this finding was in accordance with the ratio of in vitro antibacterial activities of the two cephalosporins as judged by the MICs or the bactericidal and bacteriolytic activities in bacterial suspension of 10(7) CFU/ml. The range of concentrations of cefotiam which induced cell filamentation in vitro, was wider than that of cefazolin. This difference, however, was not reflected on the therapeutic activities of the two cephalosporins in the model infection. In the pneumonic lungs, definite therapeutic doses of both cephalosporins (80 mg of cefotiam per kg and 640 mg of cefazolin per kg) produced mainly bacteriolysis of the challenge organisms.

We have administered cefotiam intravenously to 23 pediatric patients. The daily dose was 13-210 mg/kg. The clinical responses were excellent and good in 20 cases. Excluding 1 case with infectious mononucleosis, the efficacy rate of 90.9% (20/22 cases) was achieved As for side effect, diarrhea and eosinophilia were observed one each in 2 cases. In 2 cases, half lives were 24 and 53 minutes, urinary recovery rates were 88.3 and 91% over 6 hours.

Our investigation of cefotiam in pediatric infection produced the following results: 1. Cefotiam was administered intravenously by one shot or drip infusion in 20 patients with infectious diseases. These diseases consisted of 13 pneumonia, 3 upper respiratory tract infections, 3 pyelonephritis, 2 other urinary tract infections and one purulent meningitis. Cefotiam was effective in all cases. 2. Transient elevation in serum GOT, GPT, Al-P and LDH was observed in 3 cases. But other side effect was not noted in any cases.

During recent decades there has been a controversial discussion if comparable plasma level profiles which are rather constant or those which show a high peak are more efficient for the cure of gonorrhoea. So far, investigations in this field were not based on the Grasso apparatus. Although the findings with cefotiam and ceftizoxime do not allow to formulate a general hypothesis without any restriction, it can be stated that on the basis of an identical area under the antibiotic level time curve, 'peak concentration' profiles are more favourable.

The effect of subinhibitory antibiotic concentrations on the phagocytosis of Staphylococcus aureus was studied by pretreating 3H-thymidine labelled bacteria with one-third the minimal inhibitory concentration of clindamycin, doxycyclin, cefotiam, vancomycin, piperacillin and penicillin G, respectively. Pretreatment with clindamycin and doxycyclin resulted in enhanced uptake of the bacteria by polymorphonuclear leukocytes compared to the untreated control. The augmented phagocytosis was still observed at 1/32 the MIC of clindamycin and 1/64 the MIC of doxycyclin, and when the serum was diluted to a concentration of 1%. Pretreatment of the bacteria with penicillin, cefotiam, piperacillin and vancomycin had no effect on phagocytosis. Inhibitors of bacterial protein synthesis induce alterations of Staphylococcus aureus leading to increased phagocytosis, whereas antibiotics acting on cell wall synthesis are without effect.

A subacute (5-week) subcutaneous toxicity study of cefotiam (CTM) was carried out using 9 three-week old Beagle puppies. The puppies were assigned to one of three groups, each containing three. Puppies in group I (control) were given physiological saline; puppies in group II and III were given 300 mg/kg/day of CTM and cefazolin (CEZ), respectively. No behavioral abnormalities were seen in puppies in each group. The changes, considered to be drug-related, were histopathological changes at the sites of injection, which consisted inflammatory cellular infiltration, hemorrhage and hyperplasia of fibroblast in connective tissue of skin and skeletal muscle. In terms of severity, CTM was rather more irritating than CEZ. Except the histopathological changes described above, there observed no abnormalities which were considered to be related to CTM.

Cefotiam (CTM) was evaluated for its safety and efficacy in children. Twenty-six patients were treated with 40 to 200 mg/kg per day of CTM by intravenous administrations. The diagnosis of the patients were acute pharyngitis (2), acute bronchitis (1), pneumonia (4), empyema (2), urinary tract infection (2), typhoid fever (1), acute enterocolitis (2), partially-treated purulent meningitis (1), and suspected septicemia in neuroblastoma (1); and the remaining ten patients were considered to have nonbacterial infections. The pathogens recovered were Streptococcus pyogenes (1), Streptococcus pneumoniae (1), Staphylococcus aureus (4), Haemophilus influenzae (4), Escherichia coli (1), enteropathogenic Escherichia coli (1), Salmonella typhi (1), and Campylobacter jejuni (1). All but two patients of bacterial infections were cured after the CTM therapy, and the rate of efficacy was 87.5%. Diarrhea (3), urticaria (1), transient elevation of GOT and GPT (1), and transient eosinophilia (3) were found to be associated with the CTM therapy. However, no severe adverse reactions were encountered. Half life of the serum CTM level was 0.93 +/- 0.13 hours, and excretion into the urine was rapid. CSF concentration obtained 1 hour after an intravenous injection of 21 mg/kg of CTM in a case with inflamed meninges was 1.5 mcg/ml, and the CSF/serum ratio was 9.0%. From these data, CTM appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections.

Four new beta-lactam antimicrobials, ceftriaxone, cefotiam, cefonicid, and mecillinam, were evaluated in vitro against 72 beta-lactamase-negative and 26 beta-lactamase-positive isolates of Neisseria gonorrhoeae. Ceftriaxone was the most active of the antimicrobials tested. It inhibited all isolates, regardless of beta-lactamase activity, at a concentration of less than or equal to 0.015 microgram/ml. Cefotiam and cefonicid were also active against both groups but not as active as ceftriaxone. Both groups of N gonorrhoeae showed a high degree of resistance against mecillinam.

Antibacterial activity of cefotiam associated with gentamicin, tobramycin, netilmicin, or amikacin against Enterobacteriaceae strains either moderately susceptible (MIC = 4 to 32 micrograms/ml, 14 strains) or resistant (MIC = 64 to 512 micrograms/ml, 22 strains) to cefotiam was studied using the checkerboard method. High rates of synergic associations (FIC index less than or equal to 0.5) were found, with variations according to the aminoglycoside: 65% for tobramycin and netilmicin, 76% for amikacin, and 81% for gentamicin. Activity of cefotiam is increased by the synergic effect of these associations: of the 36 strains tested, 83, 78 and 76% became susceptible to cefotiam (MIC less than or equal to 4 micrograms/ml) associated with tobramycin, netilmicin or gentamicin, and amikacin respectively.

Cefotiam, one of the new cephem antibiotics, was used in 14 cases with pediatric infections: (10 cases with respiratory tract infections, 2 with urinary tract infections, each 1 with purulent meningitis + sepsis and acute appendicitis). The patients were aged between 15 days and 9 years old. The drug was, a rule, given at a daily dose of 50 mg/kg to 100 mg/kg q.i.d. by bolus intravenous injection. The duration of treatment was between 3 and 38 days. The treatment produced the following clinical responses: Out of the 10 cases, good response in 7 with respiratory tract infections, fair in 1 and poor in the remaining 2. The responses in urinary tract infections were excellent in 1 and good in the other case. An apparently clear response was obtained in 1 case with purulent meningitis + sepsis due to K. pneumoniae. Also, an excellent response was seen in 1 case with acute appendicitis. The response rate including fair response was 85.7%. The suspected pathogens isolated from 5 cases (S. aureus: 1. strain, H. influenzae: 1, K. pneumoniae 2, E. coli: 1) were eliminated after CTM administration. Good clinical responses were also obtained in these cases. No side effect was observed. Mild elevation of GOT and GPT was noted during the treatment in 1 case. It is unclear, however, if CTM was associated with this side effect or not. P. aeruginosa, Serratia appeared after superinfection in 1 case.

The in vitro activity of Cefotiam (Spizef) was tested using the agar diffusion test method according to DIN 58940 and compared with the antibacterial activity of 12 other routinely tested antibacterial chemotherapeutics. A total of 3000 strains from patients' specimens from the University Hospital of the Free University of Berlin and the Municipal Wenckebach Hospital, West Berlin, was tested. Cefotiam proved effective against strains of Staphylococcus aureus in 99,4%, Escherichia coli in 99,7%, Klebsiella species in 97,8%, Enterobacter species in 90,3%, Proteus mirabilis in 98,7%, indolpositive Proteus species in 91,7%, Citrobacter in 92,6%, and beta-hemolytic Streptococci in 99,3% of all strains tested. There were only few sensitive strains of Enterococci and of Pseudomonas aeruginosa.

Susceptibility to cefotiam of 494 bacterial strains was studied by MIC determination using an agar dilution assay. Activity of cefotiam was also compared with that of six other beta-lactams (ampicillin, mezlocillin, ticarcillin, cefalotin, cefotaxime, and moxalactam) using an agar diffusion method. Cefotiam showed a wide antibacterial spectrum including more than 70% of Enterobacteriaceae (except Serratia), beta-lactamase-producing and non-beta-lactamase-producing Haemophilus influenzae, non-enterococcus streptococci, and penicillinase-producing and non-penicillinase-producing staphylococci susceptible to methicillin. Conversely, cefotiam was inactive against Pseudomonas aeruginosa, Acinetobacter anitratum, Streptococcus faecalis, and methicillin-resistant Staphylococcus aureus.