A pharmacokinetic and clinical evaluation of ceftazidime in neonates and premature infants

Ryochi Fujii, Shintaro Hashira, Osamu Arimasu, Kozo Fujita, Ko ichi Murono, Hiroshi Sakata, Hitoshi Kakehashi, Toshiaki Oka, Masato Kaeriyama, Hajime Yoshioka, Shizuo Maruyama, Nobutaka Sanae, Fumie Inyaku, Yoshitake Sato, Satoshi Iwata, Hiroyuki Shiro, Yutaka Kusumoto, Tadao Oikawa, Mitsuru Osano, Keisuke SunakawaSusumu Nakazawa, Hajime Sato, Hidejiro Chikaoka, Kenji Niino, Yoshikiyo Toyonaga, Hironori Nakamura, Morimasa Sugita, Ken ichi Kawamura, Kiwamu Seo, Makoto Hori, Naoichi Iwai, Motohiro Shibata, Fumiko Mizoguchi, Haruhi Nakamura, Michihiro Katayama, Yoichi Taneda, Kazuyo Inokuma, Tadafumi Nishimura, Toshio Takashima, Kazuo Tabuki, Tsunekazu Haruta, Kan etsu Ohkura, Shigekazu Kuroki, Hatsumi Yamamoto, Mieko Yoshioka, Yutaka Kobayashi, Takashi Motohiro, Kōichi Tanaka, Tatsuhiko Koga, Yasushi Shimada, Shobun Tomita, Yasutaka Sakata, Tamotsu Fujimoto, Naoki Kuda, Koji Ishimoto, Kaoru Tominaga, Fumio Yamashita, Nobuhiko Takajo, Nobuo Hashimoto, Takuji Fujisawa, Shohei Kinoshita, Mitsuo Nakano, Shoichi Imai, Kiyotaka Nagayama, Yushiro Yamashita, Nobuo Tanaka, Suguru Takeishi, Yutaka Ishikawa, Koji Matsumoto, Hisaaki Araki, Yoshimi Tanaka, Takeshi Yuasa, Takeo Hashimoto, Teiji Akagi, Yasunao Kuroiwa, Noboru Sato, Hisaaki Kabatake, Kimiko Hara, Toshihiro Nishimi, Kozo Sakaguchi, Fujiko Hirose, Yoshiyuki Kimura, Miwako Tsunosue, Seiichi Fukuda, Hirofumi Nakajima, Hiroshi Matsuo, Masafumi Aramaki, Junko Kajiyama, Kyoko Shibao, Mizuho Horikawa, Yuji Yamashita, Jiro Yura, Yasuhiro Kamiya, Nobuatsu Tsuruga, Takashi Hashimoto, Hiroshi Narita, Yoshimi Akamo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Ceftazidime (CAZ) was evaluated for its pharmacokinetics and clinical usefulness in neonates and premature infants. The results obtained were summarized below. 1. Following intravenous injection of CAZ 10 or 20 mg/kg to neonates and premature infants, dose response was observed in serum concentrations ranging from 5.1 to 21.9 µg/ml at 6 hours after the injection. 2. The serum half-life tended to be longer in premature infants than in neonates; the half-life being longer for an infant with lower day-age. 3. Urinary recovery rates during the first 6 hours after single administrations of 10 mg/kg of CAZ tended to be higher in neonates than in premature infants, and higher rates were observed in older infants. However, no noticeable difference was observed after the administration of CAZ 20 mg/kg. 4. Clinical efficacy was evaluated in 99 neonates and 55 premature infants (156 infections), daily doses ranging from 21.1 to 246.4 mg/kg. 5. Out of 105 cases of common infections, mainly 44 cases with causative organisms identified (including 17 of sepsis, 7 of pneumonia, 4 of purulent meningitis, 11 of urinary tract infections) were examined for the clinical efficacy. The efficacy of CAZ was excellent in 21, good in 18, fair in 1 and poor in 4, with the efficacy rate of 88.6%. In the remaining 61 cases, i.e., 37 with causative organisms unknown and 24 with signs of intrauterine infections, the efficacy rate was 95.1%. Other than these cases, additional 51 cases were given CAZ solely for prophylaxis of infections, and the results were found satisfactory. On the whole, clinical efficacy rate of CAZ was 94.9% in 156 cases. 6. Out of the 44 cases examined for bacteriological responses, 38 were evaluated as ‘eradicated’, 3 ‘persisted’ and 3 ‘unknown’ with eradication rate of 92.1%. Replacement of organisms (superinfection) was observed in 3 cases. 7. Out of 179 cases in which adverse effects were assessable, adverse effects were observed in a total of 4 cases (2.2%), i.e., 3 cases of diarrhea (1.7%) and 1 case of rash (0.6%), and abnormal laboratory findings were observed in a total of 14 cases (7.8%), i.e., increase in eosinophiles count in 8 (4.5%), elevation of GOT in 3 (1.7%), increase in platelet, elevation of GOT·GPT, and elevation of GOT·GPT·BUN in 1 case each (0.6%). None of them were severe and they were transient. Elevations of bilirubin and cases of positive PIVKA II associated with CAZ were not observed. From the above results, the desired dosage of CAZ to neonates and premature infants should be in the unit dose of 20 mg/kg, 2 to 3 times daily to those with ages between 0 and 3 days, and 3 to 4 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion, with the maximum daily dose of 150 mg/kg, depending on symptoms.

Original languageEnglish
Pages (from-to)2048-2067
Number of pages20
Journalthe japanese journal of antibiotics
Volume39
Issue number8
DOIs
Publication statusPublished - 1986 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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