Renal elimination of ceftazidime during pregnancy.

OBJECTIVE: Our purpose was to study the pharmacokinetics of ceftazidime at different stages of pregnancy and in the nonpregnant state to determine whether glomerular filtration rate is altered and whether tubular secretions occurs. STUDY DESIGN: Twelve pregnant women with asymptomatic bacteruria were given a bolus dose of 400 mg of ceftazidime followed by a constant infusion for 4 hours. Inulin was infused simultaneously to determine glomerular filtration rate. Blood samples were drawn every 30 minutes. Urine was collected immediately after the bolus dose and then every hour. The same study procedure was then repeated twice: 2 weeks before the expected delivery and after termination of breast-feeding. RESULTS: At term clearance values were raised by 50% to 100% compared with the values found in the postpartum period. At all observation points a close correlation between inulin and ceftazidime clearance values were found. CONCLUSION: The results strongly indicate that ceftazidime is excreted exclusively by glomerular filtration with no tubular reabsorption. During pregnancy the excretion pattern is unaltered, but renal elimination is increased.

Intraocular levels of cefuroxime in inflamed rabbit eyes.

The pharmacokinetics of cefuroxime was studied in the inflamed rabbit eye employing subconjunctival, intravitreal and combined intravitreal-intravenous routes of administration to study the intraocular levels and the duration of minimum inhibitory concentrations (MIC) of the antibiotic in the vitreous and in the aqueous. A standard inoculum of viable S. aureus was injected into the vitreous of 36 pigmented rabbits to establish experimental endophthalmitis. A biological method was used for the antibiotic assay. Penetration of systemically and subconjunctivally administered-cefuroxime into the inflamed vitreous was poor. Intraocular inflammation increased the clearance of the intravitreally injected cefuroxime. A dose of 75 mg subconjunctivally produced levels in the aqueous far exceeding MIC for over six hours. Penetration of intravitreally injected cefuroxime into the aqueous was poor, inconsistent and short lasting. Following a single intravitreal injection of 1000 micrograms cefuroxime, levels exceeding the MIC for common ocular pathogens persisted in the vitreous for at least 24 hours but supplementation with intravenous cefuroxime neither increased the intraocular levels nor delayed the clearance of the intravitreally injected antibiotic.

Antibiotic treatment in Lyme borreliosis.

Before the etiology of Lyme borreliosis became known, its human manifestations were most often treated with penicillin. Treatment was mostly successful, in spite of the fact that lower doses were generally used, but the doses were given with shorter intervals. Lately, other antibiotics have been tried, more or less successfully, but there is still no consensus as to which--if any--antibiotic is superior to others, or if one manifestation of the infection is better treated than another with a particular antibiotic.

Intraocular levels of cefuroxime in uninflamed rabbit eyes.

Intraocular levels of cefuroxime following subconjunctival, intravitreal and combined intravitreal and intravenous administration were determined in uninflamed rabbit eyes. Intraocular levels of the antibiotic were assayed by a biological method. Penetration of cefuroxime into the vitreous following subconjunctival administration was poor. Subconjunctival administration produced higher levels of cefuroxime in the aqueous when compared to parenteral administration alone. Higher levels of cefuroxime were achieved both in the aqueous and in the vitreous after an intravitreal injection. Intravitreal injection of 100 and 1000 micrograms cefuroxime produced intravitreal levels close to the minimum inhibitory concentration (MIC) for most ocular pathogens up to 24 h after drug administration. Intravenous supplementation did neither enhance the intraocular levels nor did it delay the clearance of the intravitreally injected antibiotic. Mild histopathological changes were seen with equal frequency both in the control and the test eyes and are attributed to the sampling techniques. Electroretinography (ERG) showed no definite changes suggestive of retinal toxicity up to 55 days after intravitreal administration.

Role of aqueous and vitreous cultures in diagnosing infectious endophthalmitis in rabbits.

Staph.aureus endophthalmitis was induced in both eyes of 32 rabbits. Endophthalmitis developed in all the 64 eyes within 24-36 h. All vitreous cultures were positive while only 21 simultaneous aqueous cultures were positive. Thus, the importance of vitreous cultures in diagnosing bacterial endophthalmitis is emphasised.

Incidence of endophthalmitis in Sweden.

A retrospective review of all suspected and proven cases of endophthalmitis (EO) during a period of 18 months in Sweden is presented. This period covered the time of transition in the surgical technique at a large number of clinics. Sixty-two cases of EO were reported out of which 52 were post-operative. A total incidence of post-operative endopthalmitis (POE) was found to be 0.33%. The incidence of culture proven POE was however only 0.06%. No cultures or only conjunctival cultures had been taken in 32 (61.5%). S. epidermidis and S. aureus comprised the majority of isolates. No case of fungal EO was reported. The number of posttraumatic EO was low.

Visual outcome of endophthalmitis in Sweden.

A retrospective study of 62 cases of clinically diagnosed endophthalmitis (EO) reported from 24 clinics in Sweden was carried out. Both culture negative and positive cases were included. The function of the eye was lost in 34% of all cases, while vision better than 0.1 was preserved in 41% cases. Staph. epidermidis positive and culture negative cases were associated with better visual results. The majority of eyes with cultures positive for Staph. aureus were lost or became blind. Intravitreal injection of antibiotics and vitrectomy was generally reserved for more severe cases often involving a delay in their institution. A combination of topical and systemic steroids gave better results than no steroids or only topical steroid administration.

Oral trimethoprim as follow-up treatment of meningitis caused by Listeria monocytogenes.

Successful treatment of meningitis and septicemia caused by Listeria monocytogenes with intravenous trimethoprim-sulfamethoxazole has previously been reported. This case report of a 13-year-old boy with meningitis caused by Listeria monocytogenes documents complete cure with 6 days of intravenously administered trimethoprim-sulfamethoxazole followed by orally administered trimethoprim as monotherapy.

Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women.

The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy. Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during and after pregnancy. For both drugs most pharmacokinetic parameters were altered in pregnancy. The area under the plasma concentration-time curve (AUC) following intravenous administration was smaller for both drugs during as compared to after pregnancy (mean change 39% for cephradine and 31% for cefazolin). Half-lives of both drugs were significantly shorter during compared with after pregnancy (mean change 26% for cephradine and 35% for cefazolin). Consequently, total body clearance was increased during pregnancy. A significant negative correlation between length of gestation and total clearance per kg bodyweight was seen for cephradine. The bioavailability of oral cephradine did not differ significantly during compared with after pregnancy. It is concluded that the dosage of both cefazolin and cephradine should be increased when treating infections in pregnant women in order to obtain the same antibacterial effect as when treating non-pregnant women.

Effect of imipenem/cilastatin on the colonic microflora.

The effect of imipenem/cilastatin on the colonic microflora was investigated in 10 patients receiving the drug for six to 11 days. Fecal specimens were cultured quantitatively for aerobic and anaerobic microorganisms before, during, and after therapy. Imipenem/cilastatin treatment was associated with minor changes in the colonic flora. A small decrease in the numbers of enterobacteria, enterococci, anaerobic cocci, and organisms of the Bacteroides fragilis group was observed. After treatment was discontinued, the microflora returned to normal in all patients, and no new colonization with imipenem-resistant bacteria was seen. No patient had Clostridium difficile or its cytotoxin in feces. No adverse gastrointestinal reactions were registered.

Impact of imipenem/cilastatin therapy on faecal flora.

To evaluate the effects of parenteral imipenem/cilastatin therapy upon human faecal microflora, stool specimens obtained from ten patients before, during and after therapy were cultured quantitatively for aerobic and anaerobic microorganisms. The patients received 500 mg imipenem combined with 500 mg cilastatin every 6 h for 6-11 days. The antimicrobial therapy was associated with a small decrease in the numbers of enterobacteria, anaerobic cocci and bacteroides during treatment but afterward the microflora normalized in all patients. None of the patients was colonized with new imipenem-resistant bacteria, had Clostridium difficile or cytotoxin in the stools, or developed diarrhoea.

Pharmacokinetics of cefuroxime in pregnancy.

Most pharmacokinetic studies of antibodies in pregnancy have been carried out at the time of abortion or delivery. Whether such data represent pregnancy as such is not known. The present study compares the pharmacokinetic properties of cefuroxime in seven women during pregnancy, at delivery, and after delivery. After intravenous administration of 750 mg of cefuroxime, levels of the drug in plasma and urine were measured during a period of 8 hours. Levels of cefuroxime in cord plasma and amniotic fluid were registered, as were levels of plasma from the neonates at 6 and 12 hours. Plasma levels were significantly lower during pregnancy than afterward, drug half-life was significantly shorter, and clearance and recovery in urine were significantly higher. Differences, although less consistent, were observed in certain parameters at delivery, as compared to earlier in pregnancy, thus indicating that pharmacokinetic data obtained at delivery may not be typical of pregnancy as such. Passage of cefuroxime across the placenta was well demonstrable in all cases.

Persistance of ampicillin in the intrauterine content following single and multiple doses to pregnant women.

Cord plasma, and amniotic fluid (AF), as well as maternal plasma from women who had been given ampicillin in single or multiple doses prior to delivery were assayed for levels of the antibiotic. If medication had been discontinued two days prior to delivery or less, ampicillin could still be demonstrated in AF, where it remained demonstrable longer than in cord plasma. Ampicillin, when given during pregnancy, crosses the placenta, enters the fetal circulation, and is excreted by the fetal kidneys into the AF. The results of the present study indicate that as medication is continued, the level of ampicillin in AF rises through continuous renal excretion by the fetus. Once medication is discontinued, ampicillin is slowly cleared from the AF mainly through absorption from AF to fetal circulation and further passage to maternal circulation.

A protocol design for studying alterations of pharmacokinetic parameters due to pregnancy.

A study protocol is described by means of which useful and pertinent information on possible alterations of pharmacokinetic parameters due to pregnancy can be investigated. Whenever any drug is prescribed to a pregnant woman for medical reasons, pharmacokinetic data for that drug can be obtained by determination of drug levels in urine, plasma or serum, or other possible tissues. The same data should later be obtained for an identical dose of the same drug given to the same woman after pregnancy. By comparing pharmacokinetic parameters in the same woman during pregnancy and after--when she serves as her own nonpregnant control--clinically and statistically significant differences may be discovered with a comparatively small patient material. As in each case the drug that is studied is prescribed for medical reasons, this protocol involves no undue risks for the pregnant woman or the fetus.

Pharmacokinetics of antibiotics in pregnancy and labour.

Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be representative for pregnancy as such. Marked changes in most organ systems, particularly in renal function, but in composition and amounts of body fluids as well, make it likely that several pharmacokinetic parameters change, possibly gradually as pregnancy progresses. Accumulated data for several beta-lactam antibiotics, and also for aminoglycosides indicate that antibiotics eliminated mainly by renal excretion will produce lower levels in serum or plasma in pregnant women than in other individuals. Also, the half-life of certain antibiotics in serum is shorter during pregnancy. Transplacental passage occurs for all antibiotics according to the physicochemical properties of the drug. Bolus injections to a pregnant woman are more efficient than continuous infusion in producing high levels of antibiotic in fetal serum and amniotic fluid. Fetal tissue levels are higher following multiple doses than after a single dose. Lower serum levels of antibiotics in pregnant women than in other individuals following the same dosage will be unsatisfactory as micr-organisms are less likely to be affected.

Plasma and urine levels produced by an oral dose of ampicillin 0.5 G administered to women taking oral contraceptives.

Earlier studies have shown that ampicillin produces 50% lower-and therefore very likely less adequate-plasma levels in pregnant than in nonpregnant women. The present investigation compares levels of ampicillin in plasma and urine produced by a single oral dose administered to 10 healthy women taking oral contraceptives on the 21st and on the 28th day of the menstruation cycle. Plasma levels of ampicillin were lower on the 21st day than on the 28th, i.e. a difference in the same direction as between pregnant and nonpregnant women although the difference was not significant. Contrary to what was found for pregnant women the dose of ampicillin to women taking oral contraceptives does not have to be doubled in order to compensate for lower plasma levels.

PIP: Because in pregnant women administration of ampicillin produces plasma levels of about 50% those reached in these same women when they are not pregnant and because oral contraceptive use causes a pregnancy-like condition, a study was conducted to investigate the effect of oral contraceptive use on plasma and urine levels of ampicillin. A single oral dose of .5 gm ampicillin was administered to 10 healthy oral contraceptive users on the 21st and 28th days of their cycles (8 used levonogestrel .25 mg, ethinyl estradiol .05 mg; 1 used levonogestrel .5 mg, ethinyl estradiol .05 mg; and 1 used lynestrenol 2.5 mg, ethinyl estradiol .05 mg). It was found that plasma levels were lower on the 21st day at 1, 2, 3, and 8 hours than on the 28th day with a significant dfference occurring only at 1 hour. Mean values for peak level, ACU, CIR 0-8 hours, and recovery in urine were also lower on the 21st day, but not significantly. Although this trend is the same as that seen in pregnant versus not pregnant women, the plasma levels of ampicillin on the 21st day compared well with levels found in nonpregnant women. Therefore, no further investigation is warranted.