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Background: Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed., Methods: We searched Global Health, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Medline databases from inception to May 2015 for studies published on botulism or botulinum antitoxin use during pregnancy and the postpartum period, as well as the Centers for Disease Control and Prevention National Botulism Surveillance database. Our search identified 4517 citations., Results: Sixteen cases of botulism during pregnancy (11 in the third trimester) and 1 case during the postpartum period were identified. Ten cases were associated with confirmed or likely foodborne exposure; 2 cases were attributed to wound contamination related to heroin use, and the source of 5 cases was unknown. Eleven women with botulism had progressive neurologic deterioration and respiratory failure, requiring intensive care unit admission. Four women had adverse outcomes, including 2 deaths and 2 women who remained in a persistent vegetative state. No neonatal losses or cases of congenital botulism were reported. Among the 12 cases that reported neonatal data, 6 neonates were born preterm. No adverse maternal or neonatal events were identified as associated with botulinum antitoxin therapy among 11 patients who received it., Conclusions: Our review of 17 cases of botulism in pregnant/postpartum women found that more than half required ventilator support, 2 women died, and 6 infants were born prematurely. A high level of clinical suspicion is key for early diagnosis and treatment of botulism. Care of pregnant women or new mothers with botulism can include preparation for possible intubation., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Fanconi anaemia is a rare inherited disease characterized by congenital abnormalities, progressive bone marrow failure and predisposition to malignancy. Successful pregnancies in transplanted patients have been reported. In this paper we will describe the pregnancy of a patient with Fanconi anaemia without transplantation., Case Presentation: A 34-year-old nulliparous woman with Fanconi anaemia was referred to our institution. Pregnancy was complicated by progressive pancytopenia and two severe infections. C-section was performed at 36 weeks. Both infant and mother are well., Conclusion: Successful pregnancy in a Fanconi anaemia patient with bone marrow failure is possible. The mode of delivery in patients with bone marrow failure should be determined by obstetric indications. The case highlights the safe outcome of the pregnancy with strict clinical and laboratory control by a multidisciplinary team.

Objective: To perform culture and sensitivity for pathogens causing puerperal and postoperative wound sepsis and determine the frequency of Methicillin Resistant Staphylococcus aureus (MRSA) in such infections., Study Design: Observational study., Place and Duration of Study: Obstetrics and Gynaecology Ward, Jinnah Postgraduate Medical Centre, Karachi, from December 2008 to May 2010., Methodology: All patients presenting with puerperal sepsis or postoperative wound infection were enrolled. Pus was collected for culture and sensitivity using standard technique. Two samples were taken from each patient; one before starting the treatment and one at the end of treatment. Ames transport medium was used. Empirical treatment with triple regimen (Ampicillin, Metronidazole and Gentamicin) was started immediately to cover Gram positive as well as negative bacteria in addition to anaerobic infection. After receiving the sensitivity report, antimicrobial agent were changed accordingly. Samples from ward and theater staff and environment were also taken to look for possible mode of transmission. Data was recorded on a proforma. Discrete variables are expressed as percentages., Results: Staphylococcus aureus was the most frequent organism isolated in 34.6% cases. Methicillin sensitive Staphylococcus aureus was seen in 20% cases and methicillin resistant Staphylococcus aureus was seen in 14.6%. Out of these 14.6% MRSA, (17) 77% was associated with puerperal sepsis and rest (5) 23% was associated with postoperative wound infection. It showed best sensitivity to vancomycin., Conclusion: Staphylococcus aureus and E. coli were common causative agent of postoperative infections and puerperal sepsis.

Sepsis accounts for approximately 10% of all maternal deaths. Pregnant women are susceptible to certain infections because of alterations in their cell-mediated immunity. Obstetric sepsis requires early broad-spectrum antibiotic therapy and may necessitate surgical intervention. Group A streptococcal infection may produce necrotizing fasciitis and toxic shock. Pyelonephritis remains a common cause of sepsis during pregnancy, and associated acute respiratory distress syndrome occurs more commonly than in the nonpregnant population. Severe pneumonitis caused by influenza virus and varicella zoster infection may occur. Malaria may be more severe in the pregnant woman, and carries significant risk to both mother and fetus., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To assess associations between maternal mortality and severe morbidity and human immunodeficiency virus (HIV) infection, uptake of antiretroviral therapy, obstetric infections, and nonobstetric infections in a rural Malawian district, where the estimated HIV prevalence is 21%., Methods: We studied the incidence and outcomes of maternal peripartum infections between September 2007 and September 2009 at the district hospital. We used a facility-based prospective cohort study design, including all cases of severe maternal peripartum infection up to 42 days postpartum, and recorded maternal and pregnancy-related characteristics. We assessed the association between mortality and covariates (including nonobstetric infection, HIV prevalence, and uptake of antiretroviral therapy) using univariable and multivariable logistic regression models., Results: In total, 140 infections occurred: 79 (56%) obstetric and 53 (38%) nonobstetric (eight unknown). Half of the women were HIV-positive. Multivariable analysis showed that nonobstetric infection was the most important explanatory variable for mortality (adjusted odds ratio [OR] 4.23, 95% confidence interval [CI] 1.53-11.73). HIV-positive women not on antiretroviral therapy were at higher risk of mortality (adjusted OR 3.02, 95% CI 1.06-8.60) but there was no significant mortality increase among those on treatment (adjusted OR 0.51, 95% CI 0.10-2.71). The most common infections were puerperal sepsis (obstetric, case fatality rate 7%) and pneumonia (nonobstetric, case fatality rate 41%)., Conclusion: Untreated HIV infection and nonobstetric infections are independently associated with maternal mortality. Prompt treatment of HIV and nonobstetric infections in pregnant women must be prioritized to reduce maternal mortality., Level of Evidence: II.

Objectives: Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum., Methods: The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC(0-12)) was >or=10th percentile NFV AUC(0-12) in non-pregnant historical controls (18.5 microg h/mL)., Results: Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (C(max)), 12-h post-dose concentration (C(12)) and AUC(0-12) were significantly lower during the third trimester compared to postpartum (P

Objective: Paper describes risks of gynaecological inflamations and their treatment for the successful course of pregnancy., Design: Review., Setting: Czech Teratology Information Service, 3. LF UK, Praha., Subject and Methods: The article refers the most common types of vaginal inflamation and gives recommendation for the appropriate treatment that is safe for embryo or fetus according to advice of Teratology Information Service., Conclusion: Vaginal inflamation during pregnancy represents risks of abortion, miscarriage or prematurity. For the treatment, we have to take in consideration the age of pregnancy and we should use the drugs, that are safe during this period. It is necessary always to compare risks resulting from disorder and from drugs used.

We examined the efficacy of doripenem (DRPM), a carbapenem antimicrobial agent, against infectious diseases in gynecological and associated fields, as well as its safety. The following results were obtained: 1) The subjects were 20 patients with infection in the absence of pregnancy and 4 patients with pregnancy/puerperal infection. Intravenous drip of DRPM at 0.25 g x 2/day was performed for 3 to 8 days. The total doses ranged from 1.5 to 4.0 g. 2) Concerning its clinical efficacy, a complete response was achieved in 4 (16.7%) of the 24 patients, and a partial response in 18 (75.0%). The response rate was 91.7% (22/24). In 6 patients who did not respond to the previous agent, the response rate was 100% (6/6). 3) Concerning its clinical efficacy with respect to clinically isolated bacteria, a complete response was achieved in 3 (10.0%) of the 30 strains, and a partial response in 26 (86.7%). Bacteria disappeared in 29 (96.7%) of the 30 strains. 4) There were no side effects nor abnormalities in the laboratory data related to this agent. These results suggest the usefulness of DRPM in the treatment of gynecological infectious diseases.

Background: Optimal antiretroviral exposure during pregnancy is critical for prevention of mother-to-child HIV transmission and for maternal health. Pregnancy can alter antiretroviral pharmacokinetics. Our objective was to describe lopinavir/ritonavir (LPV/r) pharmacokinetics during pregnancy., Methods: We performed intensive steady-state 12-h pharmacokinetic profiles of lopinavir and ritonavir (three capsules: LPV 400 mg/r 100 mg) at 30-36 weeks gestation and 6-12 weeks postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured LPV and ritonavir by reverse-phase high-performance liquid chromatography. Target LPV area under concentration versus time curve (AUC) was > or = 52 microg h/ml, the estimated 10th percentile LPV AUC in non-pregnant historical controls (mean AUC = 83 microg h/ml)., Results: Seventeen women completed antepartum evaluations; average gestational age was 35 weeks. Geometric mean antepartum LPV AUC was 44.4 microg h/ml [90% confidence interval (CI), 38.7-50.9] and 12-h post-dose concentration (C12h) was 1.6 microg/ml (90% CI, 1.1-2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was 65.2 microg h/ml (90% CI, 49.7-85.4) and C12h was 4.6 microg/ml (90% CI, 3.7-5.7). The geometric mean ratio of antepartum/postpartum LPV AUC was 0.72 (90% CI, 0.54-0.96). Fourteen of 17 (82%) pregnant and three of 12 (25%) postpartum women did not meet our target LPV AUC. The ratio of cord blood/maternal LPV concentration in ten paired detectable samples was 0.2 +/- 0.13., Conclusions: LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls. Small amounts of lopinavir cross the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated.

We reported 22 cases with tuberculosis in pregnancy and puerperium, who were treated in our hospital from 1993 to 2001. Nine out of 22 cases were foreign women and the onset of tuberculosis was not clear and the diagnosis tended to be delayed in most cases. In the reports from industrial countries, most of those patients are foreign bone and the delay in diagnosis is common because symptoms are apt to be mixed up those for pregnancy and puerperium. In 10 of 22 cases, extrapulmonary lesions were noted. Most of our cases were treated with INH, RFP and EB, and in some severer cases PZA was added. WHO and BTS recommend standard therapy with PZA but ATS recommends INH, RFP and EB without PZA. Generally SM is contraindicated because of adverse effect of hearing loss for all pregnant periods, and the data for PZA and other second line drugs are insufficient. Our cases and their neonates showed normal course and no malformation nor congenital tuberculosis. 2 cases could not keep adherence for drugs and 2 babies got active tuberculosis. Precaution for infection is one of most important problem to deal with cases with tuberculosis during pregnancy and postpartum in the hospital. If she is still infectious on delivery, we should consider prevention for transmission and manage her in isolated manner. CDC recommends not to treat for latent tuberculosis during pregnancy because of high frequency of hepatic damage due to INH. It is the best way to check and treat latent tuberculosis before gestation if she is at high risk with tuberculosis.

Systemic fungal infections are rare. In pregnancy, treatment is problematic because of the risk of possible teratogenic effects of the antifungal drugs. We present the case of a 32 year-old woman who presented during pregnancy with a two-month history of painless subcutaneous nodules. Excision biopsy of one lesion showed dematiaceous fungal elements. Anti-fungal treatment was deferred and the pregnancy proceeded uneventfully. The remaining nodules were excised at the time of caesarean section delivery. Three weeks into the puerperium, she developed generalised seizures and investigations indicated systemic fungal infection with positive cultures for Aureobasidium spp which responded to appropriate antifungal therapy of flucytosine and itraconazole.

An investigation was carried out to determine the therapeutic effect of panipenem/betamipron (PAPM/BP), a injectable carbapenem antimicrobial agent, on infections in pregnant women during perinatal period. Of the 41 patients enrolled in the study, 34 were subjected to the analysis, with 1 exemption because of protocol violations (regimen), 3 because of uncertain evidence symptoms of infection, and 3 because of failure to undergo laboratory tests. PAPM/BP was administered by intravenous drip infusion at doses of 0.5 g twice or three times a day daily for periods of 3 to 14 days. The efficacy rate according to the evaluation of the Drug Efficacy Evaluation Committee and the attending physicians was 79.4% (27/34), with 49 of the 61 clinical isolates (80.3%) being eradicated. Safety was evaluated as "safe" in 39 of the 41 assessable patients (94.1%). Mild headache and nausea were experienced by 1 patient (2.4%) as adverse drug reactions, but the symptoms disappeared after the completion of treatment. Slight elevations of GOT, GPT and LDH in laboratory tests were observed in 1 patient (2.4%), but these values returned to normal after the completion of treatment. These results suggested that PAPM/BP may be a useful drug in the treatment of bacterial infections during the perinatal period. To firmly establish its safety, however, further clinical and pharmacokinetic studies are needed in larger populations.

Bacterial vaginosis being the most frequent vaginal infection is the leading cause of genital fluor. The author reviews the latest developments regarding the etiology, diagnostics and therapy of disease. Per os metronidazol and intravaginal clindamycin play the main role in treatment. The most often occurring complications of bacterial vaginosis are premature rupture of membrane and premature labour, postpartum endometritis, pelvic inflammatory disease and gynecological postoperative infections.

Pharmacokinetic and clinical studies of flomoxef (FMOX) in perinatal period were carried out and the following results were obtained. 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid were determined subsequently to intravenous injection (4 cases) and intravenous drip infusion method (20 cases) of 1 g FMOX. Maternal serum levels were similar to those of healthy adults, and peak levels of umbilical cord sera and amniotic fluids were 12.0 micrograms/ml and 12.05 micrograms/ml, respectively, using intravenous drip infusion. The levels in amniotic fluids were higher than those in umbilical cord sera at 2 hours after treatment in either administration method. Parameters T 1/2 (beta) and AUC were 1.05 hours and 74.1 micrograms.hr/ml, respectively. 2. In the treatment of 4 cases with perinatal infection and in prophylaxis cases, clinical efficacies of FMOX were all good with 1 g twice daily treatment using intravenous drip infusion. No side effects nor abnormal laboratory test values due to the drug were observed in any cases. These results indicate that single intravenous drip infusion of FMOX 1-2 g twice daily is effective for the treatment and the prophylaxis of perinatal infections.

Pharmacokinetic, bacteriological and clinical studies on flomoxef (FMOX) in the perinatal period were carried out with the following summary of the results. Antibacterial effects of FMOX on the growth of methicillin-resistant Staphylococcus aureus (MRSA, MIC 400 micrograms/ml), methicillin-sensitive S. aureus (MSSA, MIC 0.78 microgram/ml), Escherichia coli (MIC 3.13 micrograms/ml and MIC 0.20 microgram/ml) in amniotic fluid were determined and it was found that the activity of FMOX was enhanced in the amniotic fluid. FMOX rapidly penetrated into tissues and sera of pregnant women upon intravenous injection and its maternal serum concentrations reached their peak levels shortly after administration. Placental penetration of FMOX to the fetus was good and, after single intravenous injection of 1 g, the concentrations of FMOX in the umbilical cord serum and amniotic fluid exceeded MICs against major causative organisms of perinatal infections. These results indicate that single intravenous injection of FMOX 1 g twice a day is effective for the treatment and prophylaxis of perinatal infections. Injection of FMOX for the treatment of 14 cases of puerperal infections showed excellent clinical effectiveness with 100% clinical effect and 81.8% bacteriological response. No side-effect was observed in any case. All of these results suggested clinical usefulness of FMOX in the perinatal period.

We conducted clinical efficacy and safety tests of flomoxef (FMOX, 6315-S) in the perinatal infections and obtained the following results. 1. A total of 25 patients was treated: 16 patients with intrauterine infections, 2 patients with pelvioperitonitis, 4 patients with urinary tract infections and 3 patients with other infections. FMOX was injected at a daily dose of 2-4 g for 3-15 days (6-60 g for total dose) by intravenous drip infusion, intravenous injection or their combination. 2. The clinical efficacy rate was 96.0% of 25 patients: excellent in 4 cases (16.0%), good in 20 cases (80.0%) and poor in 1 case (4.0%). Bacteriological effects obtained were: eradicated in 14/16 cases (87.5%) replaced in 3 cases. 3. There were no subjective or objective side effects, nor were any abnormal laboratory test values attributable to the drug. From these findings, we consider that FMOX treatment appears to obtain good clinical and bacteriological responses and in safe in perinatal period infections.

Clinical efficacies of flomoxef (FMOX), which is a newly developed oxacephem antibiotic, were evaluated in 14 cases of obstetric and gynecologic infections during the perinatal period. The results were excellent in 6 cases (42.9%) and good in 8 cases (57.1%). No side effects nor abnormal clinical laboratory test results were observed in mothers or neonates. Thus, FMOX appears to be a useful antibiotic for perinatal infections.

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period were carried out. The results are summarized as follows. 1. The concentration of FMOX in umbilical cord serum was about 10 micrograms/ml in about 30 minutes after 1 g one shot intravenous injection. Amniotic fluid concentration was 7 micrograms/ml in 41 minutes after administration. By 1 hour intravenous drip infusion, FMOX concentration in umbilical cord serum was about 5 micrograms/ml in 2-3 hours after administration. Amniotic fluid concentration of about 20 micrograms/ml was found in 1 case. 2. FMOX 1-2 g x 2-3/day was given by intravenous drip infusion to 7 cases of perinatal infection for 4-26 days. Clinical efficacies were evaluated a good for all cases. Neither side effect nor abnormal laboratory test value was observed. Consequently, FMOX was considered to be highly effective and safe for its clinical use in perinatal period infections.

The placental passage and the the therapeutic efficacy of flomoxef (FMOX, 6315-S) were studied in patients in the perinatal period. A summary of the obtained results is as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid obtained upon one-shot intravenous injections to 12 patients were compared with those obtained upon 1 hour drip infusions to 9 patients. It was found that the former means of administration gave higher concentrations that the latter. 2. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid at 1 to 6 hours after administration through either method were all higher than MIC80's of recognized bacteria. 3. Clinical efficacies were evaluated in 10 patients with puerperal intrauterine infection, 7 patients with endometritis, 2 patients with pyelonephritis and 1 patient each with endo-cervicitis, amniotic fluid infection, mastitis and perineal wound infection. Clinical efficacies were excellent in 5 patients (21.7%), good in 17 patients (73.9%) and poor in 1 patient (4.4%), thus the overall efficacy rate was 95.7%. 4. Eradication of causative bacteria were obtained in all 8 cases tested, hence the eradication rate was 100%. 5. Mild diarrhea in 1 patient was the only side effect observed. No abnormal clinical laboratory test results were found in any patients.

In a population of 1011 puerperal women, the significance of rectovaginal colonization by group B streptococci during pregnancy with respect to infective puerperal morbidity was analyzed. Patients who were found to be carriers during pregnancy (121) were randomly divided into two groups: women who received ampicillin during delivery (500 mg i.v./6 h) and patients without chemoprophylaxis. Compared with the non-carriers, the carrier patients without prophylaxis had a significant increase in the mild puerperal infective morbidity, when defined as the proportion of women with an index fever greater than or equal to 10 (10.6% vs. 25%). However, the increased incidence among the carrier women of premature rupture of the membranes and of other possible morbidity factors made it impossible to identify the role of group B streptococci. Mild puerperal infective morbidity in the carrier women who received prophylaxis was lower than in those without prophylaxis and very similar to that of non-carrier women. It is concluded that the use of chemoprophylaxis to prevent neonatal sepsis would probably be followed by a reduction in infectious puerperal morbidity.

The clinical efficacy and the safety of imipenem/cilastatin sodium (IPM/CS) in perinatal infections were studied. The results are summarized below. 1. Clinical efficacy was evaluated in 12 patients with intrauterine infections (endometritis), 3 patients with amniotic fluid infections, 2 patients with puerperal fever and 3 patients with other infections. The drug was administered by intravenous drip infusion at a 0.5g to 1.0g dose as IPM and the total doses during an entire course of treatment were 1.5g to 15g. 2. Clinical efficacies were excellent in 4 (20%) and good in 16 patients (80%) and the efficacy rate was 100%. Ten patients had not improved upon treatments with other previous antibiotics. 3. Infective bacteria were eradicated in 4, decreased in 1, and replaced in 6 patients. 4. No side effects or abnormal clinical laboratory test values were observed in any patient.

Fundamental and clinical studies on latamoxef (LMOX) in the perinatal period were carried out, and following results were obtained. Concentration of LMOX was showed high peak levels in maternal serum, umbilical serum and amniotic fluid. LMOX seemed to be a very transferable compound to human tissues. LMOX was administered to 28 cases of various perinatal infections. Clinical responses were excellent in 13 cases, good in 15 cases and poor in none. And 140 cases of prophylactic use in the field of perinatal period were evaluated in good. No side effect was seen and an abnormal laboratory finding, the increase of GPT, was observed in only 1 case. LMOX was a highly useful antibiotic in perinatal infections, the safe dose range of LMOX into the perinatal mothers was estimated to be 2 g/day, with the maximum safe dose being 4 g/day.

Clinical studies were performed on the perinatal use of imipenem (IPM)/cilastatin sodium (CS). The obtained results are summarized as follows. 1. IPM/CS was administered to 11 perinatal infection cases which included mainly intrauterine infections and 3 mastitis cases in addition. IPM/CS showed excellent effectiveness against 1, good against 11, and the efficacy rates were 85.7%. 2. No side effects nor abnormal laboratory test values were observed.

Certain infections, such as UTI, may have an increased incidence during pregnancy owing to physiological changes. Between 2 and 10% of pregnant women have covert or asymptomatic bacteriuria which is associated with an increased incidence of acute symptomatic UTI in later pregnancy if left untreated. Thus antenatal screening to detect the presence of bacteriuria is justified. Most women will remain abacteriuric throughout the remainder of pregnancy after a single course of antibiotic therapy but a small percentage will fail to respond or have recurrent UTIs. Maternal infection with certain organisms, namely those which resist phagocytosis, may result in transplacental infection of the fetus in utero. Congenital syphilis is preventable and antenatal serological screening is usually routinely performed. Listeriosis following maternal infection in pregnancy is less predictable and the epidemiology of L. monocytogenes remains unclear. Genital tract carriage of sexually transmitted organisms, such as N. gonorrhoeae or C. trachomatis, may also be detected during pregnancy and antibiotic therapy will be indicated to eradicate such organisms and prevent maternal and neonatal morbidity. Antibiotic therapy during pregnancy will not, however, eradicate carriage of GBS from the genital tract, although carriage status at term can now be reliably predicted by using enriched culture techniques and swabbing multiple sites on more than one occasion. Where carriage is confirmed, the administration of intrapartum antibiotics to the mother appears a useful approach in the prevention of early onset neonatal GBS disease. Broad spectrum intrapartum antibiotics may also be indicated when there are complications, such as prolonged labour or premature rupture of membranes, which are associated with a higher incidence of maternal postpartum endometritis and morbidity than in women following uncomplicated vaginal delivery. Serious postnatal sepsis and shock is fortunately now rare. The pharmacokinetics of antibiotics in late pregnancy and the puerperium are altered and maternal serum levels may be reduced by 10-50%. Most antibiotics cross the placenta and are excreted in breast milk. Some agents, such as the beta-lactams, are considered safe in pregnancy and breast-feeding women while other antibiotics are contraindicated owing to risk of toxicity (often rare) or teratogenicity (often theoretical). Caution is necessary with many agents which may cause side effects or toxicity although this does not necessarily contraindicate their use in pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS) in the perinatal period were carried out, and the results obtained are summarized below. 1. IPM/CS transfers to umbilical cord plasma and amniotic fluid were effective. Passage of IPM/CS into mother's milk was as little as with other beta-lactam antibiotics. 2. Among 81 patients with perinatal infections, clinical efficacies were excellent in 16 patients, good in 62, poor in 3, with an efficacy rate of 96.3%. In addition, IPM/CS was effective in 6 patients for prophylaxis. 3. Out of 82 isolates examined for bacterial responses, 69 isolates were eradicated and 8 isolates were decreased. Especially, of 13 isolates of Enterococcus faecalis, 12 were eradicated. 4. In 109 patients administered with IPM/CS, vomiting was observed in 1 patient. No abnormal laboratory test values were observed. 5. IPM/CS was an effective and safe new antibiotic in perinatal infections. We recommend a normal dose of IPM/CS of 0.5 g/0.5 g twice a day and a dose for severe infections of 1 g/1 g twice a day in the perinatal period.

Efficacy and safety of ceftazidime (CAZ) in women during the perinatal period and their neonates were evaluated by a perinatal co-research group, and the results obtained were summarized as follows. Following an intravenous bolus injection or a drip infusion of CAZ from 1 g to 2 g, CAZ was transferred to maternal serum, umbilical cord serum and amniotic fluid rapidly and effectively. In 31 cases of perinatal infections, clinical efficacy was excellent in 10 cases, good in 18 and poor in 3, with an efficacy rate of 90.3%. In 85 cases given CAZ for prophylaxis of infections accompanying premature rupture of the membrane or following cesarean section, prophylactic effects were noted in 81 cases (efficacy rate: 95.3%). Neither adverse effects, nor abnormal laboratory findings were observed in any case. Also, no abnormalities in total serum bilirubin were observed in any neonates. From the above results, CAZ is considered to be a safe and useful drug for infections in women in perinatal period, usually in a unit dose of 1 g twice daily, or if necessary, 2 g twice daily.

Pharmacokinetic, bacteriological and clinical studies of imipenem/cilastatin sodium (IPM/CS) were carried out in the perinatal period, and the results obtained are summarized as follows: Effects of IPM on bacterial growth curves of Staphylococcus aureus (sensitive and resistant strains) and Escherichia coli (sensitive strains) in amniotic fluid were determined. The bactericidal effects of IPM increased in amniotic fluid and remarkable increases against resistant strains were demonstrated. IPM and CS were detected promptly after intravenous drip infusion to pregnant women, and reached peak levels shortly after administration in maternal plasma. Placental penetration of IPM and CS to the fetus was favorable. After intravenous drip infusion of 500 mg/500 mg of IPM/CS, drug concentrations in the umbilical cord plasma and the amniotic fluid exceeded MICs against main pathogenic organisms. Clinically, IPM/CS was effective in the treatment of perinatal infections without any side effect. The above results demonstrated that IPM/CS is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Pharmacokinetic studies and clinical evaluations of ceftazidime (CAZ) were carried out in perinatal mothers and infants, and following results were obtained. The CAZ was promptly absorbed after intravenous injection or intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transference to the fetus was good. After intravenous injection or intravenous drip infusion of 1.0-2.0 g of CAZ, drug concentration in umbilical serum and amniotic fluid exceeded MICs of CAZ against main pathogenic organisms. Levels of CAZ in umbilical serum ranged 0.2-15.6 micrograms/ml after 1.0 g intravenous injection or intravenous drip infusion, and 0.7-27.2 micrograms/ml after 2.0 g intravenous injection, and those in amniotic fluid were 1.4-21.3 micrograms/ml after 1.0 g administration and 2.0-27.0 micrograms/ml after 2.0 g administration. According to the above results, it is possible to successfully prevent or treat perinatal infections by twice a day administration of CAZ at 1.0-2.0 g/dose. Clinically, CAZ was effective in the treatment of perinatal infections and the prophylaxis of intrauterine amniotic infection without any side effect. Moreover, newborn infants delivered from mothers receiving CAZ treatment did not have any abnormalities in laboratory test. The penetration of CAZ into mother's milk was low, thus the transfer of CAZ from milk to newborn infants should be low. The above results demonstrated that CAZ is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

To evaluate the efficacy of imipenem/cilastatin sodium (IPM/CS) in the field of obstetrics and gynecology, fundamental (measurement of IPM/CS concentrations in mothers' milk) and clinical studies were performed. Concentrations of IPM/CS in mothers' milk were measured every 1 hour up to 6 hours after a 30-minute drip infusion of 500 mg/500 mg of IPM/CS. IPM/CS was distributed similarly to other cephalosporins. In the clinical study, a 500 mg/500 mg dose of IPM/CS was administered to 5 patients with puerperal intrauterine infections and to 3 patients with urinary tract infections by a 30-minute drip infusion b.i.d. or t.i.d. Good responses were observed in all 8 patients, though the infections were mild or moderate. From these results, IPM/CS appeared to be a useful drug for the treatment of perinatal infections.

Ceftriaxone (CTRX) was studied for its efficacy and safety in 8 cases of infection during the perinatal period; 6 before, and 2 after delivery. The results obtained are recognized as follows: 1. CTRX was administered by intravenous drip infusion at a daily dose between 2 and 4 g for 2 to 10 days (a total dose: 4 to 20 g) each of 8 cases of infections during the perinatal period; 3 of amniotic fluid infection and 1 each of intrauterine infection, puerperal fever, puerperal wound infection, appendicitis and pyelonephritis. CTRX was evaluated to be very effective in 3, effective in 3 and ineffective in 2, with an efficacy rate of 75% (6/8). 2. Two strains of Enterococcus faecalis and 1 each of Pseudomonas cepacia and Streptococcus intermedius were isolated. All of them were eradicated by the CTRX treatment bacteriologically. 3. No adverse reactions were observed subjectively or objectively. A slight transient elevation of GOT, GPT and Al-P was observed in 1 case. No abnormal sign was observed in neonates.

Gynecologic infections (primarily endometritis and pelvic inflammatory disease) in 73 women were evaluated for clinical and microbiologic response to treatment with aztreonam plus clindamycin or a control regimen. The dosage of aztreonam used most frequently was 1 g three times daily. For 72 of the 73 women, a microbiologic cure and a satisfactory clinical response were achieved. Twenty-three of the 73 patients were treated with aztreonam in an open study; all experienced a microbiologic cure and a favorable clinical response. Fifty of the 73 patients treated with aztreonam plus clindamycin were entered into a comparative study that included 38 patients who received gentamicin (3-5 mg/kg per day) plus clindamycin (600 mg three times a day). In 49 (98%) of the aztreonam-treated patients and in 36 (95%) of the gentamicin-treated patients, the causative organism was eradicated, and in 98% and 89% of the patients, respectively, a favorable clinical response was achieved.

Pharmacokinetic and clinical studies of ceftizoxime (CZX) in the perinatal period gave the following results: 1. Peak concentrations of CZX in the maternal serum, umbilical cord serum and amniotic fluid in mothers after one intravenous injection of 1 g were, respectively, 70.2 micrograms/ml at 0 hour; 15.7 micrograms/ml at 0.5 hour; and 10-30 micrograms/ml at 3-6 hours. Concentrations of CZX in the neonatal serum were 0.87-13.5 micrograms/ml during 6-14 hours after parturition. The mean concentration of CZX in the milk in 1-8 hours after injection was less than 0.32-0.52 microgram/ml. 2. Good or excellent clinical efficacy was obtained in 28 of the 29 patients with perinatal infections, with an efficacy rate of 96.6%. Prophylactic effectiveness was obtained in 14 of the 15 patients, with an efficacy rate of 93.3%. 3. No side effects were observed in 44 cases. GOT and GPT values increased slightly in 1 patient. No abnormal values in total serum bilirubin or other parameters were found in any neonates after parturition. 4. The above results suggest that CZX is safe and effective for the treatment and prophylaxis of infection in the perinatal period.

The antianaerobic cephalosporins, cefoxitin, ceftizoxime, cefotetan, and moxalactam, are compared in the treatment of obstetric/gynecologic infections associated with mixed aerobic and anaerobic pathogens. All of the antianaerobic cephalosporins have demonstrated similar efficacy in the treatment of mixed female genital tract infections. Thus, antibiotic selection requires a comparison of the antimicrobial activity, pharmacokinetics, adverse effects, and overall cost of therapy. All agents have excellent activity against the Gram-negative bacilli, and recent comparative data show that ceftizoxime is highly active against the Bacteroides sp. Dosing frequency and drug toxicity contribute to the overall cost of drug therapy. Cefoxitin is the only antianaerobic cephalosporin that cannot be dosed on a 12-hour basis. Ceftizoxime and cefoxitin, unlike moxalactam and cefotetan, do not contain the MTT group that has been associated with bleeding abnormalities. Substantial cost savings can be realized by using an antianaerobic cephalosporin administered every 12 hours. The experience at the Chicago Lying-in Hospital is presented.

Fundamental and clinical studies of cefotaxime (CTX) were carried out in pregnant women. The following results were obtained. CTX was more rapidly eliminated from the serum of pregnant women than that of adult males. Urinary excretion of CTX in pregnant women was comparable to that in nonpregnant women and adult males. Passage of CTX to the embryo, fetus and fetal appendages was minimal. Peak amniotic fluid concentration (9.8 mcg/ml) was attained at 3.5 hours after administration of CTX and gradually declined thereafter. This amniotic fluid concentration was sufficiently higher than reported MIC90 of CTX against E. coli strains. CTX was used in the treatment of 6 pregnant patients with acute pyelonephritis and 2 with puerperal infections. The bacteriological and clinical responses were both 100%. Since passage of CX into the amniotic fluid is favorable, CTX can be expected to be effective for the prophylaxis of intrauterine amniotic infection associated with early rupture of the membrane. CTX was used in the treatment of a neonate with purulent meningitis. The clinical response was effective. CTX did not cause any noteworthy adverse reactions or laboratory data abnormalities in our patients or neonates.

The placental passage and therapeutic efficacy of imipenem/cilastatin sodium (IPM/CS) were studied in the perinatal period. The results obtained are summarized as follows: 1. The mean biological half-life of IPM in maternal serum was 30 minutes. 2. The umbilical cord serum concentration of IPM was about 70% of that in maternal serum after 30 minutes. 3. A significant level of IPM was found in the amniotic fluid. The amniotic fluid concentration of IPM was over 1 micrograms/ml at 45 minutes after administration and equal to that in maternal serum at about 90 minutes. 4. In 4 patients, the time course of placental transfer of IPM was investigated. The level of IPM in amniotic fluid was higher than that in maternal serum at 90 minutes after administration and gradually increased afterward. 5. The level of IPM was 3.96 micrograms/g in the fetal membranes at 17 minutes after administration. 6. In the treatment of 12 patients with perinatal infections, the preparation showed excellent efficacies in 3 patients and good efficacies in 7 patients. 7. An adverse effect (vomiting) was observed in only one patient. In conclusion, this drug showed satisfactory placental transfer as well as sufficient safety and excellent efficacy in the treatment of perinatal infections.

Ceftazidime (CAZ), a new cephem antibiotic with high activity against Gram-negative bacteria, has been investigated for use in mothers in perinatal period, and the results obtained are summarized below. Into maternal serum, umbilical cord serum and amniotic fluid, CAZ showed good transfer after intravenous administration of 1 g or 2 g into mothers, and no adverse effect appeared in their neonates. The CAZ is a very useful antibiotic for the prophylaxis and the treatment of perinatal infections at a dose level of 1-2 g per day.

The use of antimicrobial agents during pregnancy poses unique concerns because of both potential toxicity and special pharmacokinetic considerations that have important therapeutic implications for both mother and fetus. Various physiologic adaptations occur with advancing gestation, including marked increases in maternal intravascular volume, glomerular filtration, and hepatic and metabolic activities; thinning and maturation of the fetomaternal membrane; and increases in transplacental diffusion capacity. The net result is that maternal antimicrobial concentrations tend to be 10%-50% lower in late pregnancy and the immediate postpartum period than in the nonpregnant state. Placental transfer of antimicrobial agents and their excretion in amniotic fluid or breast milk are similarly affected by hemodynamic changes, membrane transport characteristics, and maturation or metabolic activity of the specific organs involved. Review of the literature suggests that, although the need for caution in the use of antimicrobial agents during pregnancy has been well emphasized, firm data on the pharmacokinetics, efficacy, and optimal use of these drugs in this situation are extremely sparse and urgently needed. However, recommendations regarding the use of specific antibacterial, antifungal, antiviral, and antiparasitic agents against selected infections during pregnancy can be made.

The streptococcus, responsible for inestimable morbidity and mortality among parturient women since the 16th century, is no longer a significant cause of puerperal infection. Although the problem of the group A streptococcus in obstetrics has abated, the obstetrician is now confronted with the group B streptococcus, which is a major cause of fetal, neonatal, and maternal morbidity and mortality. Some historical insight into the infectious disease problems encountered by obstetric practitioners during the last four centuries allows comparison and contrast between the historic scourge of childbed fever and present day obstetric infections.

Clinical studies were carried out on imipenem/cilastatin sodium (IPM/CS) in the perinatal period, and the results are summarized below. 1. IPM/CS was administered to a total of 10 patients including 7 with puerperal intrauterine infections and 3 with pyelonephritis at a dose of 0.5 g/0.5 g twice daily through intravenous drip infusion. IPM/CS showed satisfactory results. Clinical efficacies were excellent in 1 patient, good in 9 with an efficacy rate of 100%. 2. As for bacteriological evaluation, 12 strains out of 14 detected in 8 patients before the treatment were eradicated upon IPM/CS administration, with an eradication rate of 85.7%. The remaining 2 strains persisted. 3. Neither subjective and objective side effects nor abnormal laboratory test values were observed in any of the patients or their babies.

Pharmacokinetic and clinical studies were carried out on the use of ceftizoxime (CZX) in the perinatal period. The results obtained are summarized below. 1. Mean maternal serum concentrations of CZX reached 57.3 micrograms/ml at about 15 minutes after a single intravenous injection of CZX 1 g and then gradually decreased to 13.1 micrograms/ml in 1 hour and 55 minutes, 3.59 micrograms/ml in 4 hours and 20 minutes and 0.11 microgram/ml in 17 hours and 51 minutes. CZX in umbilical cord serum was at detectable concentrations soon after administration and peaked to 23.5 micrograms/ml in 32 minutes. Although the concentrations in umbilical cord serum gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and more after an injection and was 0.41 microgram/ml at 17 hours and 51 minutes. The CZX in amniotic fluid became detectable a little later than CZX in umbilical cord serum. The concentration of CZX in amniotic fluid was below 1.00 microgram/ml at 30 minutes after administration. Concentrations then gradually increased to 21.3 micrograms/ml in 1 hour and 55 minutes and, even in 17 hours and 51 minutes, they were as high as 9.44 micrograms/ml. 2. In the clinical evaluation, CZX was given to a total of 7 cases, i.e., 1 of amnionitis, 2 of puerperal endometritis, 1 of puerperal fever, and 3 of pyelonephritis. The treatment showed satisfactory results, i.e. excellent result was obtained in 1 case, good in 5 and poor in 1 with an clinical efficacy rate of 85.7%. Microbiological examinations resulted in the isolation of 5 bacterial strains of 4 species and 1 fungal strain from 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotiam (CTM), a new cephem antibiotic with high activity against Gram-positive and Gram-negative bacteria, has been investigated for use in 60 mothers in perinatal period, and following results were obtained. The concentration of CTM in maternal serum was 38 micrograms/ml at 0.5 hour after an intravenous administration of 1 g. A good transport of CTM into umbilical cord serum and amniotic fluid was observed after the intravenous administration into the mother. No adverse effect appeared in the neonates. The CTM is highly useful antibiotic in perinatal infections, and the safe dose of CTM to the mother in perinatal period is considered to be 1-2 g per day.

Metronidazole which has been widely used in the treatment of trichomoniasis urogenitalis is the most active agent available against obligate anaerobes.--In this review the present data about antimicrobial activity, mode of action, pharmacokinetic behaviour, dosage, clinical use in gynecology and obstetrics and side effects of metronidazole are outlined.