Meropenem versus imipenem-cilastatin for the treatment of hospitalized patients with complicated skin and skin structure infections: results of a multicenter, randomized, double-blind comparative study.

BACKGROUND: Meropenem, a broad-spectrum carbapenem with potent in vitro activity, is postulated to be an effective monotherapy for the treatment of complicated skin and skin structure infections (cSSSI). METHODS: This multicenter, international, double-blind, randomized, prospective study of hospitalized patients with cSSSI evaluated the efficacy, safety, and tolerability of meropenem (500 mg IV q8h) versus imipenem-cilastatin (500 mg IV q8h). The primary efficacy endpoint was clinical outcome at follow-up in the clinically evaluable (CE) and modified intent-to-treat populations (MITT; patients who met eligibility criteria and received at least one dose of study drug). The study aimed to demonstrate non-inferiority (delta of 10%, 95% confidence intervals) in clinical response in the CE population. Clinical responses for all pathogens at follow-up were assessed in the fully evaluable population (CE population with baseline pathogen and follow-up cultures). RESULTS: In total, 1,076 patients were enrolled. Of these, 692 patients comprised the MITT population (334 and 358 patients randomized to meropenem and imipenem-cilastatin, respectively) and 548 the CE population (261 and 287 patients randomized to meropenem and imipenem-cilastatin, respectively). Cure rates were 86.2% (meropenem) and 82.9% (imipenemcilastatin; 95% CI, -2.8, 9.3) in the CE population and 73.1% (meropenem) and 74.9% (imipenem-cilastatin; 95% CI, -8.4, 4.7) in the MITT population. The frequencies of adverse events and drug-related adverse events were similar between treatment groups. CONCLUSION: In one of the largest studies conducted to date of hospitalized patients with cSSSI, meropenem, 500 mg IV q8h had comparable safety and efficacy to imipenem-cilastatin, 500 mg IV q8h.

The fibula free flap: advantages of the muscle sparing technique.

The amount of muscle that should be retained on the free fibula during harvest is unresolved. Muscle is used to protect the periosteum, but by harvesting a large muscle cuff, the recipient and donor site morbidity increases. A retrospective review of 47 free fibula flaps performed between January 1997 and March 2002 was undertaken. There was an average follow-up of 15 months. The dissection method used for all cases was a muscle sparing technique where the peroneal vessels were skeletonised anteromedially. Only a very thin rim of muscle (1-2 mm) was left attached to the fibula. The recipient and donor vessels were flushed with heparin saline solution intra-operatively and a Dextran 40 infusion was used for four days post-operatively in all cases. Of the 47 flaps, 39 were used for mandible reconstruction, six for maxillary reconstruction and two for long bone reconstruction following trauma. The average age was 47.7 years (range 13-82) and two-thirds (28/43) of the patients were male. There was one post-operative death. The overall failure rate was 10.9% (5/46). Two flaps were lost as a result of arterial thrombosis, one from venous thrombosis, one from sepsis and in one case the cause could not be determined. There were 2 (4.3%) recipient site haematomas. It is suggested that the low recipient site haematoma rate in this series may be related to the limited muscle bulk transferred with the flap. Harvesting less muscle also enables easier insetting and folding of skin flap, and reduces the donor site problems of haematoma and weakness of the foot. The blood supply to the fibula does not appear to be compromised.

Study on the origin of seminal leucocytes using split ejaculate technique and the effect of leucocytospermia on sperm characteristics.

The origin of seminal leucocytes and their biological significance were investigated in 76 whole ejaculate samples and 27 split ejaculate samples, obtained from patients attending the Zimbabwe Family Planning Council's Spilhaus Infertility Clinic at Harare. The leucocytes were more prevalent in fractions 1 and 2 than in fraction 3, implying that the testis, epididymis and prostate are the major sources of seminal leucocytes. The contribution from the seminal vesicles was minimal. An inverse relation is apparent between leucocyte count and sperm count (p < 0.01). The percentage of abnormal sperms was higher (p < 0.05) and the sperm motility poorer in leucocytospermic samples (p < 0.01). Fructose, the seminal vesicular marker, citric acid, the prostatic marker and alpha-glucosidase, the epididymal marker were not decreased in leucocytospermia. It is concluded that the epididymis and prostate are the major contributors of granulocytes in semen. Leucocytospermia affects sperm morphology and sperm motility but not the accessory sex gland functions. Probably these cytotoxic effects are mediated by hydrogen peroxide due to activation of seminal leucocytes. However, the presence of leucocytospermia in normozoospermic samples is indicative of the possible peaceful coexistence of leucocytes and sperms.

Randomised controlled trial of intrapartum fetal heart rate monitoring.

OBJECTIVE: To compare effectiveness of different methods of monitoring intrapartum fetal heart rate. DESIGN: Prospective randomised controlled trial. SETTING: Referral maternity hospital, Harare, Zimbabwe. SUBJECTS: 1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study. INTERVENTIONS: Intermittent monitoring of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard stethoscope by a research midwife, or routine use of Pinard stethoscope by attending midwife. MAIN OUTCOME MEASURES: Abnormal fetal heart rate patterns, need for operative delivery for fetal distress, neonatal mortality, Apgar scores, admission to neonatal unit, neonatal seizures, and hypoxic ischaemic encephalopathy. RESULTS: Abnormalities in fetal heart rate were detected in 54% (172/318) of the electronic monitoring group, 32% (100/312) of the ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9% (28/315) of the routine monitoring group. Caesarean sections were performed for 28% (89%), 24% (76), 10% (32), and 15% (46) of the four groups respectively. Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic encephalopathy occurred in two, one, seven, and 10 cases in the four groups respectively; neonatal seizures occurred only in the last two groups (six and nine cases respectively); and deaths occurred in eight, two, five, and nine cases respectively. CONCLUSIONS: Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope, and its use resulted in good perinatal outcome. The use of relatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources.

Intrapartum foetal heart rate monitoring--continuous electronic versus intermittent Doppler--a randomised controlled trial.

OBJECTIVE: To compare different methods of intrapartum foetal heart rate monitoring in high risk pregnancies in detecting foetal heart rate abnormalities, need for operative delivery for foetal distress, and neonatal mortality and short term neonatal morbidity. DESIGN: A prospective randomised controlled trial. SETTING: Women in labour at a referral maternity hospital. PATIENTS: Women who were 37 weeks or more pregnant with singleton cephalic presentation and normal foetal heart rate prior to entry into the study. INTERVENTION: Women were randomly allocated using sealed opaque envelopes to either continuous electronic foetal heart rate monitoring or intermittent monitoring using hand held doppler foetal heart rate detector. OUTCOME MEASURES: These include abnormal foetal heart rate patterns, need for operative delivery for foetal distress, neonatal mortality, Apgar scores, admission to NNU, neonatal seizures, and hypoxic encephalopathy. RESULTS: Randomisation achieved good comparability between the two groups. Abnormal FHR patterns were more frequent in the electronic group (54 pc versus 32 pc). Caesarean section rate was not significantly different in the two groups (28 pc versus 24 pc) although slightly higher compared to overall for the unit (18pc). Foetal outcome was also comparable between the two groups. CONCLUSIONS: Asphyxia can be detected with a hand held doppler just as reliably as by the use of electronic monitors and their use should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources.