Prevalence and distribution of plasmid-mediated quinolone resistance genes in clinical isolates of Escherichia coli lacking extended-spectrum beta-lactamases.

OBJECTIVES: The aac(6')-Ib-cr gene has been described in plasmids from CTX-M-15-producing Escherichia coli in the worldwide ST131 lineage, but has not been systematically sought in other quinolone-resistant strains in the UK. A rise in quinolone resistance in bacteraemia isolates in the UK preceded the increased prevalence of CTX-M-producing strains. This study aimed to describe the presence of plasmid-encoded quinolone resistance genes in historical and current strains of E. coli not producing extended-spectrum beta-lactamases (ESBLs). METHODS: Ciprofloxacin-resistant, non-ESBL-producing E. coli isolates included nationally distributed isolates from the BSAC UK bacteraemia surveillance programme between 2001 and 2005, urinary isolates from a regional project in 2000 and local strains in 2006. The aac(6')-Ib-cr gene was detected using PCR followed by restriction fragment length polymorphism analysis. Multiplex PCR was used to detect qnr genes. Isolates with aac(6')-Ib-cr were assessed for aminoglycoside susceptibilities and were serotyped. RESULTS: The prevalence of the aac(6')-Ib-cr gene was 3% and 9% in current local urinary and historic national bacteraemia quinolone-resistant non-ESBL-producing E. coli, respectively. Of 521 regional urinary E. coli isolates from 2000, 14 were norfloxacin-resistant, none of which carried the aac(6')-Ib-cr gene. National positive bacteraemia isolates from 2001/2 were type O102-ST405 and, in 2004/5, types O1-ST645 and O25-ST131. Positive local urinary isolates from 2006 included serotypes O1 and O25. CONCLUSIONS: In the UK, aac(6')-Ib-cr occurs in E. coli in the absence of CTX-M-15, but with a restricted serotype distribution. Its presence in widespread bacteraemia isolates of a single type from 2001 to 2002, prior to the spread of CTX-M-15 in Britain, might suggest a lineage from which plasmid recombination occurred in man or other species.

A comparison of high versus low dose recombinant human erythropoietin versus blood transfusion in the management of anaemia of prematurity in a developing country.

The purpose of this study was to evaluate the effectiveness of early treatment with erythropoietin (EPO) in two different treatment regimes (high vs. low dose) in comparison to the conventional treatment of packed red blood cell (PRBC) transfusions in the management of anaemia of prematurity in a country with limited resources. An open controlled trial was conducted on 93 preterm infants (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group. EPO was administered subcutaneously three times a week and all infants received 6 mg/kg iron orally from study entry to endpoint of therapy. Haematological parameters were measured and compared. The success was defined as an absence of transfusions and a haematocrit that did not fall below 30 per cent during the time period that the infants were in the study. The three groups were statistically comparable at study entry with respect to gestational age, birthweight, Apgar scores, and haematological values. Over the period that the infants were in the study, 75 per cent of the low dose group and 71 per cent of the high dose group met the criteria for success compared with 40 per cent in the control group (p < 0.001). However, there was no significant difference in the number of transfusions when the low and high EPO dose groups (9.5 per cent) were combined and compared with the control group (26.7 per cent) p = 0.0587. It was concluded that in stable infants, 900-1500 g, where phlebotomy losses are minimized and stringent transfusion guidelines are adhered to, EPO does not significantly decrease the number of transfusions. A conservative approach in the management of anaemia of prematurity, is a viable alternative in areas with limited resources.

Factors associated with poor prognosis in very-low-birth-weight infants.

OBJECTIVE: To evaluate predictors of poor outcome, including the CRIB (Clinical Risk Index for Babies) score, in a local population of very-low-birth-weight (VLBW) infants, in order to provide guidelines for selection of these babies for expensive tertiary care. SUBJECTS: Two hundred and thirty-one neonates born at less than 31 weeks' gestation and/or weighing between 1001 g and 1500 g, enrolled prospectively as part of a multicentre study evaluating the CRIB score. DESIGN: Univariate analysis (chi-square/t-tests) and multivariate analysis (stepwise logistic regression) on the above sample to determine predictors of poor outcome. SETTING: Neonatal Unit, Johannesburg Hospital. OUTCOME MEASURES: Death or impairment (namely oxygen therapy > 28 days, grade 3 or 4 intraventricular haemorrhage, or ventricular enlargement). RESULTS: Poor outcome was predicted by birth weight, lowest oxygen requirement in the first 12 hours (which are two components of the CRIB score), and maximum partial arterial carbon dioxide pressure (PaCO2) in the first 72 hours. Other factors, including the full CRIB score, were not predictive of outcome. CONCLUSIONS: One method of selection of infants for expensive tertiary care is on the basis of predicted outcome. Birth weight remains a reasonable basis for this selection, but the inclusion of other factors, such as oxygen requirement, would improve accuracy. The CRIB score was not a suitable means to select infants in the local context, but may be of value in international comparisons.

Selection of paediatric patients for intensive care.

OBJECTIVES: To determine characteristics of older infants and children admitted to the paediatric intensive care unit (PICU) at Johannesburg Hospital; and to evaluate an admission score based on the PRISM score (an index of severity of illness) as a possible means for selection of patients for admission to the PICU. DESIGN: Retrospective review of patient records and calculation of admission score from data. SETTING: Paediatric intensive care unit at Johannesburg Hospital. SUBJECTS: All patients older than 3 months of age admitted to the PICU from July 1993 to 31 March 1994. RESULTS: There were 117 admissions during the study period with a mean age of 4,6 years. The mortality rate was 29.1%. The mean duration of ICU stay was 4,2 days. A review of requests for admission showed that over a 7-month period, 53 patients (> 3 months) could not be accommodated. In 71 patients with complete data, the admission score was significantly higher in non-survivors than survivors. The area under the ROC curve for predicting mortality from the admission score was 0.73 (SE 0.054). An admission score > or = 16 predicted mortality with a sensitivity of 42% and a specificity of 98%. CONCLUSIONS: PICU facilities at Johannesburg Hospital are insufficient to meet the demand. An admission score based on the PRISM score could assist in the selection of patients for these limited PICU facilities.

The introduction of surfactant replacement therapy into South Africa.

Within the context of limited financial and physical resources in South Africa, academic neonatologists have established strict criteria for ventilation of neonates with hyaline membrane disease (HMD). In the private sector neonatal care is less structured. Following the introduction of the artificial surfactant (Survanta) in November 1991 it was considered important to monitor its use in the public and private sectors. In collaboration with the marketing company a data sheet containing demographic information and clinical details was drawn up to be completed in each case where Survanta was administered to babies with HMD. Data from 155 babies treated at 10 hospitals were included in the final analysis (70 babies from 4 State-funded academic hospitals and 85 from 6 privately funded hospitals). Within the group of private hospitals there were some which treated large numbers of babies weighing > 2,000 g, while in a few others there was a relative excess of babies weighing < 1,000 g. There was a higher incidence of patent ductus arteriosus and intraventricular haemorrhage, and a higher mortality rate at the academic hospitals. Poor outcome at these institutions may largely have been due to poor antenatal care.

The selection of infants for surfactant replacement therapy under conditions of limited financial resources.

The cost of surfactant replacement therapy (SRT) will restrict its use under conditions of limited health resources. Before the local advent of SRT, infants ventilated for hyaline membrane disease (HMD) had an overall survival rate of 87% and an incidence of bronchopulmonary dysplasia of 6.4%. This, together with the cost of SRT, prompted a study to identify those infants who would benefit the most from SRT. Twenty-two infants assessed as having severe HMD were randomised to receive SRT at 3 - 4 hours (9) or at 6 - 8 hours (13) after birth. Two infants (15%) in the latter group did not require SRT. The outcome of these two groups was the same. Of 56 infants assessed as having moderate HMD, only 24 (43%) qualified for SRT from 6 hours of age. The outcome of the SRT and non-SRT infants was comparable. The group of infants with moderate HMD had a significantly better outcome than those with severe HMD. A limited period of observation to assess the severity of illness did not compromise outcome in this group of 78 infants with moderate to severe HMD.

The cost and effectiveness of surfactant replacement therapy at Johannesburg Hospital, November 1991-December 1992.

OBJECTIVE: To assess the impact of surfactant replacement therapy (SRT) on the outcome of hyaline membrane disease (HMD) and to assess the cost implications of a policy of selective administration of artificial surfactant. DESIGN: The short-term outcome of 103 newborns ventilated for HMD (61 selected for SRT according to initial and/or ongoing oxygen requirements) was compared with that of a historical control group of 173 infants ventilated for HMD before the introduction of SRT. MAIN OUTCOME MEASURES: Mortality and morbidity of HMD including death, bronchopulmonary dysplasia, pneumothorax, pulmonary haemorrhage, patent ductus arteriosus and intraventricular haemorrhage. RESULTS: There were significant demographic differences between the treatment and control groups (black patients 74% v. 28%, P < 0.0001; unbooked mothers 72% v. 15%, P < 0.0001) as well as evidence of more severe lung disease in the treatment group (pressor support 44% v. 27%, P < 0.005; and paralysis during ventilation 38% v. 25%, P < 0.005). Pneumothorax was reduced in the SRT group (7% v. 17%, P < 0.01). There were no significant differences between the two groups in the incidence of BPD or mortality. The use of SRT added to the total cost of treating a patient ventilated for HMD. CONCLUSION: The selective use of SRT had the effect of converting severe disease into moderate disease rather than achieving maximal benefit in all cases of HMD through routine use of the product. A policy of restricting use may result in cost savings where resources are limited.

The late administration of surfactant.

Current recommendations for surfactant replacement therapy (SRT) in the treatment of hyaline membrane disease (HMD) are to administer the drug as soon as possible after starting ventilation in order to prevent ventilator lung damage. We present a review of 18 infants (gestational age 32.4 +/- 1.9 weeks and birth weight 1,795 +/- 427 g) who received the initial dose of SRT after they were 12 hours old. Fourteen infants were assessed as having HMD and 4 as having congenital pneumonia. Overall there was a significant and sustained improvement in oxygenation as measured by arterial/alveolar oxygen ratios. The outcome of these infants was good, with a duration of ventilation of 7.9 +/- 4.3 days and a duration of hospitalisation of 26.2 +/- 12.6 days. No infant developed bronchopulmonary dysplasia. Of particular interest is that 3 infants weighing > 2,400 g with congenital pneumonia responded to a single delayed dose of SRT. Late SRT is effective and there may be a place for SRT in the treatment of conditions other than HMD.

Prevalence of hyaline membrane disease in black and white low-birth-weight infants.

Previous studies in South Africa and elsewhere have suggested that there are ethnic differences in the prevalence of hyaline membrane disease (HMD). This study compared the prevalence of HMD between black and white infants with birth weights of 1,000-1,749 g. A cohort of black and one of white low-birth-weight infants were enrolled at Baragwanath and Johannesburg Hospitals respectively. Black infants were found to have a higher rate of intra-uterine growth retardation. When compared according to either birth weight or gestational age categories, black infants had a significantly lower prevalence of HMD. For example, between 29 and 34 weeks' gestation 36.2% of black and 62.5% of white infants developed HMD (P < 0.001). The reasons for these differences are not clear, however, and require further study.

Bandwidths of respiratory gas flow and pressure waveforms in mechanically ventilated infants.

The frequency content of airway pressure and gas flow in mechanically ventilated infants (MVIS) has not been adequately investigated. Pressure-cycled infant ventilators generate pressure pulses with short rise-times. Gas flow is approximately equal to the derivative of pressure when lung compliance is low, and hence contains high-frequency components. We defined bandwidth as that frequency fm below which 99.9% of the energy of the signal resided. Simulation of the measurement process using measurement systems with frequency response similar to sixth-order Bessel filters and a lung model comprising series resistance, inertance and compliance showed that measurement systems with frequency response flat +/- 10% to fm yield time domain errors less than 3% of the peak value. We digitized pressure and flow signals from 10-20 ventilator (Healthdyne 105) breaths in 33 stable MVIS. The transducers' (Gould P50, Hans Rudolph 8300 screen pneumotach) frequency responses had been measured between 1 Hz and 100 Hz and phase matched at 10 Hz. We calculated total respiratory resistance R and elastance E using multiple linear regression, and ensemble-average power spectral density using the FFT with a rectangular time window and padding to 2048 points. Power spectra were compensated for non-unity transducer and anti-alias filter responses up to 60 Hz. Measured data sequences that were not self-windowing due to spontaneous breathing efforts, that yielded regression R2 < 0.95 or that contained flow oscillations due to secretions in the airway were discarded. Satisfactory results were obtained from more than eight breaths in 18 infants. Mean bandwidths (+/- SD) of pressure and flow waveforms were 4.7 +/- 0.7, range 3.5-5.9 and 19.6 +/- 6.5, range 10.8-32.1 Hz, respectively. Flow bandwidths B correlated with the respiratory time constant tau (B = -77.2 tau + 26.8, R2 = 0.55, P < 0.0002), and with elastance E (B = 61.4E + 10.1, R2 = 0.74, P < 0.0001). We conclude that the bandwidth of the flow waveform increases with decreasing compliance and mechanical time constant. The frequency response of pressure and flow measurement systems should be flat +/- 10% at least up to 6 and 32 Hz respectively to obtain data with dynamic errors less than 3% in infants with low-compliance lung disease.

Does hypoxemia prevent brain damage in birth asphyxia?

The clinical syndrome of hypoxic ischemic encephalopathy (HIE) which occurs in association with birth asphyxia, is thought to represent a reperfusion injury consequent upon the generation of cytotoxic oxygen derived free radicals. It has recently been suggested that resuscitation of asphyxiated infants with unrestricted oxygen may aggravate the brain damage by causing hyperoxia and increased free radical production. To determine whether sustained hypoxemia may be protective in birth asphyxiated infants, we investigated the relationship between HIE and persistent pulmonary hypertension of the neonate (PPHN). The latter condition is also related to intrauterine and intrapartum birth asphyxia but is associated with persistent hypoxemia in the infant. In a retrospective analysis of 39 asphyxiated neonates admitted to the neonatal intensive care unit, we found that 28 had HIE, 10 had PPHN and only 1 had both HIE and PPHN. We therefore suggest that the hypoxemia due to PPHN may limit the production of oxygen derived free radicals in asphyxiated neonates and hence protect against the development of HIE. These findings lend support to current research into air vs. oxygen resuscitation for infants with birth asphyxia.

Severe illness caused by Rickettsia conorii.

An 18-month-old boy presented with a 5-day history of lethargy, fever, vomiting and rash. He required intensive care for inotropic and ventilatory support. He developed a disseminated intravascular coagulopathy and gangrene of his extremities. In addition, he had severe neurological dysfunction and loss of vision, both of which recovered spontaneously with time. The potential severity of tick typhus caused by Rickettsia conorii is described as well as the importance of paired serological tests in the diagnosis of this condition.

Non-ketotic hyperglycinaemia in a neonate. A case report.

Non-ketotic hyperglycinaemia was diagnosed in a newborn infant presenting with lethargy, apnoea, hiccoughs and myoclonic seizures. The typical findings of raised cerebrospinal fluid:plasma glycine ratio, a burst suppression pattern on electro-encephalography, hypodense areas seen on computed tomography and lack of acidosis, ketosis and serum organic acid abnormality confirmed the diagnosis. Prenatal diagnosis by investigating the glycine cleavage enzyme system from a chorionic villus sample is not yet available.

Short-term outcome for very-low-birth-weight infants with prolonged oxygen requirement.

Although Johannesburg Hospital's neonatal intensive care unit's survival rates are similar to those of First-World countries, it has been the impression of ward staff that ventilated very-low-birth-weight (VLBW) infants who cannot be weaned from high concentrations of oxygen and/or high inflation pressures within 7-10 days constitute a group with a poor prognosis. This study confirms previous studies showing that the early neonatal mortality rate is twice as high as the late neonatal mortality rate. It also confirms that mortality is related to birth weight and peak pressure and shows that VLBW infants with high oxygen and pressure requirements after 1 week do indeed constitute an extremely high-risk group with a short-term morbidity rate of 70-80% and a mortality rate of almost 50%.

Dynamic skinfold measurements to assess fluid status in low birthweight infants. Part 1: Data acquisition and processing.

To evaluate the measurement of fluid status in the premature neonate using dynamic skinfold thickness (DST) measurement, a pair of calipers were interfaced to a computer, and weight and digital DST at four sites were measured daily in 24 neonates in the postnatal weight loss period. A biexponential equation was fitted to each curve from the instant the rate of caliper closure fell below 2 mm/s, and the five constants obtained used in a search for a parameter that correlated with the percentage of weight loss. The percentage of fall in the DST from 0.4 to 30 seconds yielded highest mean of individual coefficients of determination (COD) (0.83); the percentage of fall from 0.7 to 35 seconds yielded highest COD in pooled data (0.56). Expected weight loss can be predicted with standard error of 2.9% with pooled regression but with standard error of 1.3% using individual correlations. We conclude that individuals lose fluid in a consistent manner during this period but that interindividual differences are large and require further investigation.

Dynamic skinfold measurements to assess fluid status in low birthweight infants. Part 2: Correlation with postnatal weight changes.

Computerized recording of dynamic skinfold thickness measurements was performed on low birthweight infants. Four skinfold sites were measured daily for the first 7 days postnatally and then at intervals up to 4 weeks of age. The percentage of fall of the skinfold between 0.4 and 30 seconds after caliper application was shown to correlate best with postnatal weight loss until minimum weight was reached. Of the 24 infants studied in detail, only two had a correlation coefficient less than 0.75 between changes in the percentage of fall of the skinfold and postnatal weight changes. There was, however, marked individual variation in the amount of weight loss for a given reduction in the percent of the skinfold. Assuming that most of the postnatal weight loss of low birthweight infants is due to reduction of extracellular volume, dynamic skinfold thickness appears to be a good noninvasive measure thereof.

Three-year growth and developmental follow-up of very low birth weight infants fed own mother's milk, a premature infant formula, or one of two standard formulas.

A cohort of 40 very low birth weight (VLBW) infants was followed until they reached 3 years of age. These infants were originally part of a feeding trial in the early postnatal period whereby they were fed either their own mother's milk, a standard whey-predominant formula, a casein-predominant formula, or a premature formula. Those fed the latter formula grew significantly better while in the hospital and had no biochemical derangements. At 3 years of age, there were no significant intergroup differences with respect to growth or development. There was a positive correlation between head growth in hospital and weight at 3 years, but there were no other significant relationships between early postnatal growth and growth parameters at 3 years. Socioeconomic status was the only predictor of developmental scores at 3 years of age. No adverse effects from early metabolic acidosis or alterations of amino acid profiles during the neonatal period were detectable at 3 years of age. However, the small sample size of this study may have missed true differences in outcome measures at 3 years, and larger studies are required to examine these questions further.

Needs for special-care beds for the newborn in the Witwatersrand area.

The requirements for different levels of neonatal care in the Witwatersrand area were estimated from a review of neonatal unit records of all infants born at Johannesburg Hospital during 1983 and 1984. When extrapolating these figures to the greater population of the Witwatersrand and referral areas, adjustments were made for the increased number of low-birth-weight and complicated deliveries at Johannesburg Hospital. Given the low-birth-weight rate of 8% for this population, it was calculated that 3.3 intermediate-care beds and 1.2 intensive-care beds were justified per 1,000 annual live births. A total of 25 beds for mechanical ventilation of neonates were required over this study period, approximately double the number available. Facilities for other population groups, who have higher rates for low birth weight, were even less adequate. For the country as a whole it is recognised that postneonatal mortality is a greater problem amenable to less costly intervention than neonatal mortality; nevertheless, existing facilities for neonatal care should be used more efficiently, and a co-ordinated regional service for all population groups in the area should be established.

Comparative growth and biochemical response of very low birthweight infants fed own mother's milk, a premature infant formula, or one of two standard formulas.

Very low birthweight (VLBW) infants weighing less than 1,600 g at birth were fed their own mother's milk (OMM) or randomly assigned to receive one of three formulas: a "humanized" formula (SF), a partially modified casein-predominant cow's milk formula (CF), or a premature formula (PF). All infants were fed at 120 kcal/kg/day where possible. PF infants had significantly greater weight increments (28.0 g/day) than those on OMM (19.4 g/day), SF (18.9 g/day), and CF (18.2 g/day). Those on PF also had greater increments of length, head circumference, and skin-fold thickness than those on the other two formulas and greater length increments than those on OMM. Dynamic skinfold measurements suggested that no infants accumulated excessive amounts of interstitial fluid. Infants on the two standard formulas had significantly greater base deficits, whereas those on CF also had higher urea values. Those on OMM had lower phosphate and higher alkaline phosphatase values than the other groups. Thus VLBW infants fed a premature formula had better growth and fewer biochemical problems than those on standard formulas, whereas supplementation of OMM may be necessary to ensure optimal growth and bone mineralization.

A comparison of two resuscitators in the management of birth asphyxia.

Twenty newborn infants with birth asphyxia were alternately assigned to ventilation with either the Samson or the Laerdal infant resuscitator. During resuscitation significantly greater percentage changes in pH (1,1% v. 0,2%; P less than 0,05), hydrogen ion concentration (-15,6% v. -2,1%; P less than 0,05) and partial arterial carbon dioxide pressure (-24,5% v. -11,9%; P less than 0,02) were seen in the Laerdal group. There was also a tendency towards improved oxygenation and lung compliance and quicker establishment of spontaneous respiration in the Laerdal group. We therefore conclude that the Laerdal resuscitator is superior to the Samson one in the management of infants with birth asphyxia.