Are first-generation cephalosporins obsolete? A retrospective, non-inferiority, cohort study comparing empirical therapy with cefazolin versus ceftriaxone for acute pyelonephritis in hospitalized patients.

OBJECTIVES: Literature is lacking regarding the utilization of first-generation cephalosporins for the treatment of acute pyelonephritis. The aim of this study was to determine whether cefazolin is non-inferior to ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. The primary outcome included a composite of symptomatic resolution plus either defervescence at 72 h or normalization of serum white blood cell count at 72 h (non-inferiority margin 15%). Secondary outcomes included length of stay and 30 day readmission. A subgroup analysis of the composite outcome was also conducted for imaging-confirmed pyelonephritis. METHODS: This was a retrospective, non-inferiority, multicentre, cohort study comparing cefazolin versus ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. RESULTS: Overall, 184 patients received one of the two treatments between July 2009 and March 2015. The composite outcome was achieved in 80/92 (87.0%) in the cefazolin group versus 79/92 (85.9%) in the ceftriaxone group (absolute difference 1.1%, 95% CI -11.1% to 8.9%, P = 0.83), meeting the pre-defined criteria for non-inferiority. The composite outcome for patients with imaging-confirmed pyelonephritis was achieved in 46/56 (82.1%) versus 42/50 (84.0%) for the cefazolin group and the ceftriaxone group, respectively (absolute difference 1.9%, 95% CI -12.8% to 16.5%, P = 0.80). Additionally, there were no statistically significant differences in length of stay or 30 day readmission for cystitis or pyelonephritis. CONCLUSIONS: Cefazolin was non-inferior to ceftriaxone with regard to clinical response for the treatment of hospitalized patients with acute pyelonephritis in this study. No difference was observed for length of stay or 30 day readmission.

HIV-1 proviral copy number in blood mononuclear cells from AIDS patients on zidovudine therapy.

The effect of treatment with 400-1,200 mg/day of zidovudine (ZDV) on HIV DNA concentrations in patient peripheral blood mononuclear cells (PBMCs) was studied in six patients during a 5- to 14-month period of therapy. HIV DNA was measured in PBMCs at intervals using a recently developed quantitative polymerase chain reaction assay. The amount of HIV DNA ranged from 2,000 to 40,000 copies of provirus per microgram of cellular DNA. The HIV provirus copy number showed little change with time in five patients, and increased and then remained constant in one patient. Thus, prolonged treatment with ZDV does not decrease the levels of HIV DNA in PBMCs.

Decreases in unintegrated HIV DNA are associated with antiretroviral therapy in AIDS patients.

Better markers are needed to monitor the efficacy of antiretroviral drugs in persons infected with human immunodeficiency virus (HIV). We investigated the effects of zidovudine (ZDV) and dideoxycytidine (ddC) on the presence of unintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from AIDS patients. DNA was extracted from PBMCs and separated into low molecular weight (unintegrated) and high molecular weight (integrated) chromosomal fractions. These DNA fractions were then amplified by a quantitative polymerase chain reaction (PCR) and the amount and percentage of unintegrated HIV DNA were determined. Very high levels of unintegrated HIV DNA were found in AIDS patients not receiving treatment with ZDV or ddC (median = 95% unintegrated HIV DNA). In contrast, most patients who had received 4 or more weeks of antiretroviral therapy had lower levels of unintegrated HIV DNA (median = 30% unintegrated HIV DNA for patients receiving ZDV). Paired samples taken from five patients before and after therapy showed a striking reduction in the percentage of unintegrated HIV DNA. The decrease in the proportion of unintegrated HIV DNA in AIDS patients was due to both a reduction in the copy number of unintegrated HIV DNA and an increase in the copy number of integrated HIV DNA. Thus, measurements of unintegrated and integrated HIV DNA may be useful in providing objective assessments of the effectiveness of antiretroviral therapies.

The effect of nifedipine alone or combined with low dose acetylsalicyclic acid on endotoxin-induced pulmonary hypertension in the piglet.

Cardiovascular responses to the calcium antagonist nifedipine, alone and combined with low dose acetylsalicyclic acid (ASA), were evaluated in a piglet model of endotoxin-induced pulmonary hypertension. All animals were anesthetized, paralyzed and mechanically ventilated. Cardiac output (CO), pulmonary artery pressure (PAP), aortic blood pressure (SAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAPM) and arterial blood gases were measured before and after induction of pulmonary hypertension by E. coli endotoxin and after treatment. Results of treated groups were compared to a control group of piglets subjected to the same dose (0.15 micrograms/kg i.v.) of endotoxin. Control animals responded to a bolus injection of endotoxin within 15 min with an increase in mean PAP by 110%. Pulmonary vascular resistance (PVR) increased by 144%. Mean arterial pressure did not change significantly from baseline values. In animals treated with a single dose of 1 mg/kg ASA prior to endotoxin, the initial pulmonary response was not quantitatively different from control values, whereas ASA 20 mg/kg abolished the pulmonary vascular reaction. The increase of systemic vascular resistance (SVR) produced by endotoxin was aggravated by high dose ASA. In piglets treated with nifedipine (4 micrograms/kg/min) over 30 min after the application of endotoxin with and without additional infusion of nifedipine 60 min prior to endotoxin the PVR could be attenuated. The combination of nifedipine and low dose ASA showed synergistic effects compared to control. The increase of mean PAP was significantly reduced, the PVR remained in baseline range due to a marked elevation of cardiac output.

Continuous measurement of cardiac output by the Fick principle in infants and children: comparison with the thermodilution method.

OBJECTIVE: To compare a system that continuously monitors cardiac output by the Fick principle with measurements by the thermodilution technique in pediatric patients. DESIGN: Prospective direct comparison of the above two techniques. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: 25 infants and children, aged 1 week to 17 years (median 10 months), who had undergone open heart surgery were studied. Only patients without an endotracheal tube leak and without a residual shunt were included. METHODS: The system based on the Fick principle uses measurements of oxygen consumption taken by a metabolic monitor and of arterial and mixed venous oxygen saturation taken by pulse- and fiberoptic oximetry to calculate cardiac output every 20s. INTERVENTIONS: In every patient one pair of measurements was taken. Continuous Fick and thermodilution cardiac output measurements were performed simultaneously, with the examiners remaining ignorant of the results of the other method. RESULTS: Cardiac output measurements ranged from 0.21 to 4.55 l/min. A good correlation coefficient was found: r2 = 0.98; P < 0.001; SEE = 0.41 l/min. The bias is absolute values and in percent of average cardiac output was - 0.05 l/min or - 4.4% with a precision of 0.32 l/min or 21.3% at 2 SD, respectively. The difference was most marked in a neonate with low cardiac output. CONCLUSION: Continuous measurement of cardiac output by the Fick principle offers a convenient method for the hemodynamic monitoring of unstable infants and children.

Continuous monitoring of mixed venous oxygen saturation in infants after cardiac surgery.

Continuous mixed venous oxygen saturation (SvO2c) was measured in 16 infants immediately after cardiac surgery. A polyurethane 4F, dual channel catheter (Opticath, Modell U440, Oximetrix) with fiberoptic filaments was introduced into the pulmonary artery during cardiothoracic surgery. The catheters were left in place for an average of 67.5 h (range 27 h -125 h) and there were no catheter-related complications. Correlation between continuous in vivo SvO2 values and in vitro values was satisfactory (r = 0.85), whereas a correlation between SvO2c and arterial oxygen saturation (SaO2) was not found (r = 0.07). The sampled arterial lactate values were inversely correlated to the simultaneously measured SvO2c, but the correlation coefficient was only r = -0.4. There was an inverse correlation between SvO2c and arteriovenous oxygen content difference (Ca-vDO2) (r = -0.82), and a marked inverse correlation to the calculated oxygen utilization ratio (r = -0.97). Therefore SvO2c continuously reflects the overall balance between oxygen consumption and delivery, but the use of SvO2 as a predictor of blood lactate levels is unreliable. A further purpose of the present study was to demonstrate the clinical applications and to show the usefulness of SvO2c-monitoring; particularly as a surveillance and early warning system, as a guide for assessing therapy and its relevance in interpreting other monitored parameters. In our opinion continuous SvO2 measurement is a reliable and valuable indicator of cardiopulmonary function in the immediate post-operative period, even in infants with complicated repair of cardiac malformations.

Successful treatment of a patient with ARDS after pneumonectomy using high-frequency oscillatory ventilation.

High frequency oscillatory ventilation (HFOV) was used in a patient who developed the acute respiratory distress syndrome 5 days following a right pneumonectomy for bronchogenic carcinoma. When conventional pressure-controlled ventilation failed to maintain adequate oxygenation, HFOV dramatically improved oxygenation within the first few hours of therapy. Pulmonary function and gas exchange recovered during a 10-day period of HFOV. No negative side effects were observed. Early use of HFOV may be a beneficial ventilation strategy for adults with acute pulmonary failure, even in the postoperative period after lung resection.

Reduced inotropic support after aprotinin therapy during pediatric cardiac operations.

BACKGROUND: Several reports indicate that aprotinin treatment before and during cardiopulmonary bypass (CPB) might have a protective effect on the myocardium. We evaluated the hemodynamic effects of perioperative aprotinin treatment. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 34 infants (mean age, 2.5 years) who had cardiac operations. Half of the patients received high-dose aprotinin therapy. There were no significant differences between the aprotinin and placebo groups with respect to age, weight, sex, aortic cross-clamp time, and CPB time. The following data were recorded at arrival in the intensive care unit 6, 12, 24, and 48 hours after termination of CPB: heart rate, blood pressure, left atrial pressure, central-peripheral temperature difference, arterial-central venous oxygen saturation difference, urine output, serum creatinine, lactate and neutrophil elastase levels, the Doppler echocardiographic factors shortening fraction and preejection period/left-ventricular ejection time, and cumulative doses of catecholamines (epinephrine), enoximone, and furosemide. RESULTS: No hemodynamic variable showed any significant difference between aprotinin and placebo groups. Urine output, creatinine, lactate, and elastase levels, as well as the cumulative doses of furosemide and epinephrine were not significantly different. Twelve hours after CPB 10 patients in the placebo group and 4 in the aprotinin group had received enoximone (p<0.05). The placebo group had received significantly larger doses of enoximone than the aprotinin group at arrival in the intensive care unit (0.13+/-0.05 versus 0 mg/kg), 12 hours after CPB (0.58+/-0.14 versus 0.18+/-0.09 mg/kg), 24 hours after CPB (1.11+/-0.24 versus 0.42+/-0.16 mg/kg), and 48 hours after CPB (1.61+/-0.40 versus 0.86+/-0.28). At 6 hours the difference did not reach statistical significance. CONCLUSIONS: Clinical and hemodynamic status of the aprotinin-treated patients was similar to that of the placebo-treated patients in the first 48 hours after CPB. The placebo group, however, required significantly more inotropic support by enoximone than the aprotinin group to achieve this goal.

Evaluation of gastric intramucosal pH during and after pediatric cardiac surgery.

OBJECTIVES: In adult patients, intramucosal pH (pHi) has been advocated to detect postoperative complications. The purpose of our study was to evaluate this technique in pediatric patients during and after cardiac surgery. METHODS: Thirty-five infants (age: 5 days to 15 years, median 1.8 years; and weight: 3.2-32 kg, median 9.8 kg) were studied. pHi was measured before cardiopulmonary bypass (CPB), after 30 min of CPB, prior to weaning off CPB, at intensive care unit arrival, and 6, 12, 24, 48 and 72 h after surgery. RESULTS: There were no complications related to the tonometer. A pathologically low pHi < 7.32 was found during surgery in less than 17%, at intensive care unit arrival in 83% and after 48 h in 18%. pHi values were lower (P < 0.05) at intensive care unit arrival (7.25 +/- 0.08) and after 6 h (7.28 +/- 0.09) than afterwards. pHi correlated with arterial pH (r = 0.66), central-peripheral temperature difference (r = -0.36), lactate (r = -0.32) and central venous pressure (r = -0.21). Patients after a Fontan procedure had postoperatively a lower pHi than after other operations (P < 0.05). None of the patients died or developed organ failure. Six patients had signs of organ dysfunction. Their pHi (median 7.23, range 7.14-7.28) could not differentiate them from the other patients. CONCLUSIONS: With current equipment, tonometry cannot be recommended for the management of pediatric patients after cardiac surgery. However, as a semi-invasive method tonometry deserves further evaluation.

Norepinephrine, enoximone, and nitric oxide for treatment of myocardial stunning and pulmonary hypertension in a newborn with diaphragmatic hernia.

A newborn with right diaphragmatic hernia suffered myocardial stunning and suprasystemic pulmonary hypertension secondary to postpartal asphyxia. In addition to conventional therapy, norepinephrine, enoximone, and inhalational nitric oxide were successfully used. Norepinephrine improved myocardial perfusion pressure; the addition of enoximone, a phosphodiesterase-inhibitor, to beta-adrenergic agents increased cardiac performance. with decreasing concentrations of inhalational nitric oxide, severe pulmonary hypertension resolved after a few days, suggesting that transient endothelial dysfunction was partially responsible for pulmonary vasoconstriction in the newborn with congenital diaphragmatic hernia.

Identification of a novel compound heterozygote SCO2 mutation in cytochrome c oxidase deficient fatal infantile cardioencephalomyopathy.

UNLABELLED: Fatal infantile cardioencephalomyopathy (OMIM No. 604377) is a disorder of the mitochondrial respiratory chain and is characterised by neonatal progressive muscular hypotonia and cardiomyopathy because of severe Cytochrome c oxidase deficiency. Here we report a novel mutation in the Cytochrome c oxidase assembly gene SCO2 in an infant with fatal infantile cardioencephalomyopathy despite normal initial metabolic screening. CONCLUSION: In newborns with unexplained muscular hypotonia and cardiomyopathy genetic testing of mitochondrial respiratory chain disorders might be helpful to establish a final diagnosis and guide treatment decisions.

[Preparation of a compatibility chart for intravenous drug therapy in neonatal and pediatric intensive care units]. / Erstellung einer Kompatibilitätstabelle für die intravenöse Pharmakotherapie auf neonatologischen und pädiatrischen Intensivstationen.

BACKGROUND: Modern neonatal and pediatric intensive care includes a sophisticated pharmacotherapy with numerous drugs, mainly administered intravenously. Often, despite the use of multi-lumen central venous lines, more peripheral venous accesses are required. To reduce the necessity of numerous venous lines on one hand and on the other hand to avoid complications from incompatibilities of the administered drugs, we compiled a compatibility chart, encompassing more substances than covered in previously available charts. METHODS: Information on compatibility of commonly prescribed drugs was collected by analysis of manufacturers' information, medical and pharmaceutical handbooks, and a literature research. RESULTS: Available data on compatibility of 78 drugs were displayed in a two-dimensional chart. Beside the pH of each drug, compatibility of drug combinations was encoded for simultaneous infusion. Special emphasis was on security of the therapy. CONCLUSION: The compatibility chart gives quick reference for Data on compatibility of intravenously administered drugs in neonatal and pediatric intensive care.

Testicular abscess caused by Salmonella typhi.

This case, which we believe is the first report of a bacteriologically proven infection of the testis by Salmonella typhi, illustrates the occurrence of this complication in the convalescent phase of typhoid fever and the absence of a clinically evident preceding bacteremic phase. The case also emphasizes the need for prolonged antibiotic therapy and the role of surgery in treatment of relapses.

Effects of dobutamine on left ventricular performance in newborns as determined by systolic time intervals.

To evaluate the effects of dobutamine on myocardial function in newborns, left ventricular systolic time intervals (STI) - normalized pre-ejection period (PEPI), normalized left ventricular ejection time (LVETI) and pre-ejection period to left ventricular ejection time ratio (PEP/LVET) - were assessed by echocardiography in 18 newborns treated with dobutamine for clinically diagnosed heart failure. Examinations were performed prior to and 30 min after starting dobutamine infusion (7.5 or 10 micrograms/kg per min). Patients were assigned to two groups according to their PEP/LVET prior to dobutamine administration: group I (n = 9) with pre-treatment PEP/LVET less than or equal to 0.35 and group II (n = 9) with pre-treatment PEP/LVET greater than 0.35. While there was no change of STI in group I, dobutamine infusion resulted in a significant decrease in PEPI (from 102 +/- 4.8 to 87.8 +/- 4.2; mean +/- SEM; P less than 0.01) and of PEP/LVET (from 0.56 +/- 0.05 to 0.45 +/- 0.05; mean +/- SEM; P less than 0.01) and in a significant increase of LVETI (from 237.6 +/- 5.6 to 253.3 +/- 5.2; mean +/- SEM; P less than 0.01) in group II. Heart rate increased significantly in both groups. Left ventricular end-diastolic dimension, also assessed by echocardiography, did not change in the eight studies performed. An increase in mean arterial pressure was found in three out of five newborns of group II and in one out of four patients in group I. It is concluded that dobutamine can improve cardiac performance in newborns with impaired left ventricular function. This effect is probably due to an improvement in myocardial contractility.

Evaluation of the pulse wave arrival time as a marker for blood pressure changes in critically ill infants and children.

OBJECTIVE: Pulse arrival time (PAT), which is the interval between the R wave of the electrocardiogram (ECG) and the arrival of the pulse wave peripherally, has been reported to be suitable for use as an indirect measure of blood pressure change. The purpose of this study was to evaluate, in critically ill infants and children, the degree to which 1/PAT covaries with systolic, diastolic, and mean blood pressure, as well as heart rate. METHODS: A laboratory device was used to calculate PAT in real time from the ECG and the plethysmographic curve of pulse oximetry used for routine monitoring. Calculated PAT and corresponding blood pressures and heart rate were stored on hard disk. A total of 15 critically ill patients, aged 6 days to 16 years, weighing 3 to 80 kg, were studied. RESULTS: In all patients, one period of 11,000 to 36,000 beats could be evaluated. Mean correlation coefficients were best for systolic blood pressure (r = 0.73), followed by mean blood pressure (r = 0.68) and diastolic blood pressure (r = 0.61), and, finally, heart rate (r = 0.52). In 7 patients, the correlation coefficient for systolic blood pressure was > 0.9; but, in 4 patients, it was < 0.5. CONCLUSIONS: We conclude that the correlation between 1/PAT and systolic blood pressure is not strong enough to serve as a marker for blood pressure changes in critically ill infants and children. This may be due to changes of the preejection period, which is part of the PAT.

Independent right lung high frequency and left lung conventional ventilation in the management of severe air leak during ARDS.

Pulmonary air leaks are one of the most common problems in patients with the adult respiratory distress syndrome, ARDS. We report what we believe to be the first case in which unilateral high-frequency ventilation combined with contralateral conventional positive pressure ventilation has been used successfully to manage severe air leak in an infant with ARDS.

[Linezolid in two premature babies with necrotizing enterocolitis and infection with vancomycin-resistant enterococcus]. / Linezolidtherapie bei zwei Frühgeborenen mit nekrotisierender Enterokolitis und Infektion durch Vancomycin-resistente Enterokokken.

The use of the antibiotic Linezolid in two premature babies with necrotizing enterocolitis and infection with vancomycin-resistant enterococcus is described. Therapy with Linezolid in cause of necrotizing enterocolitis is an exception. Actually there are no proven recommendations for the use in this age group. Despite the successfully results more investigations for the use of linezolid in newborns and prematures are necessary.

Evaluation of the valve area underestimation by the continuity equation.

During the last years, noninvasive determination of the aortic valve area by Doppler echocardiography using the continuity equation became popular. However, a systematic valve area underestimation of about 15% compared to invasive measurements using the Gorlin formula has been reported. The cause therefore is unknown. The purpose of this study was to evaluate whether the valve area underestimation by the Doppler method might be due to differences in the hydrodynamic background of both methods. This comparison is facilitated by the fact that the Gorlin formula is based on the continuity equation. Compared to the continuity equation, there are four changes within the Gorlin formula: (1) the additional use of a discharge coefficient, which leads to valve area overestimation by the factor 1.17; (2) neglect of the pre-stenotic velocity, causing further overestimation by the factor 1.036 (in mild stenosis this factor may be 1.18 and more); (3) the wrong calculation of the mean pressure drop, which leads to a mean change by the factor 0.95, and (4) the incorrect substitution of the height by the pressure drop in the derivation of the Gorlin formula causes underestimation by the factor 0.97. Combining these four factors results in valve area overestimation of the Gorlin formula compared to the continuity equation by the factor 1.12. This explains to a large extent the valve area underestimation by the continuity equation.