Controversies in new antibiotic therapy for ambulatory patients

 The care of the febrile neutropenic patient has undergone a shift in the last 10 years with the realization that neutropenic patients presenting with fever do not constitute a homogeneous group. Strategies of risk assessment have allowed the testing of novel therapies including oupatient treatment with oral and intravenous antibiotics, either in combination regimens or as monotherapy; the addition of growth factors to hasten the return of the absolute neutrophil count; and the possibility of self-initiation of antibiotics by cancer patients when they develop fever. The clinical trials data regarding these new approaches will be reviewed, and areas requiring further research will be discussed.     

Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors.

Between 1972 and 1989, the incidence of viridans streptococcal bacteremia at the University of Texas M. D. Anderson Cancer Center in Houston increased from one case per 10,000 admissions to 47 cases per 10,000 admissions (P less than .0001). A shock syndrome characterized by hypotension, rash, palmar desquamation, adult respiratory distress syndrome, and occasionally death developed in 26% of cases of streptococcal septicemia but in only 4% of cases of septicemia involving other gram-positive bacteria (P = .0005). The risk of streptococcal infection increased with the prophylactic administration of trimethoprim-sulfamethoxazole or a fluoroquinolone (P less than .0001) and with profound neutropenia (P less than .0001). Treatment of chemotherapy-induced gastritis with antacids or with histamine type 2 (H2) antagonists was associated with a sevenfold increase in risk (P less than .001), while sucralfate therapy did not increase risk (P = .65). Streptococcal infection may result from gastric overgrowth of organisms resistant to trimethoprim-sulfamethoxazole in an antacid- or H2 antagonist-induced alkaline environment, with the gastrointestinal tract ulceration caused by antineoplastic therapy providing a convenient portal of entry. In patients receiving chemotherapy, replacement of antacids or H2 antagonists by an acid-sparing regimen should be considered to preserve the natural acidic barrier to infection.     

Stratification in clinical trials of febrile neutropenia

Patients with febrile neutropenia are characterized by well described prognostic factors leading to heterogeneity of risk of serious clinical outcomes. These prognostic factors complicate the design and interpretation of clinical trials of antimicrobial therapy in this population. Stratification is a method by which comparability of groups is ensured. This method can be employed prior to randomization or during the analysis. Factors that should be considered for stratification prior to randomization include the underlying neoplasm (leukemia vs solid tumor vs BMT), use of granulocyte growth factors, comorbid conditions and study site (in multicenter trials). In stratified analyses, trend in neutrophil count, site of infection, organism and susceptibility should be considered.     

The implementation of unit-based perinatal mortality audit in perinatal cooperation units in the northern region of the Netherlands

ABSTRACT: BACKGROUND: Perinatal (mortality) audit can be considered to be a way to improving the care for all pregnant women and their newborns by creating an opportunity to learn from unwanted events in the care process. In unit-based perinatal audit, the caregivers involved in cases that result in mortality are usually part of the audit group. This makes such an audit a delicate matter. METHODS: The purpose of this study was to implement unit-based perinatal mortality audit in all 15 perinatal cooperation units in the northern region of the Netherlands between September 2007 and March 2010. These units consist of hospital-based and independent community-based perinatal caregivers. The implementation strategy encompassed an information plan, an organization plan, and a training plan. The main outcomes are the number of participating perinatal cooperation units at the end of the project, the identified substandard factors (SSF), the actions to improve care, and the opinions of the participants. RESULTS: The perinatal mortality audit was implemented in all 15 perinatal cooperation units. 677 different caregivers analyzed 112 cases of perinatal mortality and identified 163 substandard factors. In 31 % of cases the guidelines were not followed and in 23 % care was not according to normal practice. In 28 % of cases, the documentation was not in order, while in 13 % of cases the communication between caregivers was insufficient. 442 actions to improve care were reported for 'external cooperation' (15 %), 'internal cooperation' (17 %), 'practice organization' (26 %), 'training and education' (10 %), and 'medical performance' (27 %). Valued aspects of the audit meetings were: the multidisciplinary character (13 %), the collective and non-judgmental search for substandard factors (21 %), the perception of safety (13 %), the motivation to reflect on one's own professional performance (5 %), and the inherent postgraduate education (10 %). CONCLUSION: Following our implementation strategy, the perinatal mortality audit has been successfully implemented in all 15 perinatal cooperation units. An important feature was our emphasis on the delicate character of the caregivers evaluating the care they provided. However, the actual implementation of the proposed actions for improving care is still a point of concern.     

Serratia bacteremia: review of 118 cases

A review was conducted of 118 episodes of serratia bacteremia in cancer patients during a 16-year period. The infection occurred most commonly in patients with acute leukemia. Most patients acquired the infection in the hospital, and 61% had received antibiotic therapy during the preceding 10 days. Fever occurred in 90% of cases and shock in 18%. Thirty-eight percent of patients had concomitant pneumonia. Patients with shock, pneumonia, or hemorrhage had a substantially poorer prognosis. The response rate was 75% for patients who received appropriate antibiotics, 22% for those who received inappropriate antibiotics, and 29% for those who received no antibiotics. Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor diagnosis. Patients who received only an aminoglycoside had the poorest response rate among those who received appropriate therapy.     

Similarity of secretory protein I from parathyroid gland to chromogranin A from adrenal medulla.

We have compared the amino acid and carbohydrate compositions, partial amino acid sequences, immunological crossreactivity, and physical properties of secretory protein I of the parathyroid gland and chromogranin A of adrenal gland. This comparison indicates that these proteins are similar molecules. Because secretory protein I is present in secretory granules containing parathormone and is cosecreted with the hormone, and because chromogranin A is contained within chromaffin granules and, likewise, is secreted with the catecholamines, the present observations raise the possibility that this class of protein plays a general role in hormone secretion or storage mechanisms.     

Circadian variation in serum amikacin levels

Variable serum amikacin levels have been reported in the same patient even after a steady state presumably has been reached. Therefore, the authors investigated the optimal schedule for monitoring serum levels of the drug in 50 neutropenic patients receiving continuous infusion amikacin therapy for infections. We found that levels obtained in the early morning hours were significantly higher than those obtained for the same patient in the evening. As these differences parallel those previously demonstrated for renal function, they may be explained by the pattern of drug clearance by the kidneys. We recommend that blood specimens for the detection of rising serum amikacin levels in a therapeutic setting be obtained in the early morning and at the same time each day so that meaningful comparisons of peak concentrations can be made. However, late evening samples should also be tested whenever dosage modifications are considered so that continuous therapeutic serum concentrations can be ensured.