Eufronio G. Maderazo

Late Infections of Total Joint Prostheses: A Review and Recommendations for Prevention

The incidence of late infection of total joint prostheses is 0.6%. Because this incidence has increased from 0.08% in 1978, the authors reviewed their experience and the literature in search of pathogenetic and preventative measures. The most common pathogen responsible for late prosthetic joint infections was staphylococcus (54%; both Staphylococcus aureus and Staphylococcus epidermidis), even when infection was of dental origin. The three most common origins of infection were skin and soft tissue (46%), dental (15%), and urinary (13%). Escherichia coli was the most common pathogen when the source was the urinary tract. Mortality and cost calculations indicate that chemoprophylaxis is justified for dental procedures and probably also for other surgical procedures in organs containing microflora. Prophylaxis must include antistaphylococcal drugs. The first generation cephalosporin antibiotics are recommended.

Polymorphonuclear Leukocyte Adherence and Chemotaxis in Stressed and Healthy Neonates

ABSTRACT. Defects in polymorphonuclear neutrophil (PMN) adherence and chemotaxis in neonates are thought to be an important cause of their increased susceptibility to overwhelming bacterial infection. Few studies of these functions have been carried out in stressed neonates who are at even greater risk of infection. PMN adherence and chemotaxis were examined in 33 stressed neonates with acute lower respiratory illness, 13 healthy neonates, and 43 healthy adults using whole blood PMN adherence and chemotaxis assays. PMN chemotaxis was significantly decreased in stressed neonates (locomotion index of 38.4 ± 9.7 µm) compared with that of healthy neonates (48.9 ± 12.8 µm, p<0.01) or adults (61.6 ± 11.9 µm, p<0.001). PMN chemotaxis was studied during illness and recovery in 13 of the 33 stressed neonates and showed significant improvement during recovery (41.6 ± 9.9 and 53.2 ± 11.9 µm, respectively, p = 0.012). PMN adherence was decreased in stressed neonates (1.4 ± 1.6%) compared with that of adults (12.3 ± 11.4%, p<0.01) but was similar to that of healthy neonates (1.1 ± 1.4%). These findings suggest that further impairment of PMN chemotaxis in stressed neonates helps account for their increased susceptibility to overwhelming bacterial infection.

Leukotactic Dysfunction in Sarcoidosis

: The leukotactic function of patients with sarcoidosis was studied. A defect was found in 19 of the 20 patients tested and was due to moderately elevated serum levels of the chemotactic factor inactivator. The chemotactic factor inactivator levels were not as high as those previously reported in patients with Hodgkins disease or cirrhosis of the liver. The effect of the inactivator was irreversible and was directed toward all three of the chemotactic factors tested. The physicochemical characteristics of chemotactic factor inactivator in serum from sarcoid patients resembled in most respects the features of chemotactic factor inactivator in normal serum. As expected, the generation of chemotactic activity in some sarcoid serums by zymosan was impaired. The results of this study may relate to some of the reported defects in expression of immunity in sarcoid patients.

Serum-associated inhibition of leukotaxis in humans with cancer.

Abstract Human patients with a variety of malignant tumors have been studied to characterize the reported abnormality of leukotactic function. A majority of patients show a leukotactic defect that is serum associated and due to the presence of an inhibitor. This inhibitor impairs both neutrophil and monocyte reactivity to a variety of leukotactic factors. Phagocytic ability of leukocytes is also impaired by cancer serum and by the fractions of serum rich in the leukotactic inhibitor. The leukotactic inhibitor is cell directed in its function, is heat-stable and can be precipitated from serums with ammonium sulfate. Its sedimentation coefficient is biphasic, with values of approximately 7S and 10S. A similar or identical inhibitor is present in much lower concentration or activity in normal human serum. The presence in cancer serum of this leukotactic inhibitor may account for the well-known defects in the ability of cancer patients to express cellular inflammatory reactions.

Treatment of nocardial infection with trimethoprim and sulfamethoxazole

Abstract The development of a brain abscess due to Nocardia asteroides is described in a patient during therapy with ampicillin and either sulfadiazine or sulfisoxazole for pulmonary nocardiosis. Although the pulmonary nocardiosis responded to these antimicrobial agents, eradication of the cerebral nocardiosis required both surgical excision of the abscess and a 3 month course of trimethoprim (TMP)-sulfamethoxazole (SMX). It is speculated that the poor response of the cerebral infection to ampicillin and sulfisoxazole was related to their poor penetration into the cerebrospinal fluid. Four hours after both a 1 g intravenous dose of ampicillin and a 3 g oral dose of sulfisoxazole, there was no detectable activity of these drugs in the cerebrospinal fluid, despite adequate concentrations in the blood. On the other hand, 6 hours after a 160 mg oral dose of TMP, a level of 5.1 μg/g was detected in infected brain tissue. Synergistic activity between TMP and SMX was demonstrated: the minimum inhibitory concentration of TMP alone for the patients organism was greater than 5 μg/ml; of SMX alone, 24.5 μg/ml; for a 1:4 combination of TMP/SMX, 1.5 and 6.0 μg/ml, respectively; and for a 1:20 combination of TMP/ SMX, 0.5 and 9.5 μg/ml, respectively.

Micropore filter assay of human granulocyte locomotion: problems and solutions.

Abstract The problems encountered with the measurement of granulocyte migration by the micropore filter methods were discussed in detail. In evaluation by counting the number of cells that has reached a predetermined distance, the problems include: (i) the well-known errors created by cell detachment from the distal filter surface when the cells are allowed to completely penetrate the filter, (ii) the magnification or minification of results produced when incompletely migrated cell are disregarded, and (iii) problems in field selection and bias as a result of the nonuniform deposition of cells on the filter. When the distance migrated by the fastest-migrating cells is used (the “leading front technique”), the problems include: (i) nonusefulness in detecting abnormalities of mass migration and (ii) the potential problem of the faster-moving subpopulations not truly representing the migration characteristics of the total cell population, since two subpopulations of cells with distinct migration characteristics in micropore filters have been identified in human peripheral blood granulocytes. Consequently, a new method was developed to avoid these problems. This was accomplished by grading the cells according to their speed of migration, thus incorporating in the index the number of cells migrating and their distances of migration. This new method has been found to be reproducible and devoid of the above-mentioned problems.

Treatment of malakoplakia with trim trimethoprim-sulfamethoxazole

A case is described of malakoplakia involving the urinary tract and retroperitoneum with recalcitrant infection due to Escherichia coli which was not responsive to seemingly appropriate antibiotics and surgery for drainage, but which subsequently responded to treatment with trimethoprim-sulfamethoxazole. It is speculated that this drug combination may be helpful because of the ability of trimethoprim to enhance the killing of viable undigested microorganisms inside malakoplakic macrophages.

Effects of Intravenous Fat Infusion on Neonatal Neutrophil and Platelet Function

Intravenous fat (Intralipid) is used extensively as a major component of parenteral nutrition for patients in the neonatal intensive care unit. Abnormalities of polymorphonuclear leukocyte (PMN) and platelet number or function related to Intralipid infusion have been reported although conflicting results exist. In order to examine potential adverse hematologic effects of Intralipid, 10 ill neonates were studied before and after a 16-hr infusion of 1 g/kilo of Intralipid. PMN count, chemokinesis, chemotaxis, and aggregation were unchanged pre- and post intralipid infusion. Platelet count, bleeding time, and platelet aggregation were also unchanged. Similar results were obtained in vitro when neonatal and adult PMNs and platelets were incubated in Intralipid and their function analyzed. These findings suggest that short-term, low-dose Intralipid has no measurable impact on neonatal PMN or platelet activity and support its use in neonates even in the presence of infection or thrombocytopenia.

A randomized trial of replacement antioxidant vitamin therapy for neutrophil locomotory dysfunction in blunt trauma

Studies in patients with serious trauma indicate that the observed neutrophil (PMN) locomotory dysfunction is partly the result of auto-oxidation as shown by evidence of preactivation, diminished reducing capacity, and low serum and cellular ascorbic acid and alpha-tocopherol. To investigate whether replacement of the antioxidant vitamins ascorbic acid and alpha-tocopherol can improve the PMN locomotory defect, ascorbic acid, alpha-tocopherol, ascorbic acid and alpha-tocopherol, or placebo was administered to a total of 46 victims of blunt trauma. PMN locomotion was quantitated using a micropore filter assay. Locomotion data were analyzed by repeated measures analysis with a split plot design and data for days 2-6 after injury were compared. Compared with placebo, the antioxidants improved PMN locomotion. The mean differences in distance migrated (treated minus placebo) were ascorbic acid and alpha-tocopherol = 11.3 +/- 3.0 microns (one-tailed p = 0.001) (mean +/- SE); ascorbic acid = 4.7 +/- 3.4 microns (p = 0.19); and alpha-tocopherol = 3.3 +/- 2.9 microns (p = 0.27). Although both antioxidants given together produced the best results, a plot of the 95% confidence intervals indicates that ascorbic acid and alpha-tocopherol, either given alone, were also better than placebo. We conclude that antioxidant replacement therapy significantly improves the PMN locomotory abnormality in blunt trauma.

Additional evidence of autoxidation as a possible mechanism of neutrophil locomotory dysfunction in blunt trauma

Previous studies in victims of blunt injury suggest that the observed neutrophil (PMN) locomotory dysfunction is, in part, due to autoxidation. To further clarify the occurrence and significance of autoxidation, we studied changes in levels of glutathione in PMN and of ascorbic acid and a-tocopherol in serum and blood cells of postsurgical and blunt trauma patients. Levels of total, reduced, and oxidized glutathione in PMN from trauma patients were similar to normal controls. Serum and cellular ascorbic acid and α-tocopherol levels dropped significantly after injury and remained below normal control levels during the 7 to 8-day study period. Low serum α-tocopherol was partially explainable on the basis of changes in serum lipids. When serum samples of trauma patients were thawed unprotected without pyrogallol, there was significant loss of recoverable α-tocopherol, whereas no significant losses occurred with unprotected thawed normal sera. Less total reducing capacity was observed in PMN of trauma patients compared with normal controls. These findings indicate that synthesis and regeneration capacity of glutathione are intact but that the levels of the consumable antioxidants, ascorbic acid, and α-tocopherol are compromised after injury. These results add further support to the hypothesis that autoxidation occurs in trauma. (Crit Care Med 1990; 18:141)