T. Schmeiser

Streptococcal bacteremia in adult patients with leukemia undergoing aggressive chemotherapy. A review of 55 cases

SummaryWe reviewed 55 cases of streptococcal bacteremia in adult patients who received cytotoxic chemotherapy for treatment of acute leukemia. Viridans group streptococci were the most frequent species isolated (45 isolates). Hemolytic streptococci (four isolates), pneumococci (three isolates), and enterococci (three isolates) were infrequent. Clinical features of streptococcal bacteremia included fever, upper and lower respiratory infection, respiratory distress syndrome, soft tissue infection, and septic shock. Forty patients who had only streptococci, but no other organisms isolated from their blood, were compared with 36 cases of gram-negative bacillary bacteremia that occurred during the same study period within the same population at risk. The comparison showed that patients with streptococcal bacteremia had more often received high dose cytosine arabinoside as part of their chemotherapy (17 vs. five), had a longer mean duration of fever (11 vs. seven days, p<0.01) needed slightly more days of antibacterial therapy (15 vs. 12 days, p=0.07, not significant), and were more likely to have been treated with newer quinolones for infection prevention (30 vs. eight). No differences between both groups were found for age, underlying disease, remission status, duration of severe granulocytopenia, and number of superinfections. The overall mortality was 18% in streptococcal bacteremia and 17% in gram-negative bacillary bacteremia. Streptococci, especially viridans group streptococci, should now be regarded as frequent causes of serious life-threatening infections following aggressive chemotherapy in patients with hematologic malignancies.ZusammenfassungDie vorliegende Arbeit analysiert 55 Fälle von Streptokokken-Bakteriämie bei erwachsenen Patienten nach aggressiver antileukämischer Chemotherapie. Vergrünende Streptokokken waren die häufigsten Erreger (45 Isolate). Beta-hämolysierende Streptokokken (vier Isolate), Pneumokokken (drei Isolate) und Enterokokken (drei Isolate) waren dagegen eher selten. Klinisch waren die Infektionen gekennzeichnet durch Fieber, Beteiligung des oberen und unteren Respirationstrakts, Weichteilinfektion, durch Atemnotsyndrom und septischen Schock. 40 Patienten, bei denen ausschließlich Streptokokken in der Blutkultur nachgewiesen wurden, wurden verglichen mit 36 Patienten (ausgewählt nach denselben Kriterien) mit gramnegativer bakteriämischer Infektion. Die Gegenüberstellung ergab, daß Patienten mit Streptokokken-Bakteriämien häufiger hochdosiertes Cytosin-Arabinosid erhalten hatten (17 versus fünf Tage), eine längere Fieberdauer hatten (11 versus sieben Tage, P<0.01), etwas länger antibakterielle Therapie benötigten (15 versus zwölf Tage, P=0.07, nicht signifikant) und häufiger mit Fluorochinolonen zur Infektprophylaxe behandelt waren (30 versus acht). Beide Gruppen unterschieden sich nicht hinsichtlich Alter, Grunderkrankung, Dauer der Granulozytopenie und Häufigkeit von Superinfektionen. Die Letalität betrug 18% bei Streptokokken-Bakteriämie und 17% bei Gram-negativer Bakteriämie. Die Untersuchung zeigt, daß Streptokokken, besonders vergrünende Streptokokken, ungewöhnlich häufig unerwartet schwere Infektionen bei Patienten nach antileukämischer Chemotherapie verursachen können.

Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia

SummaryThe incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneicn=271, autologousn=27, syngeneicn=5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.

Antimicrobial prophylaxis in neutropenic patients after bone marrow transplantation.

SummaryFourty-one patients with haematological malignancies or severe aplastic anaemia underwent allogeneic or syngeneic bone marrow transplantation and received one of two forms of infection prophylaxis while granulocytopenic: total decontamination in strict reverse isolation (ITD, 26 patients) or selective decontamination of the digestive tract with barrier nursing (SD, 15 patients). The patients were evaluated for infection acquisition, fever days, days on systemic antibiotics and granulocyte transfusions from 48 hours after the beginning of the decontamination procedure until 1,000 granulocytes/µl have been reached. Ten of 26 patients of the ITD group remained free of febrile episodes and infections, whereas all patients of the SD group acquired infections (p < 0.001). During granulocytopenia patients of the ITD group had fewer fever days, were less frequently on systemic antibiotics and received fewer granulocyte transfusions as compared with the SD group. Both methods were obviously very effective in preventing gram-negative infections, infections caused byStaphylococcus aureus and infections due to yeasts or fungi. No death due to infection occurred in either group. However, the data of this study provide evidence that ITD is a more effective antimicrobial prophylaxis in bone marrow transplant recipients than SD.Zusammenfassung41 Patienten mit malignen hämatologischen Systemerkrankungen oder schwerer Panmyelopathie wurden mit einer allogenen oder syngenen Knochenmarktransplantation behandelt und erhielten zur Infektprophylaxe während der Phase der Granulozytopenie entweder eine totale Dekontamination in strikt reverser Isolation (ITD, 26 Patienten) oder eine selektive Dekontamination des Gastrointestinaltraktes mit „barrier nursing“ (SD, 15 Patienten). Die Patienten wurden ausgewertet bezüglich erworbener Infektionen, Fiebertagen, Tagen unter antibiotischer Therapie und dem Bedarf an Granulozytentransfusionen 48 Stunden nach Beginn der Dekontamination bis zum Erreichen von 1000 Granulozyten/µl. Zehn von 26 Patienten mit ITD blieben frei von Fieberepisoden und Infektionen, während alle Patienten mit SD Infektionen entwickelten (p < 0.001). Während der Phase der Granulozytopenie hatten Patienten der Gruppe ITD weniger Fiebertage, waren seltener unter systemischer Antibiotikatherapie und erhielten weniger häufig Granulozytentransfusionen im Vergleich zu Patienten der Gruppe SD. Beide Methoden waren sehr effektiv in der Prophylaxe gramnegativer Infektionen, Infektionen durchStaphylococcus aureus und Pilzinfektionen. In keiner Gruppe trat eine tödliche Infektion auf. Die Ergebnisse dieser Studie zeigen, daß mit ITD im Vergleich zu SD eine effizientere antimikrobielle Prophylaxe bei Patienten mit Knochenmarktransplantation möglich ist.

Thrombotic thrombocytopenic purpura in early pregnancy with maternal and fetal survival

SummaryThrombotic thrombocytopenic purpura (TTP) is a hematologic disorder which is clinically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic symptoms, and cardiac and renal involvement. The pathogenic mechanisms of this disease are poorly understood. It is well known that TTP is associated with pregnancy and that prognosis for the mother and child is poor. We present the first case of a severe TTP diagnosed in the first trimester of pregnancy (13th week of gestation) with maternal survival and birth of a healthy child which required continuous and intensive treatment with plasmatherapy until delivery. During a period of 24 weeks several attempts to discontinue plasma therapy failed because of continuous active disease, and it became evident that plasma infusions were not as effective as plasma exchanges. The fact that the patient entered into remission soon after delivery of a healthy child by cesarean section in the 37th gestational week shows that in this case pregnancy activated an unknown factor which does not cross the placenta and which can be removed by plasmapheresis.

Corynebacterium jeikeium bacteremia at a tertiary care center

SummaryDuring a six-year period 23 patients with isolation ofCorynebacterium jeikeium (formerly known asCorynebacterium group JK) from one or more blood cultures at a university hospital were identified. Cases occurred sporadically without time- or ward-related clustering. Review of the cases showed that most infections were nosocomial, that most of the patients had underlying malignant disease, had a chronic intravascular catheter implanted, had been pretreated with antibiotics, and were neutropenic at the time the blood cultures were drawn. Patients with only one versus those with more than one positive blood culture differed in some important aspects. Patients with only one positive blood culture were less likely to have acute leukemia, had significantly higher neutrophil counts and a shorter duration of preceding antibiotic treatment, and all had other probable causes of infection and fever. The mortality also appeared to be lower in these patients. Despite the possibility of increasing frequency of blood cultures positive forC. jeikeium, severe infections due to this organism continue to be largely confined to neutropenic patients with hematologic malignancy.ZusammenfassungIn einer Universitätsklinik wurde während eines Zeitraumes von sechs Jahren bei 23 PatientenCorynebacterium jeikeium aus Blutkulturen isoliert.C. jeikeium-Bakteriämien traten weder zeitlich noch örtlich gehäuft auf. Die retrospektive Analyse der Patientendaten zeigte, daß in den meisten Fällen eine maligne hämatologische Grunderkrankung mit Neutropenie vorlag, ein zentral-venöser Katheter implantiert und eine antibiotische Therapie vorausgegangen war. Die Patientenpopulation mit nur einer positiven Blutkultur unterschied sich in wichtigen Aspekten von derjenigen mit mehreren positiven Blutkulturen. So waren Patienten mit nur einer positiven Blutkultur seltener an akuter Leukämie erkrankt, hatten signifikant höhere neutrophile Granulozytenkonzentrationen im peripheren Blut und waren zuvor über einen kürzeren Zeitraum antibiotisch behandelt worden. Weiterhin fanden sich in dieser Patientengruppe in allen Fällen andere mögliche Ursachen der Fieberepisoden. Auch die Mortalität war deutlich geringer. Trotz des zunehmend häufigeren Nachweises vonCorynebacterium jeikeium in Blutkulturen bleiben schwere Infektionen durch diesen Erreger weiterhin meist auf die Patientenpopulation mit hämatologischer Grunderkrankung und Neutropenie beschränkt.

Infectious complications after allogeneic bone marrow transplantation with and without T-cell depletion of donor marrow.

SummaryThe infectious complications during different time intervals after allogeneic bone marrow transplantation (BMT) (day 0 to day 30, 31 to 100, 101 to 365, 366 to 730) were reviewed in 67 adult patients, 27 of whom received transplants without T-cell depletion (TCD) using methotrexate or cyclosporin A for prophylaxis of graft-versus-host disease (GvHD) and 40 of whom received donor marrow with TCD using the monoclonal anti-lymphocyte antibody campath-1 and human complement. The use of TCD reduced the incidence and severity of GvHD significantly (p<0.01), but was associated with an increased rate of graft rejections. During all time intervals patients with TCD had a similar, lower or statistically significantly lower number of bacterial, fungal or viral infections and a statistically significantly lower number of lethal infections (p=0.05) as compared with patients without TCD. This finding might be explained by the fact that with TCD immunological reconstitution can take place unimpaired by GvHD or its prophylaxis or treatment, resulting in a decreased incidence of infections.ZusammenfassungBei 67 erwachsenen Patienten wurden die Infektkomplikationen nach allogener Knochenmarktransplantation (KMT) während verschiedener Zeitintervalle (Tag 0 bis Tag 30, 31 bis 100, 101 bis 365, 366 bis 730) untersucht. Siebenundzwanzig Patienten erhielten ein Transplantat ohne T-Zell-Depletion (TCD) unter Verwendung von Methotrexat oder Cyclosporin A als Prophylaxe einer Graftversus-Host-Reaktion (GvHD) und 40 Patienten ein Transplantat mit TCD durch Einsatz des monoklonalen Lymphozyten-Antikörpers Campath-1 und humanem Komplement. Die TCD verminderte Häufigkeit und Schweregrad der GvHD signifikant (p<0.01), war aber mit einer erhöhten Transplantatabstoßung verknüpft. Während der verschiedenen Zeitintervalle hatten Patienten mit TCD eine ähnliche, niedrigere oder statistisch signifikant niedrigere Anzahl von bakteriellen, mykotischen oder viralen Infektionen und außerdem eine statistisch signifikant niedrigere Anzahl von tödlichen Infektionen (p=0.05) im Vergleich zu Patienten ohne TCD.

T-cell depletion versus methotrexate as GvHD-prophylaxis in allogeneic bone marrow transplantation for leukaemia

Graft‐versus‐host disease (GvHD) prophylaxis using methotrexate (23 patients) and T‐cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T‐cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD‐associated mortality from 79% to 5%. Actuarial disease‐free survival for low‐risk patients (57% with T‐cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T‐cell depletion. Prevention of graft failure after T cell‐depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.

Emerging Bacterial Pathogens in Patients with Acute Leukemia: Viridans Streptococci and Non-Fermentative Gram-Negative Bacilli

Several recent reports indicate that the spectrum of bacterial pathogens causing major infections in patients with acute leukemia may have substantially changed over the past years. This report reviews the epidemiology and clinical significance of viridans group streptococci and non-fermentative gramnegative bacilli (other than Pseudomonas aeruginosa) causing bloodstream infections in acute leukemia patients at our center.

Fluoroquinolones for Infection Prevention After Bone Marrow Transplantation

The major morbidity of bone marrow transplantation remains infection and graft versus host disease (GVHD). Bacterial infections have been particularly common early after transplantation when profound neutropenia largely characterizes the immunodeficiency of the recipients. Previous attempts to reduce the incidence of bacterial infections during this period have included the use of protected environments and the administration of nonabsorbable agents for enteric decontamination. In a more recent study we found that norfloxacin may be as effective as neomycin/polymyxin or trimethoprimsulfamethoxazole/ polymyxin in gastrointestinal “decontamination” and infection prevention in bone marrow transplant patients [1]. Given the higher in vitro antibacterial activity and more favourable pharmacokinetic properties of ofloxacin compared with norfloxacin, we subsequently performed an open study of ofloxacin prophylaxis in adult bone marrow transplant recipients.

Knochenmarktransplantation bei Panmyelopathie, akuter Leukämie und chronisch myeloischer Leukämie: Ergebnisse der „Ulmer Transplantationsgruppe“@@@Bone marrow transplantation for treatment of severe aplastic anaemia, acute leukaemia and chronic granulocytic leukaemia: Results of the “ulm bone marrow transplantation group“

SummaryFrom 1972–1983 53 patients underwent bone marrow transplantation. The median age was 18 years (3–41). 27 patients suffered from severe aplastic anaemia, 22 patients had acute leukaemia and 4 patients had chronic granulocytic leukaemia in chronic phase. Out of 22 patients with acute leukaemia, 2 had florid leukaemia, 2 had an early relapse and 18 patients were in first or second remission of their disease. 2/53 patients received a syngeneic transplant, 51/53 patients an allogeneic transplant. 47/51 patients had a HLA-A, B, C-identical, MLC-negative sibling donor, 1/51 had a HLA-A, B-C-identical, MLC-positive sibling donor, 2/51 a HLA-phaenotypical identical parental donor and 1/51 a HLA-identical, MLC-negative unrelated donor. The comparison of the results obtained in patients with severe aplastic anaemia transplanted from 1972–1979 with those transplanted from 1980–1983 shows that the bone marrow transplantation has to be performed in an early stage of the disease before the patients become multiple transfused, sensitized and severely infected and that the conditioning regimen for polytransfused patients has to be more intensive than in untransfused patients. From the patient group transplanted 1972–1979, only 1/14 patients is a long-term survivor in contrast to 8/13 patients transplanted from 1980–1983. 11/22 patients with acute leukaemia are alive between more than 5 years and 14 days after bone marrow transplantation. Only 1/4 patients, who were transplanted not in remission, is alive. For patients with acute leukaemia the bone marrow transplantation should be performed in an early stage of their disease when the tumor burden is small and when the patients are in good clinical condition. 2/4 patients with CGL are alive between 12 months and 3 months after bone marrow transplantation. In our patient group graft versus host disease was the most important problem with a high mortality due to GvHD associated infections.From 1972-1983 53 patients underwent bone marrow transplantation. The median age was 18 years (3-41). 27 patients suffered from severe aplastic anaemia, 22 patients had acute leukaemia and 4 patients had chronic granulocytic leukaemia in chronic phase. Out of 22 patients with acute leukaemia, 2 had florid leukaemia, 2 had an early relapse and 18 patients were in first or second remission of their disease. 2/53 patients received a syngeneic transplant, 51/53 patients an allogeneic transplant. 47/51 patients had a HLA-A, B, C-identical, MLC-negative sibling donor, 1/51 had a HLA-A, B-C-identical, MLC-positive sibling donor, 2/51 a HLA-phaenotypical identical parental donor and 1/51 a HLA-identical, MLC-negative unrelated donor. The comparison of the results obtained in patients with severe aplastic anaemia transplanted from 1972-1979 with those transplanted from 1980-1983 shows that the bone marrow transplantation has to be performed in an early stage of the disease before the patients become multiple transfused, sensitized and severely infected and that the conditioning regimen for polytransfused patients has to be more intensive than in untransfused patients. From the patient group transplanted 1972-1979, only 1/14 patients is a long-term survivor in contrast to 8/13 patients transplanted from 1980-1983. 11/22 patients with acute leukaemia are alive between more than 5 years and 14 days after bone marrow transplantation. Only 1/4 patients, who were transplanted not in remission, is alive.(ABSTRACT TRUNCATED AT 250 WORDS)