Thrombocytosis under ciprofloxacin and tazobactam/piperacillin

Whether the simultaneous administration of ciprofloxacin or tazobactam/piperacillin increases the risk of thrombocytosis is unknown. Broncho-pulmonary infection in a 50-year-old male with acute, hypertensive, intracerebral bleeding, necessitated therapy with cefpirome (2 g/day, 6 days), ciprofloxacin (800 mg/d, 11 days) and tazobactam/piperacillin (9 g/day, 11 days). Starting with the 8th hospital day, the thrombocyte count steadily increased from 410000/microl to a maximum of 1132000/microl on hospital day 16. Afterwards the thrombocyte count continuously decreased to normal values. Primary thrombocytosis and secondary causes were excluded. Since the thrombocyte count started to increase immediately after initiation and dropped immediately after discontinuation of ciprofloxacin and tazobactam/piperacillin and all other drugs were discontinued already before or were started after the nadir of the thrombocyte count, these two antibiotics were regarded causative. It is concluded that simultaneous administration of ciprofloxacin and tazobactam/piperacillin may cause marked thrombocytosis. Discontinuation of these two antibiotics results in an immediate decline of the thrombocyte count to normal values within three weeks.     

Leukocytopenia, Thrombocytopenia and Fever Related to Piperacillin/Tazobactam Treatment – A Retrospective Analysis in 38 Children with Cytic Fibrosis

Summary Bone marrow suppression is an important adverse reaction to most betalactam antibiotics. Recently it was suggested that piperacillin/tazobactam (PT) also may cause bone marrow toxicity. We retrospectively analyzed 100 IV antibiotic treatment courses (mean duration 12.5 days) in 38 patients (median age 14 years) with cystic fibrosis (CF) who were treated in our hospital. Of the patients receiving PT (84%), 6 patients (18.75% of PT-treated patients, 10.3% of PT treatment courses) developed fever, malaise and headache during treatment without signs of acute infection. In one patient definite thrombocytopenia and neutropenia, in two others a milder decrease in leukocyte and thrombocyte counts was observed after the onset of fever. The events were time- and dose-dependent occurring between day 11 and 15 of treatment. Treatment courses lasted longer (14.2 vs 11.3 days; p < 0.05) and patients had received a higher cumulative dose of PT (4919 ± 1975 mg/kg b.w. vs 3161 ± 1635 mg/kg; p < 0.02, Student's t-test) in the affected group than in the unaffected group. After discontinuation of PT, fever subsided within 24 h and blood cell counts normalized. We hypothesize that these fever episodes and changes of blood parameters are related to PT therapy. Received: February 8, 1999 · Accepted: September 17, 1999     

Drug Fever Induced by Piperacillin/Tazobactam in a Scoliosis Patient: A Case Report

Drug fever is frequently underrecognized by clinicians despite its common occurrence. Fever induced by piperacillin/tazobactam has not been reported in scoliosis correction surgery.Drug fever caused by piperacillin/tazobactam in a scoliosis patient was described.A 36-year-old woman with adult scoliosis undergoing correction surgery was reported. She developed a fever after an intake of piperacillin/tazobactam for 3 days. Eosinophil count, erythrocyte sedimentation rate, and C-reactive proteins were increased in her blood examination. Thorough history, chest radiography, blood cultures, physical examination, and urinalysis revealed no evidences of fever. A drug fever is therefore considered. The fever lasted for 2 weeks and her body temperature come back to normal 4 days after piperacillin/tazobactam cessation.Fever could be caused by piperacillin/tazobactam. The drug fever''s diagnosis is easily confounded by a co-occurring infection. Therefore, it is crucial for clinicians to doubt drugs as a reason when no other origin of fever could be identified in a patient.     

Intermittent melphalan in the treatment of essential thrombocytosis with haemorrhage or thrombosis

178 episodes of essential thrombocytosis with symptoms of haemorrhage or thrombosis, were treated in 15 patients with melphalan (5 mg/m2 orally during 4 d). An average reduction in the platelet count of 77% was achieved by oral melphalan in 14 responding patients. 1 patient appeared to be refractory to oral therapy, but a decrease of the thrombocyte count was achieved after intravenous administration of melphalan. All responding patients experienced a relief of the thrombocytosis-associated clinical symptoms. Reduction of the thrombocyte count persisted for 3-4 wk.     

外科感染铜绿假单胞菌的耐药性分析

目的：探讨基层医院外科感染铜绿假单胞菌（PAE）对常用抗菌药物的耐药性,为临床合理使用抗生素提供实验依据。方法：从外科感染性标本中分离的179株PAE培养鉴定严格按照《全国临床检验操作规程》进行,采用KB法对PAE进行14种常用抗菌药物的药敏试验。结果：PAE对常用抗菌药物的药敏试验结果表明：PAE对碳青霉烯类抗生素亚胺培南和美罗培南敏感率最高,均为97.8%;其次,对头孢哌酮/舒巴坦、哌拉西林/他唑巴坦、阿米卡星等敏感率较高,分别为87.7%、84.4%、80.4%;而对氨曲南、头孢噻肟、环丙沙星、左氧氟沙星耐药率很高,均〉50%。结论：我院外科医院感染铜绿假单胞菌具有多药耐药性,必须加强监测与控制。     

The effects of 5-fluorouracil on hematopoiesis: studies of murine megakaryocyte-CFC, granulocyte-macrophage-CFC, and peripheral blood cell levels

the effect of 5-fluorouracil (5-FU) on megakaryocytopoiesis in mice was studied with assays of megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen and simultaneous determinations of peripheral blood counts, after a single intraperitoneal dose (150 mg/kg) of 5-FU. Although only moderate thrombocytopenia (platelet count 40% of control values) occurred at 7 days following administration of 5-FU, sustained rebound thrombocytosis (platelets 200-250% of control values) was observed from days 11 to 17. No rebound leukocytosis was detected despite comparable initial leukopenia. Megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen were decreased for 2 and 5 days, respectively, after administration of 5-FU. Subsequently, there was a prolonged rebound increase in the total number of Meg-CFC in the spleen from days 11 to 17 after 5-FU, a phenomenon which did not occur with Meg-CFC derived from the bone marrow. Granulocyte-macrophage colony-forming cells (GM-CFC) in bone marrow and spleen exhibited alterations which were similar to those of Meg-CFC, indicating similar sensitivities of GM-CFC and Meg-CFC to 5-FU. Normal feedback mechanisms which control platelet levels are perturbed for almost 3 wk after administration of 5-FU. The simultaneous occurrence of maximal thrombocytosis and increased splenic Meg-CFC suggests that increased platelet production after 5-FU is associated with concomitant stimulation of the megakaryocyte progenitor compartment in the mouse spleen. However, the concurrence of thrombocytosis and increased splenic Meg-CFC indicates that elevated levels of Meg-CFC did not initiate the period of thrombocytosis.     

Extremely Elevated Procalcitonin in a Case of Acetaminophen Overdose and Acute Liver Injury

We herein report a 46-year-old man who suffered an intentional acetaminophen overdose. Laboratory results revealed leukocytosis and an elevated procalcitonin level (8.48 ng/mL). Computed tomography showed findings suggesting possible colitis. Due to concerns about sepsis in addition to acetaminophen overdose, oral N-acetyl cysteine and piperacillin/tazobactam were started. His procalcitonin levels further increased; however, the patient remained afebrile, and the C-reactive protein levels were normal. Piperacillin/tazobactam was discontinued, and he remained stable without antibiotics. The present case shows that the toxicokinetics of acetaminophen overdose can cause an elevated procalcitonin level. Furthermore, procalcitonin levels alone should not guide the need for antibiotics in such cases.     

An adult patient with varicella preceded by acute thrombocytopenia]

A 40-year-old man was admitted to our hospital because of a tendency to bleed. A diagnosis of idiopathic thrombocytopenic purpura was made, and oral prednisolone (1 mg/kg/day) was administered immediately. Three days after admission, hemorrhagic skin rashes highly suggestive of varicella appeared. The oral prednisolone was discontinued, and intravenous gamma-globulin (400 mg/kg/day for 3 days) and aciclovir (750 mg/day for 7 days) were started. The platelet count increased to 254,000/microliter over the next five days, and the skin rashes associated with varicella subsided within a week. We suggest that, in a minority of patients with varicella zoster infection, thrombocytopenia can precede the typical skin rashes, so a search for possible underlying viral infection should be made, and if necessary, immediate treatment started.     

新生儿铜绿假单胞菌耐药性分析

目的：了解新生儿患者临床分离的铜绿假单胞菌耐药情况。方法：采用API细菌鉴定分析系统对2004—2008年湖北省妇幼保健院新生儿住院患者临床分离细菌进行鉴定,并采用Kirby-Bauer法选用13种常用抗菌药物进行体外药物敏感试验。结果：354株铜绿假单胞菌主要来源于痰和胃液标本,共占74.6%;其在临床病区分布中以重症监护病房为主,占81.9%。354株铜绿假单胞菌对环丙沙星、阿米卡星、头孢他啶、头孢吡肟、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、亚胺培南和美罗培南的敏感率较高,均〉80%;而对哌拉西林、美洛西林、头孢噻肟、头孢哌酮、氨曲南的敏感率则次之。354株铜绿假单胞菌中多重耐药菌占25.7%,且有逐年增多的趋势。结论：铜绿假单胞菌是引起新生儿医院感染的最常见病原菌之一,对抗菌药物呈多重耐药,临床治疗应结合新生儿患者的特点合理选用抗菌药物,以减少耐药株的出现与扩散。     

Acute promyelocytic leukemia accompanied by retinoic acid syndrome with complications of acute myocardial infarction and cerebral infarction during treatment with all-trans retinoic acid

A 71-year-old man visited our hospital complaining of fever and a bleeding tendency. The peripheral blood WBC count was 10,400/microliter with 90% promyelocytes. The bone marrow was hypercellular with 88% promyelocytes. Disseminated intravascular coagulation was recognized. The patient was diagnosed as having acute promyelocytic leukemia and was treated with daily oral administration of all-trans retionic acid (ATRA) (45 mg/m2/day) and cytarabine (160 mg/day, intravenous drip infusion for the initial five days). The ATRA treatment induced leukemic cells to undergo mature myeloid differentiation. On day 24 after the start of treatment, the WBC count rapidly increased and acute myocardial infarction appeared, with consciousness disturbance and bilateral Babinski reflex appearing three hours later. Magnetic resonance imaging showed a fresh lacunar infarction of the right lenticular nucleus, and serum levels of IL-6 and PAI-1 were found to be elevated at the onset of infarction. Since there was a possibility that the retinoic acid syndrome (RAS) might have helped bring about the infarctions, we stopped the ATRA treatment and started administration of methyl-prednisolone (500 mg/body/day for 3 days) and gabexate mesilate. The WBC count decreased immediately and the consciousness disturbance improved. In this case, ATRA treatment might have initiated the RAS and resulted in some endothelial damage, thus causing the infarctions.     

Original Article: Changes in Platelet Function, von Willebrand Factor and Factor VIII in Patients Undergoing Aorto-bifemoral By-pass with Dacron Grafts

Platelets play a major role in the development of patency complications in vascular grafts. The aim of this study was to evaluate changes in platelet count and function, and also in factor VIII:C (FVIII:C) and von Willebrand factor (vWF) plasma levels, induced by aorto-bifemoral by-pass with Dacron grafts in seven patients. Platelet count, platelet aggregate ratio (PAR), and platelet aggregability induced by several stimuli, as well as FVIII:C and vWF plasma levels were evaluated before and on days 1,4,9 and 11 after surgery. We observed a mild thrombocytopenia on day 1, followed by a progressive increase in platelet count, which attained a relative thrombocytosis on the 11th day. PAR did not vary significantly during the whole observation period. Platelet aggregation, assayed by the optical method using ADP, epinephrine, arachidonic acid, collagen and ristocetin, (decreased on days 1 and 4). Thereafter, an increase in aggregation was observed until day 11 when hyperaggregability was verified. FVIII:C and vWF peaked on the 4th day, decreasing progressively to pre-surgery values on day 11.     

Original Article: Changes in Platelet Function,von Willebrand Factor and Factor VIII in Patients Undergoing Aorto-bifemoral By-pass with Dacron Grafts

Platelets play a major role in the development of patency complications in vascular grafts. The aim of this study was to evaluate changes in platelet count and function, and also in factor VIII:C (FVIII:C) and von Willebrand factor (vWF) plasma levels, induced by aorto-bifemoral by-pass with Dacron grafts in seven patients. Platelet count, platelet aggregate ratio (PAR), and platelet aggregability induced by several stimuli, as well as FVIII:C and vWF plasma levels were evaluated before and on days 1,4,9 and 11 after surgery. We observed a mild thrombocytopenia on day 1, followed by a progressive increase in platelet count, which attained a relative thrombocytosis on the 11th day. PAR did not vary significantly during the whole observation period. Platelet aggregation, assayed by the optical method using ADP, epinephrine, arachidonic acid, collagen and ristocetin, (decreased on days 1 and 4). Thereafter, an increase in aggregation was observed until day 11 when hyperaggregability was verified. FVIII:C and vWF peaked on the 4th day, decreasing progressively to pre-surgery values on day 11.     

Lenograstim after autologous peripheral blood progenitor cell transplantation: results of a double-blind, randomized trial

A phase III, randomized, double-blind, placebo-controlled, multi-center trial was conducted in order to compare the incidence of microbiologically defined infections occurring after high-dose chemotherapy (HDT) and ASCT in 98 patients given lenograstim (Granocyte) and 94 patients given placebo after transplantation. Hematopoietic recovery, the use of i.v. antibiotics, the numbers of red blood cell and platelet transfusions, the days spent in hospital, and the days on parenteral nutrition were also compared. The incidence of infections until neutrophil recovery was significantly less in patients who received lenograstim after HDT and ASCT as compared to patients who received placebo (66 of 98 vs 86 of 94 patients, P<0.001). Lenograstim also significantly reduced the use of i.v. antibiotics (P<0.001) and the median duration of i.v. antibiotic treatment (8 days vs 10 days, P=0.04), improved neutrophil recovery (absolute neutrophil count >0.5 x 10(9)/l: 11 days vs 15 days, P<0.001) and reduced the number of days spent in hospital (15 days vs 17 days, P<0.001). The administration of lenograstim after HDT and ASCT significantly reduces the incidence of microbiologically defined infections until neutrophil recovery. It also leads to less use of antibiotics and earlier discharge from hospital.     

Optimal timing of granulocyte colony-stimulating factor (G-CSF) administration after bone marrow transplantation

The positive role of G-CSF in hastening the myeloid recovery of patients undergoing allogeneic bone marrow transplantation (ALLO-BMT) or autologous bone marrow transplantation (ABMT) has recently been established. Considerable knowledge about adequate doses and route of administration has been accumulated in the past few years. Nonetheless, the optimal time to start growth-factor administration remains undetermined. We have performed a stratified study according to the source of hematopoietic progenitors (ALLO-BMT or ABMT), underlying disease and its stage, and acute graft-versus-host disease (GVHD) prophylaxis regimen and randomized patients in two arms: group A, which started G-CSF on day 0 (36 patients), and group B, which started on day +7 post-BMT (39 patients). The same dose (5 Μg/kg/day) and route of administration were employed in both groups. We found no significant differences in the time to reach an absolute neutrophil count (ANC) of 0.1, 0.5, and 1×10⁹/l and 50×10⁹ platelets/l (medians: 10 and 11, 14.5 and 14, 17 and 16, 23 and 24 days, respectively, in groups A and B). We did not find differences in the days of fever or days on antibiotic treatment with less than 1×10⁹/l ANC, rate of bacteriemia, or days of hospitalization in both groups. In contrast, a considerable saving of GCSF in B group was found (mean days of infusion in group A, 18, versus 11 in group B) (p<0.0001). This is equivalent to a saving of 1120 $US per patient. Therefore, early use of G-CSF after BMT is useless and more expensive and provides no advantage over delayed administration.     

老年下呼吸道感染患者肺炎克雷伯菌和大肠埃希菌耐药性分析

目的：监测老年下呼吸道感染患者肺炎克雷伯菌和大肠埃希菌的耐药性。为临床合理应用抗生素提供依据。方法：对我院下呼吸道感染患者中分离出的肺炎克雷伯菌和大肠埃希菌240株，以Kirby-Bauer(K-B)琼脂扩散法作药敏试验；以美国临床实验室标准委员会（NCCLS）1999年推荐的表型确认试验检测超广谱β－内酰胺酶（ESBLs）。结果：老年组和非老年组肺炎克雷伯菌和大肠埃希菌对14例抗生素的耐药率分别为阿莫西林93．2％和87．3％，哌拉西林57．1％和42．9％、头孢呋新51．4％和33．3％、头孢噻肟40．1％和17．5％、头孢他啶13．6％和3．2％、头孢曲松39．0％和17．5％、头孢哌酮37．3％和15．9％，头孢吡肟10．2％和3．2％、阿米卡星47．5％和34．9％，环丙沙星54．2％和38．1％、亚胺培南15．9％、头孢吡肟10．2％和3．2％、阿米卡星47．5％和34．9％、环丙沙星54．2％和38．1％，亚胺培南0和0、头孢哌酮／舒巴坦0和0、哌拉西林／三唑巴坦1．1％和0、头孢美唑9．6％和4．8％。78株肺炎克雷伯菌和大肠埃希菌被证实为产ESBLs菌，ESBLs检测出率为32．5％（78／240），其中老年组ESBLs检出率为38．4％（68／177），非老年组ESBLs检出率为15．9％（10／63）。亚胺培南，头孢哌酮／舒巴坦，哌拉西林／三唑巴坦和头孢美唑对产ESBLs菌的耐药率最低，分别为0、0、2．6％和12．8％。结论：老年下呼吸道感染患者肺炎克雷伯菌和大肠埃希菌的耐药率和ESBLs检出率均显著高于非老年患者；亚胺培南，头孢哌酮／舒巴坦、哌拉西林／三唑巴坦和头孢美唑是治疗由产ESBLs菌引起感染的有效抗生素。     

Comparative activity of cefepime with several antimicrobials against aerobic Gram-negative and Gram-positive organisms isolated from patients across Canada in 1993

To compare the activity of cefepime, a fourth-generation cephalosporin, with several available antimicrobials, in vitro susceptibility studies were carried out on bacteria commonly associated with various infections, including sepsis. Ten tertiary care hospital laboratories in six provinces provided 1276 clinically relevant isolates of aerobic Gram-negative bacilli and Gram-positive cocci during 1993. When the activity of each of the antimicrobials was determined against all isolates submitted, cefepime, piperacillin/tazobactam, imipenem and ciprofloxacin all had minimal inhibitory concentrations for 90% of the organisms (mic(90)) two or more dilutions below the mic resistant category. Gentamicin's mic(90) against all organisms tested was one dilution below the mic resistant category. The mic(90)s of the third-generation cephalosporins, piperacillin and ticarcillin/clavulanate, for Enterobacter species fell in the resistant category. This is presumably due to constitutive high level chromosomal cephalosporinase production. The mic(90)s of cefepime for Enterobacter species was three or more dilutions below the mic resistant category. The mic(90)s of all antimcrobials against Staphylococcus aureus, with the exception of ceftazidime and piperacillin, had mic(90) categories two or more dilutions below the resistant category. The activity of cefepime, piperacillin/tazobactam, imipenem, ciprofloxacin and gentamicin make them excellent candidates for the empirical therapy of serious infections due to aerobic Gram-negative bacilli and S aureus.     

Amoxapine-associated agranulocytosis with thrombocytosis occurring early during recovery

Agranulocytosis developed in a 35-year-old woman after she received 18 g of amoxapine, a tricyclic antidepressant, over 57 days. On the fifth day after cessation of amoxapine treatment, her platelet count rose from normal to a peak value of 999,000/mm3 on the 13th day. No cause for this thrombocytosis was apparent. Granulocytes appeared in the peripheral blood on the 15th day, and the thrombocytosis abated with the platelet count returning to a normal level by day 22. This confirms a previous report that amoxapine may be associated with agranulocytosis and suggests that thrombocytosis may occur as an early sign of recovery of the bone marrow in drug-associated toxic agranulocytosis.     

Study of the in vitro activity of amoxicillin/clavulanic acid and other beta-lactam antibiotics against Escherichia coli isolated from urine specimens

A total of 205 serial, unduplicated urinary isolates of Escherichia coli was collected from June through August 1998 in 2 community and 3 hospital laboratories. By using the NCCLS broth microdilution technique, their in vitro susceptibility to ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefuroxime axetil, ticarcillin/clavulanic acid and piperacillin/tazobactam was determined. One hundred and twenty isolates were from hospitalised patients, 85 from ambulatory, 129 community acquired and 76 nosocomial. Half of the nosocomial isolates were obtained from naturally produced and half from alternatively produced urine specimens. In general, the highest susceptibility rates, following NCCLS criteria, were found for piperacillin/tazobactam (93.2%) followed by cefuroxime (92.2%) and amoxicillin/clavulanic acid (82.9%). Ampicillin showed a clear bimodal distribution with a clear peak for the resistant population. The highest degree of ampicillin resistance was found in nosocomial isolates. Overall, ampicillin showed the lowest degree of susceptibility. Most of the ampicillin resistant isolates remained susceptible to piperacillin/tazobactam, cefuroxime and amoxicillin/clavulanic acid. In general, the community acquired isolates had higher susceptibility rates than the nosocomial isolates.     

Two cases of heparin-induced thrombocytopenia (HIT) and a review of the literature

We experienced two cases of heparin-induced thrombocytopenia (HIT) which occurred during unfractionated heparin treatment. The first patient was a 72-year-old man, who was admitted to our hospital because of sudden onset dyspnea in January 2000. He was diagnosed as having a pulmonary embolism and heparin was started. Nine days later, progressive embolization of the pulmonary artery and femoral vein was found and thrombocytopenia (platelet count 20 x 10(9)/l) was observed 14 days after that. Cessation of heparin and administration of argatroban resulted in progressive normalization of the platelet count. The second patient was a 62-year-old woman, who was admitted to our hospital in April 2001, with the chief complaint of sudden onset dyspnea. She was diagnosed as having acute left-sided heart failure and heparin was started. Fifteen 15 days later, thrombocytopenia (platelet count 17 x 10(9)/l) was observed. Cessation of heparin resulted in normalization of the platelet count. Both cases were positive for anti-heparin-platelet factor 4 (PF4) antibody. Here we report on the clinical course of two cases of HIT with a review of the literature.