Cholangiopathy after short-term administration of piperacillin and imipenem/cilastatin.

We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra-abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short-term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.     

Drug–laboratory interaction between beta-lactam antibiotics and the galactomannan antigen test used to detect mould infections

Several studies have demonstrated that piperacillin/tazobactam produces a false-positive result for the galactomannan antigen test. However, the most recent literature has demonstrated that this interaction is no longer a concern. There is little information regarding the drug–laboratory interaction with the generics of piperacillin/tazobactam or other broad-spectrum beta-lactams, such as ceftaroline, doripenem, imipenem/cilastatin, and meropenem. The purpose of this study was to determine if a drug–laboratory interaction exists with these antibiotics. Tests showed that one lot of imipenem/cilastatin by Hospira Healthcare India Private Limited produced a false-positive result for the galactomannan antigen test. All other medications tested, including piperacillin/tazobactam from seven manufacturers and imipenem/cilastatin by Hospira Inc., did not produce positive results. Since the reason for this drug–laboratory interaction with imipenem/cilastatin is unknown, more studies are needed to further investigate this interaction. Providers also should be educated of these findings: no drug–laboratory interaction with piperacillin/tazobactam and a possible drug–laboratory interaction with imipenem/cilastatin (Hospira Healthcare India Private Limited).     

哌拉西林钠/他唑巴坦钠治疗肺部感染的临床研究

目的　以亚胺培南 /西司他丁作为对照药物 ,评价哌拉西林钠 /他唑巴坦钠治疗中、重度肺部感染的有效性和安全性。方法　哌拉西林钠 /他唑巴坦钠 3.375 g静脉滴注 ,每 12 h一次 ,或亚胺培南 /西司他丁 0 .5 g静脉滴注 ,每 12 h一次 ,治疗中、重度肺部感染 ,疗程为 7- 14 d。结果　共治疗病人 90例 ,其中试验组 5 8例 ,对照组 32例。哌拉西林钠 /他唑巴坦钠试验组治疗中、重度肺部感染有效率 91.38% ,治愈率 81.0 4 % ,细菌清除率 89.4 6 % ,副作用发生率 3.4 5 % ;亚胺培南 /西司他丁对照组有效率 90 .6 3% ,治愈率 81.2 5 % ,细菌清除率 90 .0 0 % ,副作用发生率 3.13%。两组各率比较差异无显著性 (p>0 .0 5 )。结论　哌拉西林钠 /他唑巴坦钠是一高效、安全广谱抗菌药物 ,对中、重度肺部感染的疗效与亚胺培南 /西司他丁相似 ,两者副作用发生率相近     

Bacteremia due to Clostridium difficile

We describe a case of bacteremia due to Clostridium difficile, which was successfully treated by intravenous vancomycin. A 69-year-old woman was admitted to our hospital because of third degree burn injuries. She was treated with cefazolin for two weeks followed with flomoxef for one week before the operation (debridement and grafting of skin). On the third postoperative day high fever (temperature 40 degrees C), abdominal pain and severe watery diarrhea developed. Antibiotic-associated colitis with bacteremia was diagnosed presumptively, flomoxef was stopped, and oral and intravenous therapy with vancomycin was started. A blood culture taken before the administration of vancomycin yielded C. difficile accompanied with Enterococcus faecalis and Enetrococcus casseliflavus. A stool culture taken on the next day yielded C. difficile, and a stool latex agglutination test was also positive. The patient improved slowly. Parenteral vancomycin was discontinued after two weeks. One week later, the patient developed pneumonia, and imipenem/cilastatin was added. Soon after addition of the agent, she developed recurrent diarrhea despite continual oral vancomycin therapy. The fecal samples obtained at this time were positive for C. difficile by culture and positive for toxins A & B. She was satisfactorily treated with oral vancomycin for a total of four weeks. After the following two weeks, however, recurrence of diarrhea developed again, which rapidly decreased with oral vancomycin for seven days. The patient did well thereafter and was discharged. All three C. difficile isolates from blood and fecal specimens were positive for toxins A & B, and identified the same PCR ribotyping pattern.     

Cholestatic hepatitis as a rare side effect of therapy with ticlopidine

A 71-year-old man with chronic atrial fibrillation was treated with aspirin because of a right cerebral infarction. Oral anticoagulation was not initiated because of a secondary hemorrhagic transformation. Six years later after a left cerebral transient ischemic attack aspirin was replaced by ticlopidine. Two weeks after starting ticlopidine he experienced abdominal cramps and diarrhea. Also dark urine and gray-colored stools were noticed, so that the patient stopped taking ticlopidine. 40 days after starting ticlopidine he was admitted to our hospital because of cholestatic jaundice. Serum alkaline phosphatase (305 U/l) and gamma GT (143 U/l) were elevated, the total bilirubin was 18.6 mg/dl at peak. GOT and GPT were 2.7 fold increased. After exclusion of a viral infection and autoimmune disease liver biopsy was performed, which showed a centroacinar cholestasis compatible with a drug-induced liver damage. 79 days after discontinuation of the drug laboratory signs of cholestasis had disappeared. In patients in whom long-term therapy with ticlopidine is indicated regularly laboratory tests and clinical examinations should be done to recognize infrequent side effects such as the cholestatic hepatitis in time.     

Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin

Observations on 1,754 patients treated with imipenem/cilastatin in phase III dose-ranging studies in the United States were reviewed to determine risk factors for seizures. The patients were moderately to severely ill with numerous background disorders known to be associated with an increased risk of seizures. Fifty-two patients (3 percent) had seizures and in 16 (0.9 percent) of them the seizures were judged by the investigators to be possibly, probably, or definitely related to imipenem/cilastatin. An incidence of seizure of 2 to 3 percent was noted among patients treated with other antibiotics (usually including a beta-lactam in the regimen) at times when imipenem/cilastatin was not being given. The average time of onset of seizures for patients receiving imipenem/cilastatin was seven days after start of therapy. As with other beta-lactam antibiotics, central nervous system lesions and disorders including seizures and renal insufficiency were found to be strong risk factors for seizures. Imipenem/cilastatin dosages in excess of those currently recommended by the manufacturer, particularly in patients with renal insufficiency, were also associated with an increased risk of seizures. There was an association with Pseudomonas aeruginosa infection that remained statistically significant even after controlling for imipenem/cilastatin dosage as well as for the other factors indicated. A high background incidence of seizures in general in a group of severely ill patients makes it both difficult to assess the etiology of a seizure and important to consider the risk factors when choosing the appropriate dose of an antibiotic. Guidelines are presented for appropriate dosing of imipenem/cilastatin in relation to renal function, body weight, and infecting pathogen.     

Mucosal pharmacokinetics and pilot study of short course of parenteral imipenem in the eradication of Helicobacter pylori

Abstract Eradication of Helicobacter pylori infection is known to reduce the incidence of duodenal ulcer recurrence. The most commonly used regimen for H. pylori infection is triple antimicrobial therapy for 1-2 weeks. This treatment is associated with frequent side effects and hence unsatisfactory compliance. As in vitro data showed that H. pylori is sensitive to imipenem, the pharmacokinetics of this drug in the gastric milieu, and the clinical efficacy of imipenem with omeprazole in eradicating H. pylori infection were studied. Imipenem/cilastatin levels in serum, gastric secretion and gastric mucosa were assayed in four patients after intravenous injection of a bolus dose of 500 mg. The serum and gastric secretion levels of imipenem achieved were more than 10 times the minimum inhibitory concentration of the drug for H. pylori. Gastric mucosal levels of imipenem vary considerably with time, which probably indicates rapid elimination of the drug into the gastric lumen. In the second part of this study, imipenem/cilastatin was given intravenously for the first 2 days after diagnosis of H. pylori infection in patients with endoscopically confirmed duodenal ulcers. The patients were also treated with 4 weeks of omeprazole. Clearance of H. pylori was initially achieved at the end of 2 days in 20 out of 22 (91%) patients. However, when the biopsies were repeated at 8 weeks, recurrence of H. pylori infection was evident in 19 cases (86.3%) indicating a failure of eradication. It was concluded that imipenem/cilastatin in combination with omeprazole failed to eradicate H. pylori infection.     

Drug‐induced liver injury in a chronic hepatitis C patient treated by peginterferon,ribavirin and simeprevir

A 56‐year‐old male patient with chronic hepatitis C was treated with pegylated interferon (PEG IFN)‐α‐2b and ribavirin (RBV) for 72 weeks in 2006. The patient achieved an early virological response (EVR); however, hepatitis C relapsed 12 weeks after discontinuation of PEG IFN and RBV. In 2012, the patient was treated with a PEG IFN/RBV/telaprevir combination therapy. After 5 days of treatment, he suffered from a telaprevir‐associated skin rash on his body and four limbs. He chose to be treated with PEG IFN and RBV until 60 weeks. He again achieved EVR but no sustained virological response. In 2014, he was treated with PEG IFN/RBV/simeprevir combination therapy. He achieved rapid virological response, but after 6 weeks of therapy, a striking elevation of serum aminotransferase level was recorded with no accompanying skin rash; he was admitted to our hospital. PEG IFN/RBV/simeprevir was stopped, but sodium valproate (400 mg/day), which had been administrated for more than 10 years to prevent epilepsy was continued. Liver biopsy revealed typical features of drug‐induced liver injury. After stopping PEG IFN/RBV/simeprevir, serum aminotransferase levels soon returned to the normal range. We diagnosed this case to be simeprevir‐induced hepatitis clinically and histologically. Physicians need to stay alert to the possibility of drug‐induced liver injury in using simeprevir.     

Treatment of endocarditis due to Pseudomonas aeruginosa with imipenem.

Therapy for endocarditis due to Pseudomonas aeruginosa is complicated by the emergence of resistance during therapy, lack of universally available synergistic antimicrobial agents, and unacceptably high morbidity and mortality rates. The authors report a case of aortic valve endocarditis due to P. aeruginosa in which resistance to piperacillin developed during combined therapy with tobramycin. Bacteriologic cure was obtained with a combination of imipenem/cilastatin and tobramycin. The authors review six other cases of P. aeruginosa endovascular infections treated with imipenem.     

Fatal septic shock caused by transrectal needle biopsy of the prostate; a case report

A 46-year-old man refer to us because of hemospermia. The prostatic gland was normal in size and consistency at rectal examination. Serum prostate specific antigen was 7.04 ng/ml. Magnetic resonance imaging showed an area of low signal intensity on T2-weighted images in the left peripheral gland, possibly indicative of carcinoma. Transrectal prostate biopsy was performed after intravenous administration of piperacillin. He developed chills and fever (39 degrees C) the next morning following biopsy. He was taken unconscious into the hospital where a diagnosis of septic shock caused by Escherichia coli was made. Five days later, he died. His general condition deteriorated notwithstanding intensive treatment. Postmortem blood cultures were positive for a piperacillin resistant Escherichia coli. Histological examination of the biopsies showed a benign prostatic hyperplasia. Autopsy showed diffuse tissue damage in the heart, lung, liver and kidneys. The prostate had numerous microabscesses. Currently, transrectal prostate biopsy is considered a generally reliable procedure to detect adenocarcinoma of the prostate. Our case seems to the sixth case report of fatal complications.     

Glycogenic hepatopathy is an under‐recognised cause of hepatomegaly and elevated liver transaminases in type 1 diabetes mellitus

Glycogenic hepatopathy (GH) is an under‐recognised complication of type 1 diabetes mellitus (T1DM) not controlled to target resulting in hepatomegaly and elevated liver transaminases. We report the case of a 19‐year‐old man with T1DM not controlled to target who presented with abdominal pain, hepatomegaly and deranged liver transaminases. He was subsequently diagnosed with GH on liver biopsy, with the mainstay of treatment being reduction in caloric intake and insulin.     

Hepatic involvement in a liver transplant recipient with disseminated cryptococcosis

Abstract: Cryptococcosis occurs primarily in immunocompromised patients such as organ transplant recipients. Central nervous system and pulmonary infections are documented most frequently; hepatic involvement is rarely reported. We report a case of early hepatic cryptococcosis in a 54-year-old male liver transplant recipient. Two weeks after orthotopic liver transplant, he was readmitted with fever, malaise, diarrhea, and progressive pulmonary infiltrates. On admission, liver-associated enzymes were decreased from those at discharge after transplantation. Blood and bronchoalveolar lavage cultures were positive for Cryptococcus neoformans . Despite treatment with amphotericin B and flucytosine, the patient developed both marked cholestasis and transaminase elevation. A liver biopsy performed 22 days after admission revealed numerous yeast-like organisms in hepatic sinusoids consistent with C. neoformans . Despite treatment, the patient died 55 days after admission and 66 days after transplantation. Our case illustrates hepatic involvement of cryptococcal infection within the first month following transplantation.     

Cost-effectiveness of ceftazidime or imipenem/cilastatin versus ceftriaxone+aminoglycoside in the treatment of febrile episodes in neutropenic cancer patients in Germany

Summary A three-pronged cost-effectivess analysis of the treatment of febrile episodes in neutropenic cancer patients was conducted. It included a review of 37 randomized, controlled studies in the MEDLINE and EMBASE databases (1980–1996). Clinical outcomes as well as costs of treatment with imipenem/cilastatin, ceftazidime and ceftriaxone+aminoglycoside were compared. Primary therapy and modification, respectively, were successful in 62 and 27% of patients treated with imipenem/cilastatin, in 56 and 31% with ceftazidime and in 41 and 13% with ceftriaxone+aminoglycoside. From the perspective of a 1,800-bed teaching hospital, the average overall cost per successfully treated patient was DM 7,475 with imipenem/cilastatin, DM 7,810 with ceftazidime and DM 8,963 with ceftriaxone+netilmicin (DM 1=USD 0.56; 7/97). The costs for the German national economy were imipenem/cilastatin DM 23,828, ceftazidime DM 24,985 and ceftriaxone+netilmicin DM 29,838.     

Acute liver failure following the use of ecstasy (MDMA)

The use of "ecstasy" (Methylenedioxymethamphetamine) as a recreational drug is increasing in europe since the 1980's. Aside intended psychological effects the use of ecstasy can be followed by symptoms of intoxication; complications include toxic hepatic damage up to acute hepatic failure. This case-report is about a 17-year old female patient who regularly used "ecstasy" over a six-month period. Two days after the last use of "ecstasy", she reported to her general practitioner with nausea, vomiting, abdominal pain and jaundice. Within 10 days the patient developed acute liver failure. With criteria for liver transplantation fulfilled she was listed for orthotopic liver transplantation of high urgency which was carried out only one day later. Histological examination of the explanted liver showed evidence for a toxic fulminant hepatitis. After transplantation the patient made a full recovery and was released from hospital on day 26 after transplantation. At the first control after six months the patient was in good physical and nutritional condition, serological parameters were normal and ultrasound examination of the transplanted liver was unremarkable. The ethiopathology of "ecstasy"-induced hepatotoxicity, which can occur dose-independently with a symptom-free period from days to weeks after ingestion is not yet fully understood. Possible mechanisms of hepatic damage include influence of MDMA on body temperature regulation, harmful effects of the substance or further components of the "ecstasy"-tablets on the liver cell or a genetic vulnerability of some individuals against amphetamines and amphetamine derivates. There are no parameters existing which could predict the course and severity of "ecstasy"-induced hepatopathy. Especially in young patients with symptoms of hepatic damage frequent controls of clinical status and relevant laboratory parameters are of great importance. Patient transfer to a specialised centre should follow as early as possible; at the latest, when coagulopathy occurs.     

A case of probable bacterial translocation-associated sepsis in healthy adult

We report a patient with bacterial translocation-associated sepsis who was healthy and did not have any related-background. The 57-year-old male had been well until 16 hours before admission, when nausea and vomiting gradually developed and increased in intensity. In the morning of May 22, 2002, he had shaking chills, temperature of 38.6 degrees C and watery diarrhea, and was admitted to Kawasaki Municipal Hospital. On admission, temperature was 40.7 degrees C but otherwise physical examination revealed no particular abnormality. Laboratory data showed total white blood cells of 28,400/microliter, platelet count of 130,000/microliter, creatinine of 2.0 mg/dl and C-reactive protein of 7.5 mg/dl. 1 g of cefmetazole was administered every eight hours. In the early morning of May 23, he suddenly went into shock. At that time, laboratory findings revealed total white blood cells of 33,700/microliter, platelet count of 65,000/microliter, C-reactive protein of 24.9 mg/dl, creatinine of 5.6 mg/dl and serum potassium concentration of 5.7 mEq/l. Gram positive cocci and gram negative rods were isolated from blood culture obtained on admission. Cefmetazole was changed to 1.5 g/day of imipenem/cilastatin sodium and 600 mg/day of clindamycin. In addition, hemodialysis and endotoxin removal with an adsorbent column using polymyxin B were performed. Bacteria detected in the blood on admission were identified as Klebsiela oxytoca and Enterococcus faecium. Imipenem/cilastatin sodium and clindamycin were continued for 13 days. The patient recovered fully and was discharged on June 11. This case suggests that bacterial translocation-associated sepsis might occur even in a hitherto healthy adult.     

A surgically treated case of ileus caused by small intestinal tuberculosis during treatment for pulmonary tuberculosis

A 44-year-old man consulted medical clinic, complaining of cough and sputum. Then he was admitted to our hospital, because of positive acid-fast bacilli in his sputum and positive PCR (polymerase chain reaction) for Mycobacterium tuberculosis. Combined use of isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide (PZA) was started. But 4 days after starting treatment, we had to suspend tuberculosis chemotherapy because of hepatopathy. Since then he started to complain epigastralgia and vomiting. Plain abdominal X-ray and abdominal computed tomography (CT) led to a diagnosis of ileus. Inspite of insertion of ileus tube symptoms of ileus did not improve. Small bowl series showed severe stenosis at ileum end, necessitating jejunectomy. Macroscopic study revealed a ring ulcer and multiple epithelioid cell granuloma with Langhans' giant cells was detected histopathologically. PCR for M. tuberculosis of extracts from ileum was positive. Therefore the patient was diagnosed small intestinal tuberculosis. Treatment was continued by the combination of INH, RFP, EB, and the symptoms markedly improved. There have been no sign of recurrence since the end of the 6-month treatment for tuberculosis.     

A case of prominent hepatic cholestasis developing to hepatic failure in lambda-AL amyloidosis

We report a case of lambda-AL amyloidosis which manifested prominent hepatic cholestasis. The patient was a 71-year-old Japanese male who was admitted to our hospital because of abdominal distension and jaundice. Laboratory examination revealed a marked deterioration of liver function with cholestasis. Gastric biopsy revealed amyloid deposition. Under a diagnosis of primary amyloidosis he was treated with corticosteroid and dimethylsulfoxide. However, jaundice progressed, renal function deteriorated rapidly, and he died two weeks after admission. Autopsy revealed a profound deposition of lambda-AL amyloid not only in the liver but also in the kidneys, spleen, lungs, heart and intestine.     

Imipenem/cilastatin versus gentamicin/clindamycin: a cost effectiveness study

A previously published clinical trial was used for analysis of costs for antibiotic treatment in patients with serious bacterial infections requiring the use of injectable broad spectrum antibiotics. The patients were randomized to receive imipenem/cilastatin 500/500 mg q6h (77 patients of which 56 were evaluable for efficacy) or clindamycin 600 mg q6h plus gentamicin 1.5 mg/kg with dose intervals determined by serum concentration monitoring (86 patients of which 62 were evaluable for efficacy). An analysis of the costs for antibiotics, including drugs, equipment and staff for administration and gentamicin serum concentration assays, showed that imipenem/cilastatin was not more expensive than gentamicin plus clindamycin per treatment day although the drug cost was considerably higher for imipenem/cilastatin. Since imipenem/cilastatin was significantly more effective and caused less frequent adverse reactions than gentamicin plus clindamycin it was more cost-effective in the patients studied.     

美罗培南治疗急性细菌性感染临床观察

目的：评价美罗培南治疗细菌性感染的安全性及有效性。方法：采用随机对照试验方法。试验组美罗培南500mg-1g,静脉点滴,每12h1次,对照组亚胺培南－西司他丁500mg/500mg-1g/1g,每12h1次,静脉点滴。疗效均为7－14d。结果：美罗培南组及亚胺培南－西司他丁组分别有42例及41例可评价疗效。两组有效率分别为88．1％（37／42）及85．4％（35／41）。对各种致病菌感染有效率分别为85．3％（29／34）和82．4％（28／34）。两组治疗前分离株分别为37株及38株。治疗后细菌清除率分别为81．1％（30／37）和84．2％（32／38）。两组安全性评价分别为44例及41例,不良反应发生率分别为13．6％（6／44）与12．2％（5／41）。两组经统计学处理差异无显著性（P＞0．05）。结论：美罗培南治疗急性细菌性感染疗效好,较安全。     

Spondylodiscitis after facet joint steroid injection: a case report and review of the literature

Spondylodiscitis is a rare complication after facet joint steroid injection. This article presents a 78-y-old male with chronic back pain and facet joint arthritis who developed Pseudomonas aeruginosa L2-L3 and L3-L4 spondylodiscitis after computed tomography-guided facet joint steroid injection. Magnetic resonance imaging, fine needle aspiration and cultures confirmed the diagnosis. The patient was treated with intravenous administration of amikacin, and imipenem plus cilastatin for 4 weeks, followed by oral administration of ciprofloxacin for another 10 weeks. Sterile preparation prior to facet joint steroid injection should be stressed. To the best of our knowledge, this is the only reported case of iatrogenic spondylodiscitis after facet joint steroid injection. This iatrogenic complication should be considered in the risk-benefit analysis of facet joint diagnostic or therapeutic injections.