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G Marklein

Publications and source records attributed to G Marklein.

At least 19 recordsLinked to original sources
PubMed2005

[Bacterial infections in pediatric cancer patients].

Increased dose intensity and a better long term survival can not be reached in pediatric oncology without the judicious use of antibiotics. During periods with profound neutropenia and between intensive chemotherapy cycles are bacterial infections capable of disturbing the patients' quality of life; they may cause an acute life threatening situation and lead to a substantial increase in expenditures and consumption of ressources in supportive care. The non-judicious use of antibacterials may face the patient to an increased risk of adverse events and fosters the selection of resistant bacteria. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for antibacterial therapy in pediatric oncology patients based upon the available literature and the clinical experience of the authors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein.

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15-1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16-0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13-0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35-5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann-Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152-1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94-445) for patients with fever of unknown origin, 177 pg/ml (IR, 142-208) for patients with non-microbial fever and 942 pg/ml (IR, 181-2,807) for patients with bacteremia. Using the Mann-Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.

Adult↗
PubMed2004

Wound infection due to Absidia corymbifera and Candida albicans with fatal outcome.

A case of a mixed infection due to Candida albicans and the zygomycete Absidia corymbifera in a 38-year-old, previously healthy, Caucasian male is presented. The infection developed following serial rib fractures, and ruptures of kidney, liver and biliary tract as well as a pancreatic contusion resulting from a traffic accident. During intensive care treatment the patient underwent several surgical procedures but subsequently experienced multi-organ failure and sepsis. Some weeks later, fungal growth was observed macroscopically on the patient's skin and wounds. From wound swabs C. albicans and A. corymbifera were grown. Histopathology of abdominal tissue yielded pseudohyphae and coenocytic hyphae. Although surgical debridement and antifungal treatment with amphotericin B and 5-flucytosine were started immediately, the patient died in therapy-refractory septic multi-organ failure.

Absidia↗
PubMed2003

Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison.

GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues. Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined. PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response. RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047). If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added. All patients still febrile then received meropenem, teicoplanin and amphotericin B. With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005). The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010). CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies.

Adolescent↗
PubMed2003

Fatal pulmonary scedosporiosis.

We report on a case of scedosporiosis in a 72-year-old German woman. Her disease started with a purulent ulceration of unknown course at her left foot. Soon after onset of oral antibacterial therapy she needed in-hospital treatment because of an acute pneumonia. The infection progressed despite the application of different antibiotics. Microscopic examination of tracheal fluid revealed fungal hyphae and therefore treatment with itraconazole was initiated. However, the patient developed renal failure, required mechanical ventilation and finally died in treatment-resistant septic shock. Post-mortem Scedosporium apiospermum was cultured from lung tissue taken during autopsy. This is the fourth case of human infection caused by Scedosporium species diagnosed in our laboratory during the last 4 years.

Aged↗
PubMed2002

Low frequency of enteric infections by Salmonella, Shigella, Yersinia and Campylobacter in patients with acute leukemia.

BACKGROUND: Several authors found that isolation of Salmonella, Shigella, Yersinia and Campylobacter spp. (SSYC) from stool cultures after the 3rd day of hospitalization is a rare event. The significance of enteric infections caused by these pathogens has not been systematically investigated in severely immunosuppressed patients with acute leukemia. PATIENTS AND METHODS: We screened all patients treated on the leukemia ward of a university medical center. A total of 1,185 stool cultures from 371 episodes of diarrhea, mostly following myelosuppressive chemotherapy, were examined for the complete range of classic bacterial enteric pathogens (i.e. SSYC). RESULTS: Only three (0.25%) cultures from one patient were positive for Salmonella enteritidis. This patient suffered from cholangitis. S. enteritidis could also be detected by liver biopsy. Other infections by classic enteric pathogens were not observed. CONCLUSION: Symptomatic infections by classic bacterial enteric pathogens in hospitalized patients with acute leukemia are very rare. Stool cultures for these pathogens cannot be recommended as a routine test in uncomplicated diarrhea occurring after the 3rd hospital day.

Acute Disease↗
PubMed2002

Case Report. Maxillary sinus infection due to Emericella nidulans.

Fungal infections of the maxillary sinus are frequently caused by Aspergillus species, particularly A. fumigatus. In otherwise healthy persons there is an association with overfilling of dental root canals, when zinc-containing filling materials were used. Below, a maxillary sinus aspergilloma is reported in a young immunocompetent female patient caused by Aspergillus (Emericella) nidulans.

Adult↗
PubMed2002

Pseudomonas aeruginosa outbreak in a haematology-oncology unit associated with contaminated surface cleaning equipment.

An outbreak of six cases of hospital-acquired Pseudomonas aeruginosa infections (two pneumonia two septicaemia, two skin/wound infection) occurred between August and September 2000 in an adult haematology-oncology unit at a tertiary-care centre. During the outbreak, hospital-acquired infection (HAI) incidence density rates rose from 29.4 to 62.3 (P < 0.05) infections per 1000 days at risk (i.e., neutropenic days). A systematic outbreak management system was actioned in accordance with a German draft guideline. Multiple samples from the patients' environment were tested for the presence of P. aeruginosa. A total of 4.5% of samples from sanitary equipment and 20.0% of samples from surface cleaning equipment were found to be contaminated with P. aeruginosa. Genotypic analysis by pulsed-field gel electrophoresis showed different patterns for all (N = 6) of the patient isolates, however, two of the patient isolates were identical in comparison with environmental isolates from cleaning equipment (four samples) and sanitary equipment (one sample). Our investigation revealed that the cleaning staff had used cleaning solution instead of disinfectants for decontamination of the patients' environment. The outbreak was terminated after re-adoption of surface disinfection, application of sterile filters on taps and shower heads, chemical disinfection of the washbasin drains, and appointment of a hospital hygiene nurse to a previously unfilled position. After institution of the control measures, HAI incidence densities decreased to pre-outbreak level. This investigation emphasizes the need to carefully evaluate cleaning and disinfection practices for patient care, particularly in neutropenic patients.

Adult↗
PubMed2001

Clostridium difficile infection in patients with neutropenia.

Clostridium difficile is the most important cause of nosocomial infectious diarrhea. The importance of C. difficile-associated diarrhea (CDAD) has been poorly investigated in patients with neutropenia who have hematologic malignancies. A retrospective chart review of all patients treated in the leukemia ward of a university medical center during 1991-2000 determined that 875 courses of myelosuppressive chemotherapy were administered. CDAD occurred in 7.0% of all cycles. In 8.2% of the patients, severe enterocolitis developed. Two patients died while they had diarrhea. However, in no patient was C. difficile infection clinically considered to be the primary cause of death. The response rate to oral metronidazole was 90.9%. These data indicate that C. difficile infection is not rare and should be suspected whenever a hospitalized patient with neutropenia develops diarrhea. Oral metronidazole can be recommended as initial drug of choice for treatment of patients with neutropenia who have hematologic malignancies and CDAD.

Adolescent↗
PubMed2001

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients.

The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens. This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients. In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%). The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs. 52.4%, P=0.039), and 35.0% in documented infections. In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes. Four patients died of causes related to infection. Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic. Toxic side effects were minimal. The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients.

Adolescent↗
PubMed2001

[Antimicrobial prophylaxis of bacterial infections in pediatric oncology patients].

Bacterial infections are still a major challenge in the treatment of pediatric cancer patients. Considering the evidence in the literature and published consensus opinions of experts the following strategies of antibacterial chemoprophylaxis (ABCP) in pediatric cancer patients can be recommended (or not recommended): Accompanying the implantation of a ventriculoperitoneal shunt (or a Rickham-reservoir) ABCP is recommended, until prospective controlled studies including pediatric cancer patients have investigated this issue. In bone marrow or stem cell transplant recipients, the prophylactic administration of penicillin should be considered, if severe oral mucositis is a common adverse event in cancer departments with high rates of penicillin-susceptible strains of Streptococcus viridans. Prospective surveillance of resistant bacterial pathogens should be an indispensable tool of quality control in pediatric oncology departments. The risk of infection with antimicrobial-resistant isolates should be balanced against the real benefit of antimicrobial prophylaxis in every instance. ABCP should neither be given during implantation nor during prolonged usage to prevent bacterial infection of a central venous access device (unproven efficacy and potential hazards of Vancomycin-resistant gram-positive infections). The oral administration of non-absorbable ABCP or Trimetoprim-Sufomethoxazole is not recommended for the prevention of bacterial infections (unproven efficacy) and no recommendation can be given for the oral ABCP with chinolones (lacking data, risk of antimicrobial resistance).

Adolescent↗
PubMed2001

Severe abdominal infections in neutropenic patients.

Abdominal infections are an important cause of morbidity and mortality in neutropenic patients. We present a retrospective series of 16 patients, mostly with acute leukemia, who developed severe abdominal infections during chemotherapy-induced neutropenia between 1991 and 1997. The frequency among patients with acute leukemia was 2.35% (13 of 553). Thirteen patients presented with enterocolitis and 3 patients presented with cholecystitis. Eight patients died. Bacteremia was present in 6 patients, 4 patients suffered from proven or strongly suspected fungal infections, and 1 patient suffered from cytomegalovirus infection. Early surgical management was required in a patient with intestinal obstruction, whereas other patients could be managed conservatively. Two patients with acute cholecystitis were treated with antibiotics until the end of neutropenia and then were resected. Severe abdominal injections in neutropenic patients, which are often fatal, were caused by nonbacterial microorganisms in one-fourth of the cases and could be managed conservatively in most instances.

Abdomen↗
PubMed2001

Meropenem versus ceftazidime as empirical monotherapy in febrile neutropenia of paediatric patients with cancer.

This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients.

Bacterial Infections↗
PubMed2000

[Scedosporiosis of the brain with fatal outcome after traumatizatio of the foot. case report].

A 33 year old German man suffered from a wound of his foot after an accident. He developed an osteomyelitis. From wound probes Scedosporium apiospermum could be isolated for several times. Some weeks later a cerebral lesion could be diagnosed. The lesion was extirpated and again S. apiospermum could be cultured from the cerebral probes. A few weeks later the patient died and some new cerebral lesions could be diagnosed by CT-scan.

Adult↗
PubMed1999

Fungal surveillance cultures during antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia.

Fungal colonization has been associated with an increased rate of invasive fungal infections in neutropenic patients. This study evaluates weekly fungal surveillance cultures from the oropharyngeal and perianal space as well as other suspected sites in 219 courses of myelosuppressive chemotherapy with itraconazole antifungal prophylaxis in 116 neutropenic patients with acute leukaemia. Itraconazole was given from the start of chemotherapy in one of six different dosing regimens. Fungal colonization occurred in 68 (31%) of courses, which was lower than in a historical control group without prophylaxis (53%, P = 0.004). Twenty-six per cent of these 116 isolates had a growth rate of more than 50 colony forming units (CFU) per culture. Candida glabrata (51%), Candida albicans (18%) and Candida krusei (4%) were the most frequently isolated species. Higher median itraconazole trough concentrations were associated with a lower growth rate in the cultures (< or = 50 CFU/culture versus > 50 CFU/culture): 710 (430-1180) ng ml-1 versus 900 (560-1650) ng ml-1 (P = 0.015). The use of itraconazole solution--compared with capsules--led to a reduced growth rate (P = 0.035). In conclusion, compared with historical controls itraconazole antifungal prophylaxis reduces the incidence and the extent of fungal colonization during neutropenia in patients with acute leukaemia.

Acute Disease↗
PubMed1999

Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole.

This study analyses invasive fungal infections in neutropenic patients with haematological malignancies during antifungal prophylaxis with itraconazole. From September 1994 to December 1998 20 patients developed fungal infections. Two patients suffered from disseminated infections by yeasts and 18 patients suffered from pulmonary infections by moulds (eight proven, 10 highly probable in high-resolution CT scans). In these patients the itraconazole trough concentrations exceeded 500 ng ml-1 (measured by high performance liquid chromatography) significantly less often (median 48%, interquartile range 0-100%) than in another group of 150 leukaemia patients without invasive fungal infections who received 287 courses of prophylaxis with itraconazole at our institution (median 100%, interquartile range 38-100%, P = 0.039). Twelve patients died, six of these had refractory disease. Patients with fatal invasive fungal infections had lower median itraconazole concentrations immediately before occurrence of the infection than patients with non-fatal infections: 120 (0-478) ng ml-1 versus 690 (305-1908) ng ml-1 (P = 0.039). In conclusion, this analysis of breakthrough invasive fungal infections during prophylaxis with itraconazole demonstrates that patients with itraconazole trough concentrations below 500 ng ml-1 were significantly more likely to develop fungal infections and that the last itraconazole trough concentration before occurrence of the infection was significantly lower in patients with fatal invasive fungal infections.

Adult↗