colistin and Neutropenia

A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with Kytococcus sedentarius during neutropenia following induction chemotherapy for acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure of broad-spectrum antibiotics probably made it possible for this normally harmless commensal to penetrate the gut, spread through the blood stream, and invade the lungs.

Topics: Actinomycetales; Actinomycetales Infections; Acyclovir; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Translocation; Cefepime; Cephalosporins; Clostridium Infections; Colistin; Cytarabine; Daunorubicin; Drug Therapy, Combination; Etoposide; Fatal Outcome; Hemoptysis; Humans; Hydroxyurea; Immunocompromised Host; Intestinal Mucosa; Leukemia, Myeloid, Acute; Male; Metronidazole; Middle Aged; Neutropenia; Pneumonia, Bacterial; Superinfection; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication.

Topics: Acute Disease; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Therapy, Combination; Humans; Infection Control; Infections; Leukemia; Multicenter Studies as Topic; Neutropenia; Norfloxacin; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987-1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial--combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0.001) and neutropenic days on intravenous antibiotics (P < 0.001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 700 [corrected] neutropenic episodes. Thirty-five of the 111 (31%) isolates were ciprofloxacin-resistant, involving 5% of the neutropenic episodes [corrected].

Topics: Adolescent; Adult; Aged; Antibiotic Prophylaxis; Bacterial Infections; Bone Marrow Transplantation; Ciprofloxacin; Colistin; Drug Therapy, Combination; Humans; Middle Aged; Neomycin; Neutropenia; Statistics, Nonparametric; Transplantation Conditioning; Treatment Outcome

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990-1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar. There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children -48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

Topics: Adult; Analysis of Variance; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Bacteremia; Child; Colistin; Fluconazole; Fungemia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Ofloxacin; Penicillin V; Penicillins; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia, oral pefloxacin plus vancomycin (PV) (n = 76) or gentamicin, colistin sulphate and vancomycin (GCV) (n = 74) were administered in a randomised double-blind study. Infections were significantly less severe in the PV than in the GCV group. Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GCV. Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV, because of fewer infections with Staphylococcus species and enterobacteriaceae. Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group. Thus, PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients, despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract.

Topics: Adult; Aged; Antineoplastic Agents; Bacterial Infections; Colistin; Double-Blind Method; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Middle Aged; Neutropenia; Pefloxacin; Vancomycin

In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication.

Topics: Acute Disease; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Therapy, Combination; Humans; Infection Control; Infections; Leukemia; Multicenter Studies as Topic; Neutropenia; Norfloxacin; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Preliminary results are presented of an ongoing, prospective, randomized, study comparing ofloxacin, ciprofloxacin and co-trimoxazole/colistin for the prevention of infection in patients with acute leukaemia. The results for 59 patients (median age 47 years, range 21-72) included 88 episodes of neutropenia, each associated with a course of cytotoxic therapy. The main factor measured was the time elapsed from the beginning of neutropenia (neutrophils less than 500/microliter) until the first infectious febrile episode. The median time for the period was 12 days (range 1-56) for the cotrimoxazole/colistin group, 15 days (range 1-38) for the ofloxacin group and 20 days (range 1-36) for the ciprofloxacin group (differences not significant). Microbiologically proven major infections occurred in 10/27 treatment courses with co-trimoxazole/colistin 7/31 courses with ofloxacin and 7/30 courses with ciprofloxacin (P not significant). These were mostly due to Gram-positive cocci. There were no Gram-negative infections in the quinolone groups compared with one major Pseudomonas aeruginosa infection in the co-trimoxazole/colistin group. No Pneumocystis carinii infections were encountered. Adverse reactions associated with co-trimoxazole/colistin required discontinuation of medication in 11/27 treatment courses because of compliance problems, skin reactions or gastrointestinal intolerance. There were significantly fewer discontinuations in the ofloxacin (n = 2) and in the ciprofloxacin groups (n = 3). Major side effects of the quinolones included persistent icterus in one patient receiving ofloxacin and psychiatric symptoms in one patient receiving ciprofloxacin. It is concluded from these data that there were no statistically significant differences between the three treatment groups in respect of the prevention of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Ciprofloxacin; Colistin; Humans; Neutropenia; Ofloxacin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Norfloxacin has been compared to placebo (136 patients), sulfamethoxazole plus trimethoprim (SXT, 72 patients) and oral vancomycin plus colistin (V/C, 61 patients) for the prevention of alimentary tract-associated infections during and after induction chemotherapy. These patients were evaluated for the safety and tolerability of each regimen by clinical and laboratory means. Most neutropenics involved, regardless of the regimen, experienced at least one adverse experience. The majority were felt to be unrelated to prophylactic study drug therapy. Of 139 patients who received norfloxacin, only two had drug-related adverse experiences, compared to two of 35 receiving SXT, five of 28 for VC, and none of 67 receiving placebo. In evaluating adverse experiences considered possibly drug related, 19 occurred on norfloxacin compared to 13 for placebo. Among neurologic adverse experiences, only one possibly related to norfloxacin occurred (confusion), while three occurred on placebo (confusion, decreased auditory acuity and hallucinations). Generally, no significant differences were seen between any of the regimens except for a higher frequency of diarrhea in those receiving V/C.

Topics: Agranulocytosis; Bacterial Infections; Clinical Trials as Topic; Colistin; Diarrhea; Gastrointestinal Diseases; Humans; Leukemia; Neutropenia; Norfloxacin; Skin Diseases; Sulfamethoxazole; Trimethoprim; Vancomycin

Topics: Acute Disease; Adult; Anti-Infective Agents; Ciprofloxacin; Clinical Trials as Topic; Colistin; Drug Combinations; Drug Therapy, Combination; Humans; Infection Control; Leukemia; Neomycin; Neutropenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Antineoplastic Agents; Clinical Trials as Topic; Colistin; Gentamicins; Humans; Leukemia; Middle Aged; Neutropenia; Nystatin; Sepsis; Vancomycin

43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

Topics: Acute Disease; Adult; Aged; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Drug Therapy, Combination; Female; Framycetin; Humans; Leukemia; Male; Middle Aged; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Thirty-eight uninfected patients undergoing bone marrow transplantation were assigned at random to receive prophylactic granulocyte transfusions and oral nonabsorbable antibiotics (group 1) or oral nonabsorbable antibiotics alone (group 2) when their neutrophil count fell below 0.5 x 10(9)/liter. The two groups were comparable in terms of age, sex, underlying disease, immunosuppressive therapy and days of neutropenia. There were three cases of septicemia (all due to gram-positive organisms) in group 2 and none in group 1 (p = 0.23). There was no difference in the incidence of other documented infections, and survival between the two groups was comparable. Recipients of prophylactic granulocyte transfusions had a significantly higher incidence of cytomegalovirus (CMV) infections (13 of 18 versus six of 17, p = 0.043). These data suggest that prophylactic granulocyte transfusions may prevent septicemia, have no effect on other infections or survival in patients undergoing bone marrow transplantation, and are associated with a higher incidence of CMV infection. Oral nonabsorbable antibiotics alone are equally effective in preventing serious infections in bone marrow transplant recipients.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Blood Transfusion; Bone Marrow Transplantation; Child; Colistin; Cytomegalovirus Infections; Evaluation Studies as Topic; Female; Granulocytes; Humans; Infection Control; Male; Middle Aged; Neutropenia; Nystatin; Random Allocation; Transplantation, Homologous; Vancomycin

A randomized study of intestinal decontamination was undertaken in 68 children with leukemia and solid tumours. Framycetin, colymycin, nystatin, and metronidazole were given in 35 neutropenic episodes in 33 children, while co-trimoxazole and lactobacilli preparation were administered in 35 episodes in 35 children. The diseases, severity of neutropenia, and incidence of infection at entry into study were comparable in the two groups. There was no significant difference in the incidence of infections developing during the phase of neutropenia. The median and range of time required to recover from neutropenia were also not different. Co-trimoxazole and lactobacilli were significantly better tolerated, there being no nausea and vomiting, no refusal to take medication, no dose reduction or change to an alternative regimen. We conclude that co-trimoxazole and lactobacilli preparation improve quality of life during a neutropenic episode and have the additional advantage of being relatively inexpensive.

Topics: Agranulocytosis; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Biological Products; Child; Child, Preschool; Colistin; Drug Combinations; Framycetin; Humans; Lactobacillus; Neoplasms; Neutropenia; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

30 patients with acute leukaemia being treated with cytotoxic drugs were investigated in a randomised trial to determine whether oral administration of co-trimoxazole in addition to non-absorbable antibiotics would reduce the rate of infection. Three significant differences were observed between the co-trmoxazole and the control groups: (i) 15 of the 16 (94%) control patients but only 8 of the 14 (57%) patients on co-trimoxazole developed infections and required additional antibiotics intravenously; (ii) although the duration of severe neutropenia (neutrophils less than 0.1 times 10(9)/1) was similar in the two groups, control patients required intravenous antibiotics on average after 2 days of neutropenia, whereas patients receiving co-trimoxazole required these only after 12 days; and (iii) the only 2 patients who died of infection were in the control group. Prophylaxis with co-trimoxazole is important in preventing or delaying the development of infection in neutropenic patients receiving therapy for acute leukaemia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Clinical Trials as Topic; Colistin; Cross Infection; Drug Combinations; Drug Therapy, Combination; Framycetin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Middle Aged; Neutropenia; Nystatin; Prospective Studies; Research Design; Sulfamethoxazole; Trimethoprim

The 68-year-old patient presented with fever, general malaise and physical weakness in neutropenia during a known relapse of acute myeloid leukaemia after allogeneic stem cell transplantation.. Due to immune suppression, an empiric antibiotic therapy with piperacillin/tazobactam was started. The 4MRGN screening was positive. For this reason, therapy was switched empirically to ceftazidime/avibactam plus colistin. A tongue ulcer with abscess formation and phlegmonous soft tissue reaction was revealed as the focus of the infection. Several microbiological probes including a blood culture discovered. Die Vorstellung der 68-jährigen Patientin erfolgte bei hohem Fieber, allgemeinem Unwohlseisn und körperlicher Schwäche in der Neutropenie bei Rezidiv einer akuten myeloischen Leukämie nach allogener Stammzelltransplantation.. Aufgrund der bestehenden Immundefizienz wurde eine kalkulierte antibiotische Therapie mit Piperacillin/Tazobactam begonnen. Bei positivem 4MRGN-Screening wurde diese kalkuliert auf Colistin und Ceftazidim/Avibactam umgestellt. Diagnostiziert wurde ein Zungenulkus mit Abszessbildung und phlegmonöser Weichteilreaktion. In mehreren mikrobiologischen Proben, inklusive einer Blutkultur, gelang der Nachweis eines. Vierfach multiresistente gramnegative Bakterien (4MRGN) sind aufgrund ihrer Resistenz gegenüber 4 bakterizid wirkenden Hauptantibiotikagruppen (Acylureidopenicilline, Cephalosporine der 3. Generation, Carbapeneme, Fluorchinolone) nur schwer therapierbar. Der vorliegende Fall zeigt für Cefiderocol eine gute klinische Wirksamkeit – auch bei Erregern, die gegen Antibiotika wie Colistin und Ceftazidim/Avibactam resistent sind und er verdeutlicht, wie wichtig eine antibiogrammgerechte Therapie ist.

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Cefiderocol; Ceftazidime; Cephalosporins; Colistin; Communicable Diseases; Drug Combinations; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Neoplasm Recurrence, Local; Neutropenia

Gram-negative bacteria are responsible for an increasing number of deaths caused by antibiotic-resistant infections

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Biosynthetic Pathways; Colistin; Drug Resistance, Bacterial; Ethanolamines; Genes, Bacterial; Genome, Bacterial; Gram-Negative Bacteria; Mice; Microbial Sensitivity Tests; Multigene Family; Neutropenia; Plasmids; Transferases (Other Substituted Phosphate Groups)

The discovery of mobile colistin resistance mcr-1, a plasmid-borne polymyxin resistance gene, highlights the potential for widespread resistance to the last-line polymyxins. In the present study, we investigated the impact of mcr-1 acquisition on polymyxin resistance and biological fitness in Klebsiella pneumoniae.. K. pneumoniae B5055 was used as the parental strain for the construction of strains carrying vector only (pBBR1MCS-5) and mcr-1 recombinant plasmids (pmcr-1). Plasmid stability was determined by serial passaging for 10 consecutive days in antibiotic-free LB broth, followed by patching on gentamicin-containing and antibiotic-free LB agar plates. Lipid A was analysed using LC-MS. The biological fitness was examined using an in vitro competition assay analysed with flow cytometry. The in vivo fitness cost of mcr-1 was evaluated in a neutropenic mouse thigh infection model.. Increased polymyxin resistance was observed following acquisition of mcr-1 in K. pneumoniae B5055. The modification of lipid A with phosphoethanolamine following mcr-1 addition was demonstrated by lipid A profiling. The plasmid stability assay revealed the instability of the plasmid after acquiring mcr-1. Reduced in vitro biological fitness and in vivo growth were observed with the mcr-1-carrying K. pneumoniae strain.. Although mcr-1 confers a moderate level of polymyxin resistance, it is associated with a significant biological fitness cost in K. pneumoniae. This indicates that mcr-1-mediated resistance in K. pneumoniae could be attenuated by limiting the usage of polymyxins.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Female; Genetic Fitness; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Neutropenia; Plasmids; Polymyxins

Patients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapy-related neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. We report a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of more than seven days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematologic services at our hospital, as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs without prophylaxis; P=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs 79.5% in the colistin group; P=0.07), as determined by univariate analysis. This result was confirmed through multivariate analysis (OR: 0.475, 95%CI: 0.236-0.958; P=0.041). The prophylactic agents did not differ with regard to the microbiological findings (P=0.6, not significant). Of note, the use of ciprofloxacin was significantly associated with an increased rate of infections with pathogens that are resistant to the antibiotic used for prophylaxis (79.5% vs 9.5% in the colistin group; P<0.0001). The risk factors for higher infection rates were the presence of a central venous catheter (P<0.0001), mucositis grade III/IV (P=0.0039), and induction/relapse courses (vs consolidation; P<0.0001). In conclusion, ciprofloxacin prophylaxis appears to be of particular benefit during induction and relapse chemotherapy for acute myeloid leukemia. To prevent and control drug resistance, it may be safely replaced by colistin during consolidation cycles of acute myeloid leukemia therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Bacterial Infections; Central Venous Catheters; Ciprofloxacin; Cohort Studies; Colistin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucositis; Neutropenia; Retrospective Studies; Young Adult

Recent findings have identified Escherichia coli strains that are pan-β-lactam susceptible (PBL-S) but piperacillin-tazobactam resistant (TZP-R) in vitro We assessed the in vivo significance of this resistance profile in a neutropenic murine pneumonia model using humanized exposures of TZP with 18 clinical E. coli isolates, 8 TZP-S/PBL-S and 10 genotypically confirmed TZP-R/PBL-S. Despite phenotypically and genotypically defined resistance, TZP displayed efficacy against these isolates. Additional studies are required to define the clinical implications of these TZP-R/PBL-S strains.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Colistin; Culture Media; Disease Models, Animal; Drug Administration Schedule; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tobramycin; Treatment Outcome

Recent meta-analyses showed that antibiotic prophylaxis in patients with neutropenia after chemotherapy reduced the incidence of fever and mortality rate. Fluoroquinolones appear to be most effective and well tolerated. Thus, in April 2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin (COT/COL) to the fluoroquinolone ciprofloxacin (CIP) in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to compare efficacy and development of bacterial resistance with two different prophylaxis regimens over a time period of more than 4 years.. Induction chemotherapy courses given for AML during the antibiotic prophylaxis period with COT/COL (01/2006-04/2008) and CIP (04/2008-06/2010) were retrospectively analyzed with a standard questionnaire.. Eighty-five courses in the COT/COL group and 105 in the CIP group were analyzed. The incidence of fever was not significantly different (COT/COL 80 % vs CIP 77 %; p = 0.724). Also, the rate of microbiologically documented infections was nearly the same (29 vs 26 %; p = 0.625). In addition, there was no significant difference in the incidence of clinically documented infections (11 vs 19 %; p = 0.155) or in the rates of detected gram-positive and gram-negative bacteria. Of note, there was no increase in resistance rates or cases with Clostridium difficile-associated diarrhea in the CIP group.. The antibiotic prophylaxis with CIP compared to COT/COL in AML was similarly effective with no increase in bacterial resistance. COT/COL may have the advantages of providing additional prophylaxis against Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional option for treatment of febrile neutropenia.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Bacterial Infections; Ciprofloxacin; Clostridioides difficile; Colistin; Diarrhea; Drug Resistance, Bacterial; Enterocolitis, Pseudomembranous; Female; Fever; Fluoroquinolones; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

The prevalence of hospital strains of P. aeruginosa, A. baumannii and K. pneumoniae characterizing by multiple drug resistance to overwhelming majority of antibiotics anew evoked an increased interest to colistin. However, until now there is not enough information concerning pharmacokinetics of colistin to optimize dosage of this pharmaceutical. The study was carried out to analyze pharmacokinetics of both colistin and sodium colistimitate in children with chemically induced neutropenia. To quantitatively detect colistin in blood serum the technique of highly effective fluid chromatography with mass spectrometry was applied. The concentration of colistin was detected in 21 children with chemically induced neutropenia (13 patients with septicemia, 8 children of control group) after intravenous injection of sodium colistimitate. The significant variability of pharmacokinetic parameters of colistin was established both in patients with septicemia and in control group. The technique of highly effective fluid chromatography with mass spectrometry can be applied for therapeutic medicinal monitoring and optimization regimen of dosage.

Topics: Adolescent; Child; Child, Preschool; Colistin; Drug Resistance, Microbial; Female; Humans; Klebsiella pneumoniae; Male; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

A 66-year-old male with acute type adult T-cell leukemia that was refractory to chemotherapy underwent unrelated allogeneic bone marrow transplantation after non-myeloablative conditioning with fludarabine, busulfan and total body irradiation. During an episode of neutropenia on day 12 after transplantation, pneumonia and sepsis due to multi-drug resistant Pseudomonas aeruginosa developed. Drug susceptibility tests demonstrated resistance to all kinds of intravenous antibiotics available for P. aeruginosa in Japan. Multi-drug susceptibility tests by the breakpoint-checkerboard plate method were then performed and combination therapy with meropenem hydrate and colistin was started based on the test results. After starting treatment, clinical symptoms and laboratory data immediately improved and engraftment of neutrophils was achieved on day 18. Infections with multi-drug-resistant P. aeruginosa are often critical for patients after hematopoietic stem cell transplantation and are difficult to control. In this paper, we report a case of severe multi-drug-resistant P. aeruginosa infection that was successfully treated by combination therapy selected using the breakpoint-checkerboard plate method.

Topics: Aged; Anti-Bacterial Agents; Bone Marrow Transplantation; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Transplantation, Homologous; Treatment Outcome

Colistin is increasingly used as last-line therapy against Gram-negative pathogens. The pharmacokinetic (PK)/pharmacodynamic (PD) index that best correlates with the efficacy of colistin remains undefined. The activity of colistin against three strains of Pseudomonas aeruginosa was studied in neutropenic mouse thigh and lung infection models. The PKs of unbound colistin were determined from single-dose PK studies together with extensive plasma protein binding analyses. Dose-fractionation studies were conducted over 24 h with a dose range of 5 to 160 mg/kg of body weight/day. The bacterial burden in the thigh or lung was measured at 24 h after the initiation of treatment. Relationships between antibacterial effect and measures of exposure to unbound (f) colistin (area under the concentration-time curve [fAUC/MIC], maximum concentration of drug in plasma [fC(max)]/MIC, and the time that the concentration in plasma is greater than the MIC [fT > MIC]) were examined by using an inhibitory sigmoid maximum-effect model. Nonlinearity in the PKs of colistin, including its plasma protein binding, was observed. The PK/PD index that correlated best with its efficacy was fAUC/MIC in both the thigh infection model (R(2) = 87%) and the lung infection model (R(2) = 89%). The fAUC/MIC targets required to achieve 1-log and 2-log kill against the three strains were 15.6 to 22.8 and 27.6 to 36.1, respectively, in the thigh infection model, while the corresponding values were 12.2 to 16.7 and 36.9 to 45.9 in the lung infection model. The findings of this in vivo study indicate the importance of achieving adequate time-averaged exposure to colistin. The results will facilitate efforts to define the more rational design of dosage regimens for humans.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Colistin; Disease Models, Animal; Female; Humans; Lung; Lung Diseases; Mice; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Specific Pathogen-Free Organisms; Thigh

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin+rifampicin and imipenem+rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem+rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem+rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Immunosuppression Therapy; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Pneumonia, Bacterial; Rifampin; Treatment Outcome

Guidelines advocate >7d of broad-spectrum antibiotics for unexplained fever (UF) during neutropaenia. However, effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. This study evaluates the safety of discontinuing empirical broad-spectrum antibiotics if no microbial source is documented after an initial work-up of 72 h.. Prospective observational study at a tertiary-care haematology-unit in patients suffering from haematologic malignancies and treatment-induced prolonged neutropaenia of 10d. Oral fluoroquinolone and fluconazole prophylaxis was given from day 1. Fever was empirically treated with imipenem which was discontinued after 72 h if, following a standardised protocol, no infectious aetiology was documented. Duration of fever, antimicrobial therapy and overall mortality were registered.. One hundred and sixty six patients were evaluated during 276 neutropaenic episodes. One hundred and thirty six patients (82.5%) experienced 1 febrile episode. A total of 317 febrile episodes were observed, of which 177 (56%) were diagnosed as UF. In 135 febrile episodes (43%), a probable/definite infectious origin was documented. Mean duration of fever in neutropaenic periods with 1 febrile episode was 5d, and mean time of treatment with imipenem was 4.7d. In patients without documented infection, mean time of imipenem treatment was only 3.7d. Overall mortality 30 d after neutrophil recovery was 3.6% (6/166); no patient died from untreated bacterial infection.. Discontinuation of broad-spectrum antibiotics during neutropaenia in haematology patients on fluoroquinolone and fluconazole prophylaxis is safe, provided that no infectious aetiology is established after 72 h.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Colistin; Drug Therapy, Combination; Female; Fever of Unknown Origin; Fluconazole; Fluoroquinolones; Hematologic Neoplasms; Humans; Imipenem; Male; Middle Aged; Neutropenia; Prospective Studies; Withholding Treatment; Young Adult

MSI-78 is a 22 amino acid amphipathic peptide with potent antimicrobial activity against Gram-positive and Gram-negative organisms, including antibiotic-resistant strains. In this study, we assessed the in vitro activity of MSI-78 alone and in combination with eight clinically used antimicrobial agents against several strains of Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli isolated from blood of neutropenic febrile patients. Antimicrobial activity of MSI-78 was measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill studies and checkerboard titration method. The Gram-negative isolates were susceptible to the peptide at concentrations in the range 0.50-16 mg/L, while staphylococci showed lower susceptibility. MSI-78 demonstrated a higher antimicrobial activity than colistin against Gram-negative organisms. The checkerboard titration method demonstrated synergy when the peptide was combined with beta-lactams. These results provide evidence for the potential use of MSI-78 in the management of severe infections in neutropenic patients.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacteremia; Bacteria; beta-Lactams; Colistin; Colony Count, Microbial; Drug Therapy, Combination; Escherichia coli; Humans; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Staphylococcus aureus; Staphylococcus epidermidis

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination

The first 25 BMTs at the Royal Liverpool Children's Hospital (Alder Hey) were performed between April 1987 and July 1991. The aim of this report is to evaluate selective decontamination of the digestive tract (SDD) during the first post-BMT month in this series of 14 allografts and 11 autografts. SDD is a method used to abolish carriage of potentially pathogenic microorganisms including yeasts, Staphylococcus aureus and Gram-negative bacilli (GNB). Chlorhexidine mouth wash was used to decontaminate the oropharynx, and neomycin, colistin (polymyxin E) and nystatin (NEOCON) were given to eradicate gut carriage. Oropharyngeal decontamination was successful in 48% of patients, gut carriage was abolished in 60%, and eradication of the carrier state at both sites was achieved in 33%. A septic response was seen in 76% of children and 36% developed septicaemia (indigenous Gram-positive cocci only). A low carriage index for the target microorganisms during the study manoeuvre of SDD was associated with negative blood cultures (p < 0.01). Acute GVHD occurred in 28% of allografts, but was seen in none of the successfully decontaminated children (p < 0.05). It is concluded that septicaemia from yeasts and GNB, but not the septic response, were successfully prevented by SDD.

Topics: Adolescent; Bone Marrow Transplantation; Carrier State; Child; Child, Preschool; Chlorhexidine; Colistin; Digestive System; Disease Susceptibility; Drug Therapy, Combination; England; Female; Graft vs Host Disease; Humans; Incidence; Infant; Male; Neomycin; Neutropenia; Nystatin; Premedication; Retrospective Studies; Sepsis; Survival Analysis

Thirty-four patients with haematological malignancies were studied to investigate the effect of empirical broad-spectrum antibiotic therapy (ceftazidime and gentamicin) on the gastro-intestinal flora. Twenty-five patients with acute myeloid leukaemia or post-autologous bone-marrow transplantation were given framycetin, nystatin and colistin (Fracon), and two patients with non-Hodgkin's Lymphoma were on co-trimoxazole, as long-term gut prophylaxis. Semi-quantitative microbiology was carried out on oropharyngeal swabs and quantitative microbiology on faecal specimens. The oropharyngeal flora consisted mainly of streptococci, coagulase-negative staphylococci and coryneforms, and was little affected by ceftazidime/gentamicin. A strain of Enterobacter cloacae resistant to ceftazidime and gentamicin colonized one patient, who later developed septicaemia. The faecal flora of patients on Fracon was dominated by enterococci; the few enterobacteria present were eliminated by ceftazidime/gentamicin. The anaerobic flora was absent in 15% of patients; in the remainder, it consisted mainly of Bacteroides spp., and was little affected by ceftazidime/gentamicin. The faecal flora of patients not on Fracon always contained anaerobes, and some strains of enterobacteria persisted throughout antibiotic treatment. None of the patients was colonized by Clostridium difficile or Pseudomonas aeruginosa. Broad-spectrum therapy with ceftazidime and gentamicin appeared to have little effect on the gastro-intestinal flora, except to encourage the overgrowth of enterococci and reduce the numbers of enterobacteria.

Topics: Ceftazidime; Colistin; Enterobacter; Feces; Gentamicins; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Neutropenia; Nystatin; Oropharynx; Risk Factors; Staphylococcus; Streptococcus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agranulocytosis; Ciprofloxacin; Colistin; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Agranulocytosis; Amikacin; Colistin; Drug Therapy, Combination; Fever; Humans; Kanamycin; Neutropenia; Sulfamethoxazole; Trimethoprim

Topics: Adult; Anemia, Aplastic; Colistin; Drug Therapy, Combination; Framycetin; Humans; Male; Neutropenia; Nystatin; Rectal Fistula; Rectum; Sterilization

Topics: Carbenicillin; Colistin; Ecthyma; Gentamicins; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Meningitis; Neutropenia; Pneumonia; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Uremia