Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ninety-nine patients with 101 bacteraemic episodes due to Pseudomonas aeruginosa (PA) within 6 years were divided into two groups according to their resistance to imipenem; of these 91 episodes were due to imipenem-sensitive (ISPA) and 10 due to imipenem-resistant (IRPA) strains. Risk factors, clinical course and outcome were evaluated and compared in the two groups. Acute leukaemia, long-lasting neutropenia, previous therapy with amikacin, third-generation cephalosporins, imipenem and prophylaxis with quinolones were significantly more frequently associated with IRPA than with ISPA. Imipenem-resistant PA bactereamias were associated with a higher incidence of septic shock (40% vs 19.8%) p. 161 0.02) and death 33.3%) than were ISPA bacteraemias. Since 1992, when first IRPA appeared, the incidence of imipenem-resistance increased tenfold, and in 1994, up to 10% of the PA populations causing bloodstream infections in cancer patients in our centre were imipenem-resistant.
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PMID:Imipenen-resistant Ps. aeruginosa bacteraemia in cancer patients: risk factors, clinical features and outcome. 906 55

Ninety nine patients with 101 bacteraemic episodes due to Ps. aeruginosa (PA) within 6 years were divided into two groups according to their resistance to imipenem-91 due to imipenem sensitive (ISPA) and 10 due to resistant (IRPA). Risk factors, the clinical course and the outcome were evaluated and compared. Acute leukaemia, prolonged neutropenia, previous therapy with amikacin, third generation of cephalosporins, imipenem and prophylaxis by quinolones were significantly more frequently associated with IRPA. Imipenem resistant PA bacteraemia were associated with higher incidence of septic shock (40% vs 19.8%, p < 0.02) and death (33.3%) than ISPA bacteraemias. Since 1992, when first IRPA appeared, the incidence of imipenem resistance increased tenfold, and in 1994, up to 10% of PA causing bloodstream infections in cancer patients in our center were imipenem resistant. (Tab. 3, Ref. 8.).
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PMID:Imipenem-resistant Ps. aeruginosa bacteraemia in cancer patients: risk factors, clinical features and outcome. 911 27

Imipenem plus cilastatin is a beta-lactam antibiotic with a broad spectrum and good tolerance. For this its use is indicated in serious infections even in children. The authors carried out a preliminary bacteriological study in patients affected by serious infection, cystic fibrosis, tumors, neutropenia, subjects undergoing intensive therapy and those with abdominal surgical infection. Isolated microorganism sensitivity in these patients, towards imipenem was very high (89%-100%). With these premises, 35 patients with serious infections in various locations were treated only with imipenem. Of these, 15 were oncologic neutropenic and 20 normal. In the first group therapeutic success was 66.6% and in the second one 80%. Local and systemic tolerance always showed good results.
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PMID:Imipenem use in serious childhood infections. 1204 69

Resistance patterns that are currently problematic in Europe can vary greatly within the same species over time, among various patient populations and among geographic regions on the same continent. The results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program, which monitors carbapenem resistance rates in institutions using meropenem, were used to determine resistance differences among Proteus mirabilis. MIC results from 688 P. mirabilis strains were classified into 4 patient care groups: ICU (n=426), neutropenia patients (NP; n=145), general wards (n=97) and cystic fibrosis patients (CF; n=20). A total of 40 centers from 12 European countries have participated since 1997, divided into 3 geographic regions (East, North, South). All testing was performed by NCCLS reference methods and interpretive criteria, including screening of extended-spectrum beta-lactamase (ESBL) phenotypes. Over the monitored interval the resistance rates varied for each agent without a clear trend toward a greater rate. Rank order of susceptibility was: meropenem (99%) > piperacillin/tazobactam (TAZ; 96%) > cefepime (95%) > ceftazidime (CAZ; 94%) > imipenem (IPM; 92%). Ciprofloxacin (CIP) was the least active agent tested (MIC90 4 microg/ml; 86% susceptible). Unexpectedly, 3.6% of P. mirabilis were imipenem-resistant (MIC, > or = 16 microg/ml). Greater rates of resistance were found for strains from NP and CF patients, and from eastern or southern European sites, usually associated with epidemic clusters. Generally susceptible species such as P. mirabilis have recently emerged as therapeutic problems in European medical centers following mutations that compromise CIP, CAZ and aminoglycoside use. Imipenem also showed decreased susceptibility of greater than 7% compared to less than 1% for meropenem. Continued surveillance by the MYSTIC Program appears to be a prudent practice to focus effective empiric treatment regimens.
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PMID:Emerging antimicrobial resistances among Proteus mirabilis in Europe: report from the MYSTIC Program (1997-2001). Meropenem Yearly Susceptibility Test Information Collection. 1212 Aug 79

A total of 67 patients with diseases of the blood system and infectious complications, admitted to the Hematological Department of the Novosibirsk Regional Clinical Hospital, were examined. For this study only patients with etiologically established diagnosis were taken. The study revealed that Pseudomonas sp., whose strains were susceptible to Ceftazidime in 100% of cases and resistant to Cefepime and Imipenem in 15-17% of cases, was the etiological agent of 13.6% of all cases of infectious complications in hemoblastosis patients. Infectious lesions of pulmonary parenchyma, the presence of chronic diseases of the respiratory tract in the medical history, neutropenia, artificial ventilation of the lungs were found to be adverse prognostic factors with respect to a high risk of Pseudomonas infection in such patients. Therapy with glucocorticosteroids and cytostatics, preceding antibacterial prophylaxis were not linked with the isolation of Pseudomonas from the patients exhibiting the same levels of lethality and severity of infectious complications.
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PMID:[Risk factors of pseudomonas infection in hemoblastosis patients]. 1548 20

Imipenem, the first carbapenem discovered, was developed more than two decades ago in response to an unmet need for a highly potent, broad-spectrum antimicrobial agent with a strong safety profile. It has since been used to treat more than 26 million patients. In an era where antibiotic use has driven antibiotic resistance, choosing appropriate initial therapy for serious infection is critical. Appropriate antibiotic regimens must cover all likely pathogens, be administered promptly at the correct dosage and dosing interval, be well tolerated and prevent the emergence of resistance. While imipenem was initially reserved for use in intractable, serious infections, the benefits of early aggressive therapy are now known, making imipenem a core agent in de-escalation therapy due to proven efficacy and safety for indications such as nosocomial pneumonia, intra-abdominal infection, sepsis and febrile neutropenia. De-escalation therapy with an agent such as imipenem minimizes resistance development by initiating aggressive initial treatment and then tailoring therapy based on patient response and culture results, switching to a less expensive, narrower spectrum antibiotic regimen or shortening the duration of therapy. Imipenem has maintained sustained clinical efficacy, tolerability and in vitro activity against important bacterial pathogens for two decades. We review the factors that continue to make imipenem as appropriate an agent for de-escalation therapy now as it was 20 years ago.
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PMID:Two decades of imipenem therapy. 1699 45

The carbapenems are beta-lactam antimicrobial agents with an exceptionally broad spectrum of activity. Older carbapenems, such as imipenem, were often susceptible to degradation by the enzyme dehydropeptidase-1 (DHP-1) located in renal tubules and required co-administration with a DHP-1 inhibitor such as cilastatin. Later additions to the class such as meropenem, ertapenem and doripenem demonstrated increased stability to DHP-1 and are administered without a DHP-1 inhibitor. Like all beta-lactam antimicrobial agents, carbapenems act by inhibiting bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). Carbapenems are stable to most beta-lactamases including AmpC beta-lactamases and extended-spectrum beta-lactamases. Resistance to carbapenems develops when bacteria acquire or develop structural changes within their PBPs, when they acquire metallo-beta-lactamases that are capable of rapidly degrading carbapenems, or when changes in membrane permeability arise as a result of loss of specific outer membrane porins. Carbapenems (imipenem, meropenem, doripenem) possess broad-spectrum in vitro activity, which includes activity against many Gram-positive, Gram-negative and anaerobic bacteria; carbapenems lack activity against Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Stenotrophomonas maltophilia. Compared with imipenem, meropenem and doripenem, the spectrum of activity of ertapenem is more limited primarily because it lacks activity against Pseudomonas aeruginosa and Enterococcus spp. Imipenem, meropenem and doripenem have in vivo half lives of approximately 1 hour, while ertapenem has a half-life of approximately 4 hours making it suitable for once-daily administration. As with other beta-lactam antimicrobial agents, the most important pharmacodynamic parameter predicting in vivo efficacy is the time that the plasma drug concentration is maintained above the minimum inhibitory concentration (T>MIC). Imipenem/cilastatin and meropenem have been studied in comparative clinical trials establishing their efficacy in the treatment of a variety of infections including complicated intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia, complicated urinary tract infections, meningitis (meropenem only) and febrile neutropenia. The current role for imipenem/cilastatin and meropenem in therapy remains for use in moderate to severe nosocomial and polymicrobial infections. The unique antimicrobial spectrum and pharmacokinetic properties of ertapenem make it more suited to treatment of community-acquired infections and outpatient intravenous antimicrobial therapy than for the treatment of nosocomial infections. Doripenem is a promising new carbapenem with similar properties to those of meropenem, although it appears to have more potent in vitro activity against P. aeruginosa than meropenem. Clinical trials are required to establish the efficacy and safety of doripenem in moderate to severe infections, including nosocomial infections.
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PMID:Comparative review of the carbapenems. 1748 46

To determine treatment outcome using ceftazidime-aminoglycosides in febrile neutropenic children with cancer, the authors conducted a prospective cohort study in 216 episodes. Early and complete responses to antibiotics were 108/216 (50.0%) and 133/216 (61.6%) episodes, respectively. Death, a modification of antibiotic(s), and resistance to ceftazidime were 2/118 (1.7%), 73/216 (33.8%), and 4/216 (1.9%) episodes, respectively. Primary bacteremia and emerging bacteremia during treatment were 20/216 (9.3%) and 5/216 (2.3%) episodes. Ceftazidime-aminoglycosides was found to be a reasonable initial treatment of febrile neutropenia in the authors' institution. Imipenem is considered in patients who have clinical sepsis and who fail to respond to initial treatment.
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PMID:Clinical outcome of febrile neutropenia in children with cancer using ceftazidime and aminoglycosides. 1809 50

Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion abnormalities predispose to septic shock and increased mortality in neutropenic setting. We aimed at determining predictors of severe sepsis in neutropenic patients. Between 1 October and 31 December 2007, 41 patients (21 with acute myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem cell transplantation for a mantle cell lymphoma) with chemotherapy-induced neutropenia (<0.5 x 10(9)/l) lasting for more than 7 days were included in this study. The median age was 28 years (range: 3-58 years). All patients were on oral antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B) prophylaxis. The first neutropenic febrile episode was treated with piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h from the start of this first line of treatment, amphotericin B i.v. is added. Imipenem was introduced in the case of non-response and finally glycopeptides were introduced according to the IDSA criteria. Severe sepsis and septic shock are defined according to the criteria of the consensus conference of the ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic. Ninety-four febrile episodes were observed: 27 microbiologically documented (28.7%), six clinically documented (6.3%) and 61 fever of unknown origin (65%). Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram-positive organisms and three combined (Gram+ and -). Clinically documented infections were pneumonia (two), neutropenic enterocolitis (one), sinuses infection (one) and cutaneous infection (two). Severe sepsis accounted for 22 febrile episodes. Factors associated with the occurrence of severe sepsis were: hypophosphatemia (<0.8 mmol/l; p=0.05, OR=3.9, 95% CI: 1.3-45.7), hypoproteinemia (<62 g/l; p=0.006, OR=4.1, 95% CI: 1.4-11.4) and non-adapted antibiotherapy at the onset of severe sepsis (p=0.019, OR=2.7, 95% CI: 1.02-7.39). However, heart rate/systolic blood pressure ratio <1.1 (p<0.001, OR=0.1, 95% CI: 0.03-0.31) and Creactive protein <80 mg (p=0.001, OR=0.14, 95% CI: 0.04-0.54) were not predictive.
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PMID:Factors associated with severe sepsis: prospective study of 94 neutropenic febrile episodes. 2013 59


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