Infections In Non-neutropenic Patients Research Articles

Early picc-line infections in non-neutropenic patients are mainly due to E. coli suggesting that third-generation cephalosporin may be used as a first-line antibiotic therapy

PurposeTo describe the rate of peripherally inserted central catheter (PICC) -associated bloodstream infections, and the pathogens involved. MethodsWe prospectively analyzed data collected from all adult patients with a PICC insertion in a hematology unit in a tertiary care center between January 1, 2017 and June 30, 2020. ResultsA total of 370 PICCs were inserted in 275 patients with hematological malignancies: 54 (15 %) confirmed cases of central-line associated bloodstream infection (CLABSI) were identified. Enterobacteria were the most frequent bacteria identified, involved in 35 % of CLABSIs. Group 1 enterobacteria bacteremia occurred a much shorter time after insertion (median time to CLABSI 16 days) than group 2 or group 3 enterobacteria (median time to CLABSI 64 days, p-value = 0.049). ConclusionAmong Gram-negative bacilli CLABSI among non-neutropenic patients, E. coli identification was the most frequent and occurred earlier after insertion, suggesting that third-generation cephalosporin may be used as a first-line antibiotic therapy for enterobacteria bacteremia among non-neutropenic patients.

Infections during Non-Neutropenic Episodes in Pediatric Cancer Patients-Results from a Prospective Study in Two Major Large European Cancer Centers.

Whereas the clinical approach in pediatric cancer patients with febrile neutropenia is well established, data on non-neutropenic infectious episodes are limited. We therefore prospectively collected over a period of 4 years of data on all infectious complications in children treated for acute lymphoblastic or myeloid leukemia (ALL or AML) and non-Hodgkin lymphoma (NHL) at two major pediatric cancer centers. Infections were categorized as fever of unknown origin (FUO), and microbiologically or clinically documented infections. A total of 210 patients (median age 6 years; 142 ALL, 23 AML, 38 NHL, 7 leukemia relapse) experienced a total of 776 infectious episodes (571 during neutropenia, 205 without neutropenia). The distribution of FUO, microbiologically and clinically documented infections, did not significantly differ between neutropenic and non-neutropenic episodes. In contrast to neutropenic patients, corticosteroids did not have an impact on the infectious risk in non-neutropenic children. All but one bloodstream infection in non-neutropenic patients were due to Gram-positive pathogens. Three patients died in the context of non-neutropenic infectious episodes (mortality 1.4%). Our results well help to inform clinical practice guidelines in pediatric non-neutropenic cancer patients presenting with fever, in their attempt to safely restrict broad-spectrum antibiotics and improve the quality of life by decreasing hospitalization.

Intensive care medicine research agenda on invasive fungal infection in critically ill patients.

To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenic patients in the ICU setting. A systematic review of the medical literature taking account of national and international guidelines and expert opinion. Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients. Approximately 80% of IFIs are due to Candida spp. and 0.3-19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1→3-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed.

Clinical Study of the Efficacy and Safety of Liposomal Amphotericin B for the Treatment of Fungal Infections in Non-neutropenic Patients

Clinical Study of the Efficacy and Safety of Liposomal Amphotericin B for the Treatment of Fungal Infections in Non-neutropenic Patients

Candida infections in non-neutropenic children after the neonatal period

There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non-neonatal, immunocompetent children is not recommended.

Clinical predictors of Pseudomonas aeruginosa bacteremia among Gram-negative bacterial infections in non-neutropenic patients with solid tumor

This study was performed to identify risk factors in Pseudomonas aeruginosa bacteremia among Gram-negative bacterial infections in non-neutropenic patients with solid tumor. A case-control study was performed to identify clinical predictors for P. aeruginosa bacteremia among non-neutropenic patients with Gram-negative bacteremia. Each case of P. aeruginosa bacteremia was matched to one or two controls with Escherichia coli, Klebsiella, Enterobacter or Citrobacter species in non-neutropenic patients with solid tumor. Seventy-eight patients with P. aeruginosa bacteremia were compared with 98 control patients who had other Gram-negative bacteremias. The most common types of cancer were biliary tract cancer (49/176, 27.8%) and hepatocellular carcinoma (38/176, 21.6%), followed by gastric and bladder cancer. Factors associated with development of P. aeruginosa bacteremia were the presence of lung cancer, percutaneous tubes, nosocomial exposure, an invasive procedure and previous antimicrobial therapy (all P < 0.05). Independent risk factors for P. aeruginosa bacteremia included the presence of lung cancer and previous antimicrobial therapy. In the subgroup analysis including 90 patients with community-onset bacteremia, the previous use of antimicrobial agents and presence of bladder cancer were independent factors significantly associated with P. aeruginosa bacteremia. Underlying lung cancer and previous antimicrobial treatment were significantly associated with P. aeruginosa bacteremia in non-neutropenic patients with solid tumor. P. aeruginosa should be considered as a probable cause of Gram-negative bacteremia in this patient group.

Gram-negative organisms predominate in Hickman line-related infections in non-neutropenic patients with hematological malignancies

Catheter-related blood stream infections (CRBSI) cause significant morbidity and mortality in patients with hematological malignancies. Previous studies have identified a predominance of gram-positive organisms causing CRBSI but they included both neutropenic and non-neutropenic patients with solid organ and hematological malignancies. The aim of our study was to evaluate the incidence and microbiological profile of CRBSIs in a specific cohort of patients with hematological malignancies in their non-neutropenic phase of illness. A detailed retrospective review was done from January 2003 to December 2005 on all patients with hematological malignancies who had double-lumen non-antibiotic impregnated tunneled CVCs (Hickman catheters) inserted in our hospital to identify those fulfilling our criteria for CRBSI episodes. Amongst 273 evaluable patients, 61 developed CRBSI on 70 occasions. In contrast to previous studies, there was a predominance of gram-negative infections (68%). The majority (73%) of initial CRBSI episodes required catheter removal within 7 days of onset. Vancomycin and cefepime was the most common initial antibiotic regimen used. This study highlights the predominance of gram-negative infections in our cohort of non-neutropenic patients with underlying hematological malignancies who had Hickman catheters whose lines were not salvageable in the majority of cases. Empiric monotherapy with an antimicrobial agent with broad spectrum gram-negative cover needs to be given upfront pending results of the nature and sensitivity of organisms identified.

Effect of Granulocyte-Monocyte Colony-Stimulating Factor Therapy on Leukocyte Function and Clearance of Serious Infection in Nonneutropenic Patients

Impaired leukocyte function in patients with serious infections may increase mortality. Granulocyte-monocyte colony-stimulating factor (GM-CSF) broadly activates peripheral monocytes and neutrophils. We performed a clinical trial of GM-CSF in septic, hemodynamically stable patients to see whether GM-CSF treatment improved leukocyte function and mortality. Randomized, unblinded, placebo-controlled, prospective study. A 600-bed academic tertiary care center with a 120-bed ICU census with a high proportion of immunocompromised, solid-organ transplant recipients. Forty adult patients with infections meeting the criteria for the systemic inflammatory response syndrome but without hemodynamic instability or shock. Patients with sepsis and a documented infection were randomized to a 72-h infusion of GM-CSF (125 microg/m2) or placebo. GM-CSF infusion caused the up-regulation of the beta2-integrin adhesion molecule CD11b and the appearance of the activated ("sticky" or "avid") form of the molecule on circulating neutrophils and monocytes. CD11b density and avidity increases in response to the administration of tumor necrosis factor-alpha were blunted prior to treatment in these patients with serious infection. GM-CSF partially repaired this blunted response on both monocytes and neutrophils. It also caused the down-regulation of the adhesion molecule L-selectin on neutrophils and the up-regulation of human leukocyte antigen on monocytes. These changes were consistent with a broad activation of the circulating leukocyte pool. Although mortality and organ failure scores were similar in both groups, infection resolved significantly more often in patients receiving GM-CSF. GM-CSF infusion up-regulated the functional markers of inflammation on circulating neutrophils and monocytes and was associated with both the clinical and microbiological resolution of infection. There was no detectable exacerbation of sepsis-related organ failure or other deleterious side effects with the administration of this proinflammatory agent to patients with serious infections.

Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients. Paul-Ehrlich Society for Chemotherapy, Divisions of Mycology and Pneumonia Research.

To determine the epidemiological and clinical significance of invasive fungal infections in non-neutropenic patients in intensive care who stay longer than 10 days on the intensive care unit (ICU). Prospective epidemiological multicenter study over a period of 11 months, based on strict clinical, bacteriological, serological and histological criteria. Six surgical and two medical ICUs units in five university and two municipal hospitals. 435 non-neutropenic patients from medical and surgical ICUs with an ICU stay of more than 10 days. A new occurrence of invasive mycosis (3 sepsis/4 peritonitis/1 disseminated candidiasis), corresponding to the protocol conditions with onset after day 10 in the ICU, was detectable in 2.0% (95% confidence interval 0.85 to 3.8%) of the 409 patients who could be assessed. Candida species were identified as an infection-relevant pathogen in all cases. The most important risk factor for the development of an invasive mycosis was the onset of peritonitis by the day 11 in the ICU (odds ratio 11.3; p = 0.003). A fungal colonization was detected in 64% of patients (Candida species 56%, Aspergillus 4%, and other fungi). Six of 8 patients with an invasive mycosis died on the ICU; ICU mortality in patients with fungal colonization was 31% and in noncolonized patients 26%. Serological tests were not helpful clinically. The sensitivity was 88% for the Candida HAT (haemagglutination test) (threshold titer > 1:160), 100% for the Candida IFT (immunofluorescence test) (threshold titer > 1:80), and 50% for the Candida Antigen Test (Candtec Ramco, threshold titer > or = 1:8), and the specificity was 26, 6, and 73%, respectively. The specificity for the Aspergillus HAT (threshold titer > 1:10) was 29%. Invasive mycoses are rare in non-neutropenic ICU patients, even after a longer stay in the intensive care unit; fungal colonization, on the other hand, is frequently detectable. The mortality of invasive mycosis--even with systemic antimycotic therapy--was high; the mortality in patients with fungal colonization was not significantly increased compared to that in noncolonized patients. The serological test procedures, Candida HAT, Candida IFT, and the Candida Ramco Antigen Test, had a low specificity and were not helpful in diagnosing relevant invasive mycosis.

Ex vivo neutrophil function in response to three different doses of glycosylated rHuG-CSF (Lenograstim).

Granulocyte colony-stimulating factor (G-CSF) is being considered as adjuvant treatment for infections in non-neutropenic patients. Normal healthy donors were given rHuG-CSF (Lenograstim) at 2.5, 5.0 and 7.5 micrograms/kg subcutaneously daily for 5 d. Polymorphonuclear leucocyte (PMN) function tests were carried out on peripheral blood PMN before the first injection and at 24 h and 96 h. Circulating PMN levels were also measured at these time intervals and found to be significantly increased with all doses by 24 and 96 h. Investigation of cell surface antigen expression revealed no changes in beta 2 integrin (CD11b/ CD18) expression. L-selectin (CD62L) expression was reduced with all doses by 96 h, this being significant with the 7.5 micrograms/kg dose. Fc gamma RI (CD64) levels were significantly up-regulated with the 7.5 micrograms/kg dose by 96 h whereas Fc gamma RIII (CD16) expression was found to be reduced during G-CSF treatment. Superoxide anion production was significantly increased in response to N-formylmethionyl-leucylphenylalanine (FMLP) and opsonized Staphylococcus epidermidis stimulation at 24 h and 96 h with the 5.0 and 7.5 micrograms/kg doses. The initial rate of phagocytosis (0-2 min) appeared to have increased with the 7.5 and 5.0 micrograms/kg doses at 96 and 24 h compared with PMN responses pretreatment, although these increases were not statistically significant. These results show that G-CSF enhances the functional responses of PMN stimulated by physiological agnonists and may help in the treatment of infections.

Timing of treatment for nonneutropenic patients colonized with Candida

There has been a continuing evolution of the clinical spectrum of Candida infection in nonneutropenic patients. With better understanding of the predisposing factors for fungemia in critically ill patients, interest now centers on indications for early therapy, prior to the progression of colonization to fungemia. Recent prospective trials have identified persistence of Candida species in repetitive cultures of various sites as an essential if not necessary precursor for fungemia. Treatment for patients requiring prolonged intensive-care-unit residence and demonstrating colonization with Candida is suggested, based on the frequency with which such patients progress to fungemia. The efficacy of such treatment is undocumented, and clinical trials of various regimens of polyene or azole antifungals is needed.

Investigation of the sequence of colonization and candidemia in nonneutropenic patients

Among neutropenic patients with hematologic malignancies, candidemia has been shown to arise typically from autoinfection after colonization. In patients without neutropenia, we examined the similarities of strains colonizing or infecting various body sites and those subsequently causing Candida bloodstream infections. Strain similarity was examined by karyotyping and restriction endonuclease analysis of genomic DNA (REAG) by using two restriction enzymes (SfiI and BssHII). The banding patterns of 42 isolates from 19 patients were independently evaluated in a blinded fashion by three observers. The interobserver reliability measured with a generalized kappa statistic was 0.59 for karyotyping, 0.84 for REAG with SfiI, and 0.88 for REAG with BssHII (P < 0.001 for each). REAG classified the initial colonizing or infecting isolate and subsequent blood isolates as identical in 16 patients (84%). The mean duration of colonization or infection prior to a positive blood culture was 5 and 23 days in patients infected with related and unrelated isolates, respectively (P = 0.14; 95% confidence interval = -14.5 to 50.5). Karyotyping results matched the REAG results for isolates from 14 of the 19 patients (74%). In patients infected with identical isolates, the initial isolate was most frequently recovered from the urine (n = 5) or vascular catheter tips (n = 4). In the five subjects with organisms showing disparate results between the methods, karyotyping revealed different banding patterns, whereas REAG suggested that the isolates were identical. Candida colonization or infection with an identical strain frequently precedes bloodstream infection in nonneutropenic patients. Future studies should evaluate whether patients at high risk for candidemia and who have vascular catheter or urine samples that are positive for a Candida on culture should be treated empirically.

Haemopoietic growth factors in the treatment of infection in non-neutropenic patients.

Haemopoietic growth factors in the treatment of infection in non-neutropenic patients.

Current strategies for treating invasive candidiasis: emphasis on infections in nonneutropenic patients.

The increasing incidence of nosocomial candidal infections is a pivotal problem for patients who do not have neutropenia. In contrast with previous principles, candidemia--even in nonneutropenic patients--should be treated with systemic antifungal agents except in rare circumstances. Amphotericin B remains the agent of choice for treatment of hematogenously disseminated candidiasis and for candidemia, although the optimal dosage and duration of this therapy are poorly defined. Therapy with fluconazole is an alternative for patients who are intolerant to amphotericin B; the efficacy of fluconazole compared with that of amphotericin B in hematogenous candidal infections is unknown but is currently being evaluated. Removal of prosthetic devices that are infected with Candida is necessary in nearly all instances to cure the infection. Similarly, removal of an indwelling catheter whose use is associated with candidemia, as opposed to leaving the catheter in place during antifungal therapy, may increase survival rates of patients and lower their rates of complication. Antifungal prophylaxis may be useful for patients who are undergoing transplantation of an organ.

Cefsulodin and ceftazidime, two antipseudomonal cephalosporins

The microbiologic, pharmacokinetic, and clinical profiles of cefsulodin and ceftazidime are reviewed. Ceftazidime is a broad-spectrum beta-lactamase stable cephalosporin with excellent activity against gram-negative bacilli, including Pseudomonas aeruginosa. Cefsulodin is a narrow-spectrum cephalosporin with activity against Staphylococcus aureus and Ps. aeruginosa. Both antibiotics, which are expected to be marketed in the United States, are superior to currently available cephalosporins against Ps. aeruginosa. Cefsulodin and ceftazidime are administered by the i.m. or i.v. route, are widely distributed in body fluids and tissues, and exhibit relatively low binding to serum proteins. They are eliminated primarily through the urine, and they generally can be administered every 8 to 12 hours, depending upon the type of infection. Cefsulodin has been used successfully in the treatment of various Ps. aeruginosa infections in noncomparative studies. Ceftazidime has been successfully used as a single agent in comparative studies for Ps. aeruginosa infections. Because of its broad spectrum and its activity against penicillin-resistant and aminoglycoside-resistant Pseudomonas, ceftazidime can be used empirically as a single agent in place of combination therapy in patients with cystic fibrosis. Ceftazidime has also been useful as a single agent used empirically for treating febrile episodes in neutropenic patients and for treating hospital-acquired infections in nonneutropenic patients when Pseudomonas cannot be ruled out. Ceftazidime is a useful broad-spectrum antibiotic, particularly in the empiric therapy of nosocomial infections and in patients whose underlying conditions predispose them to Ps. aeruginosa infections. Cefsulodin may prove useful as single-agent therapy of certain infections known to be caused by Ps. aeruginosa, but its empiric use is not encouraged.