The Dutch Working Party on Antibiotic Policy (SWAB) Recommendations for the Diagnosis and Management of Febrile Neutropenia in Patients with Cancer.

INTRODUCTION: This guideline was written by a multidisciplinary committee with mandated members of the Dutch Society for Infectious Diseases, Dutch Society for Hematology, Dutch Society for Medical Oncology, Dutch Association of Hospital Pharmacists, Dutch Society for Medical Microbiology, and Dutch Society for Pediatrics. The guideline is written for adults and pediatric patients. METHOD: The recommendations are based on the answers to nine questions formulated by the guideline committee. To provide evidence-based recommendations we used all relevant clinical guidelines published since 2010 as a source, supplemented with systematic searches and evaluation of the recent literature (2010-2020) and, where necessary, supplemented by expert-based advice. RESULTS: For adults the guideline distinguishes between high- and standard-risk neutropenia based on expected duration of neutropenia (> 7 days versus ≤ 7 days). Where possible a distinction has been made between pediatric and adult patients. CONCLUSION: This guideline was written to aid diagnosis and management of patients with febrile neutropenia due to chemotherapy in the Netherlands. The guideline provides recommendation for children and adults. Adults patient are subdivided as having a standard- or high-risk neutropenic episode based on estimated duration of neutropenia. The most important recommendations are as follows. In adults with high-risk neutropenia (duration of neutropenia > 7 days) and in children with neutropenia, ceftazidime, cefepime, and piperacillin-tazobactam are all first-choice options for empirical antibiotic therapy in case of fever. In adults with standard-risk neutropenia (duration of neutropenia ≤ 7 days) the MASCC score can be used to assess the individual risk of infectious complications. For patients with a low risk of infectious complications (high MASCC score) oral antibiotic therapy in an outpatient setting is recommended. For patients with a high risk of infectious complications (low MASCC score) antibiotic therapy per protocol sepsis of unknown origin is recommended.

Hairy cell leukemia presenting with Ecthyma Gangrenosum- a case report.

BACKGROUND: Ecthyma gangrenosum is a cutaneous infectious usually associated with P. aeruginosa. It usually develops In patients with an underlying immunodeficiency. CASE PRESENTATION: A 50-year old mentally disabled white male with a history of epilepsy presented with fever and a painless red macule on his right arm which rapidly progressed to a painful ulcer. Blood and lesion cultures revealed P.aeruginosa, confirming our clinical diagnosis of ecthyma gangrenosum. Subsequently an underlying immune deficit was found, namely patient was diagnosed with hairy-cell leukemia. Despite adequate antibiotics no infection control could be achieved. After treating the underlying immune deficit as well, the infection and hairy-cell leukemia resolved completely. CONCLUSION: Ecthyma gangrenosum is an important cutaneous infection to recognize, because it is it is typically associated with P.aeruginosa bacteremia. Recognizing this skin leasion should prompt empiric antimicrobial therapy including an agent with antipseudomonal activity. Furthermore, just like in our case, the presence of ecthyma gangrenosum can signal the presence of an occult immune deficit, warranting further investigation.

Recommendations for the successful control of a large outbreak of vancomycin-resistant Enterococcus faecium in a non-endemic hospital setting.

BACKGROUND: A large outbreak of three epidemic vancomycin-resistant Enterococcus faecium (VRE) clones affected the study hospital for almost two years. AIM: To describe the strategy to successfully control this outbreak and eradicate VRE from the study hospital. METHODS: Infection control interventions started after detection of VRE in three patients. Hospital-wide surveillance was started after ongoing transmission despite isolation precautions, cleaning and contact tracing. Hygiene education and discipline were enhanced. Despite these interventions, additional measures were required to control the outbreak, such as ward disinfection with hydrogen peroxide vapour and the introduction of a VRE quarantine ward. Ultimately, ciprofloxacin prophylaxis for haematological patients on chemotherapy was abandoned. FINDINGS: Over a 22-month period, 242 VRE carriers were identified. Of these, 128 (53%) patients were detected by hospital-wide surveillance alone. Three epidemic clones were detected: ST494-vanA (N = 160), ST78-vanA (N = 23) and ST117-vanB (N = 32). In total, 5614 possible contacts were identified. VRE transmission occurred on 13 out of 23 wards. VRE was cultured from clinical specimens in 22 patients (seven with bacteraemia). Since January 2014, no further transmission of these VRE clones has been observed. CONCLUSION: Infection control measures according to international guidelines were insufficient to expose the outbreak to its full extent and control it. Its full extent only became apparent after sustained hospital-wide screening. Successful control of this hospital-wide VRE outbreak was feasible, but required great effort. Final containment and eradication of the epidemic clones was achieved by environmental decontamination with hydrogen peroxide vapour, strict isolation precautions, a VRE quarantine ward and antimicrobial stewardship.

Single-dose antibiotic prophylaxis for urinary catheter removal does not reduce the risk of urinary tract infection in surgical patients: a randomized double-blind placebo-controlled trial.

We conducted a double-blind, placebo-controlled randomized trial to assess the effect of single-dose prophylaxis using co-trimoxazole (960 mg) (n = 46) or ciprofloxacin (500 mg) (n = 43) vs. placebo (n = 51) before urinary catheter removal on significant bacteriuria (SBU) (primary outcome) and urinary tract infection (UTI) in surgical patients with scheduled bladder drainage for 3-14 days. SBU was determined directly after catheter removal, and UTI 12-14 days after catheter removal. After 12-14 days, incidences of SBU were 19%, 19% and 33% for patients receiving ciprofloxacin, co-trimoxazole and placebo, respectively (p ns), and incidences of UTI were 3%, 0% and 3% for patients receiving ciprofloxacin, co-trimoxazole and placebo, respectively (p ns).

Nocardiosis: a case series and a mini review of clinical and microbiological features.

Infections caused by Nocardia species are uncommon and have a wide variety of clinical manifestations in immunocompetent and immunocompromised patients. The diagnosis of nocardiosis can easily be missed because there are no characteristic symptoms. We present one case of a Nocardia infection in detail and give a brief description of eight other cases, including a relatively unique type of Nocardia veterana, diagnosed in our hospital during a five-year period. The diversity of clinical manifestations, microbiological identification and general principles of treatment of nocardiosis are reviewed.

Regional and seasonal differences in incidence and antibiotic resistance of Campylobacter from a nationwide surveillance study in The Netherlands: an overview of 2000-2004.

Campylobacter is the most common cause of bacterial gastroenteritis worldwide. This study describes regional and seasonal differences among culture-proven Campylobacter infections in The Netherlands in 2000-2004. Data were used from two ongoing projects in The Netherlands, covering 3 million and 8 million inhabitants, respectively, for surveillance of infectious diseases. The incidence of Campylobacter infection was highest in the south of The Netherlands (55.7/100,000 vs. an average of 39.1/100,000 in other regions). The incidence in urbanised areas was 41.9/100,000 vs. 32.4/100,000 in rural areas. High stable rates of resistance to fluoroquinolones (35%) were observed. Resistance to erythromycin increased from 1.9% (in 2001) to 2.7% (in 2004). The highest rates of resistance to erythromycin were found in the south. Resistance rates increased with increasing urbanisation, most obviously for fluoroquinolones (35.9% urban vs. 27.10% rural). An inverse relationship was observed between the incidence of infection (high in summer, low in winter) and resistance to both fluoroquinolones and macrolides. Resistance to fluoroquinolones was higher in travel-related infections (54%) than in endemic infections (33%). Differences in regional incidence and resistance rates of Campylobacter infections were found. Foreign travel appeared to be associated with higher resistance rates. Given the high fluoroquinolone resistance rate, empirical treatment of severe, microbiologically confirmed, Campylobacter infection with a fluoroquinolone should be discouraged, pending susceptibility testing.

[Delayed recognition of falciparum malaria from a non-endemic region in the Dominican Republic]. / Laat herkende malaria tropica uit een niet-endemisch gebied in de Dominicaanse Republiek.

A 28-year-old patient had suffered from fever, headache, abdominal pains and vomiting for the past three weeks. She had visited a region in the Dominican Republic where the risk of malaria is considered to be low. The complaints were initially regarded as a viral infection. Later, however, she was found to have severe falciparum malaria. She recovered completely following antibiotic therapy. Since November 2004, 17 cases of falciparum malaria have been reported world-wide among travellers to non-endemic regions in the Dominican Republic. Physicians should always consider the possibility of malaria in travellers because a timely diagnosis of falciparum malaria can be of vital importance.

Catheter replacement in continuous arteriovenous hemodiafiltration: the balance between infectious and mechanical complications.

OBJECTIVE: To assess the optimal moment of central vascular catheter replacement balancing infectious and mechanical complications in continuous renal replacement therapies in critically ill patients with acute renal failure. METHODS: Prospective sequential trial with historical controls to compare liberal catheter replacement when clinically indicated with routine catheter replacement every 5 days in consecutive patients treated by continuous arteriovenous hemodiafiltration in a level I secondary referral intensive care unit of a university-affiliated teaching hospital. Intention-to-treat analysis. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients underwent catheter replacement when clinically indicated (group II), and 21 patients served as historical controls (group I). The groups were comparable for sex, age, Acute Physiology and Chronic Health Evaluation II scores, comorbidity, and creatinin and urea levels at the start of continuous arteriovenous hemodiafiltration. In group I, 71 catheters were used for 346 treatment days, and in group II, 68 catheters were used for 495 treatment days. The mean duration of catheterization was 4.9 +/- 2.0 days vs. 7.3 +/- 4.5 days, respectively (Student's t-test p <.001). There was no significant difference between the incidence of colonization of catheters (46.8% in group I vs. 39.1% in group II; chi-square p =.35) In group I, bacteremia and catheter sepsis occurred in two patients, whereas this did not occur in group II. The occurrence of mechanical complications was comparable in both groups (15.5% in group I vs. 19.1% in group II). There were significantly more mechanical complications with arterial vs. venous catheters (17 vs. 7; chi-square p =.027). CONCLUSION: When catheters were changed as clinically indicated, they remained significantly longer in situ vs. being replaced routinely every 5 days; infectious and mechanical complications were comparable. The incidence of catheter sepsis was low (2.2%), and no prosthesis infection occurred. Catheter replacement when clinically indicated seems to be as safe as routine replacement every 5 days.

Strongyloides stercoralis infection: how to diagnose best?

Four patients are described with a Strongyloides stercoralis infection. Several techniques to diagnose this infection are discussed. The so-called Baermann method is emphasised. Especially in chronic infections the combination of serology and the Baermann method seems the best diagnostic approach. Treatment with albendazole or ivermectin are suggested treatments.

Conversion rate towards a syncytium-inducing (SI) phenotype during different stages of human immunodeficiency virus type 1 infection and prognostic value of SI phenotype for survival after AIDS diagnosis.

The presence of syncytium-inducing (SI) human immunodeficiency virus type 1 (HIV-1) variants is predictive for accelerated progression to AIDS. This study showed that a 4-year survival with AIDS also occurred significantly more often for patients who lacked SI variants. However, multivariate Cox analysis excluded the predictive value of SI viruses for rapid death as being independent from low CD4+ T cell counts. Incidence of appearance of SI variants was increased in persons with CD4+ T cell counts <500/microliter but remained constant in the strata of CD4+ T cell counts <500/microliter, excluding the possibility that loss of immune control is the only prerequisite for the development of SI HIV-1 variants.

Value of laboratory investigations in clinical suspicion of cytomegalovirus-induced upper gastrointestinal tract ulcerations in HIV-infected patients.

To assess the value of laboratory investigations for the diagnosis and treatment of cytomegalovirus-induced upper gastrointestinal tract ulcerations, the medical records and biopsy material from HIV-infected patients were reviewed retrospectively during a 12-month period. Clinical diagnosis of cytomegalovirus (CMV) ulceration, based on characteristic endoscopic appearance of extensive ulceration of the mid- to distal esophageal or gastric mucosa and responsiveness to anti-CMV therapy, was compared with laboratory investigations of biopsies. Laboratory procedures consisted of both histopathological examination of the biopsy specimens and viral culture. Twenty episodes in 12 HIV-infected patients could be evaluated. Clinical diagnosis of CMV ulceration appeared to be justified in 14 of 20 episodes (70%), which were confirmed by laboratory investigations. Of the remaining six episodes, which showed partial or no response to anti-CMV therapy, laboratory investigations were negative in two episodes and discrepant in four episodes (histopathology or viral culture positive). A good response to anti-CMV therapy was more frequent in patients whose biopsies proved positive by histopathological examination and/or viral culture than in patients with negative tests (82% versus 0%), which indicates the importance of both investigations. In conclusion, laboratory diagnosis of CMV-induced upper gastrointestinal tract ulcerations supported the diagnosis and decisions on treatment of CMV-induced upper gastrointestinal tract ulcerations.

Relation between changes in cellular load, evolution of viral phenotype, and the clonal composition of virus populations in the course of human immunodeficiency virus type 1 infection.

The relationship between the evolution of human immunodeficiency virus type 1 (HIV-1) biologic phenotype, changes in the proportion of infected peripheral blood mononuclear cells, and the relative contribution of non-syncytium-inducing (NSI) and syncytium-inducing (SI) HIV-1 variants to virus load was studied during the course of HIV-1 infection. In 65 HIV-1-infected subjects, the proportion of infected CD4 T cells was higher in persons who carried SI variants. Longitudinal studies revealed that the emergence of SI HIV-1 variants can occur at relatively low numbers of HIV-1-infected cells. Emergence of SI variants frequently coincided with an increase of virus load due to an expansion of both NSI and SI variants, although the contribution of SI viruses to the total virus population significantly increased with time after SI phenotype conversion. These data indicate that NSI to SI phenotype conversion, rather than resulting from high virus load, is part of the sequence of events that leads to increased virus load and CD4 cell depletion.

Temporal relationship between elongation of the HIV type 1 glycoprotein 120 V2 domain and the conversion toward a syncytium-inducing phenotype.

The second and third variable domains (V2 and V3) of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope molecule have been shown to be determinants of syncytium-inducing (SI) capacity. Previously we have reported evidence that increased length of the V2 domain and duplication or relocation of potential N-linked glycosylation sites in V2 might be used as prognostic markers for evolution toward an SI phenotype. Here, we used a PCR assay that discriminates a 6-nucleotide difference in the length of the V2 domain, with a sensitivity of 1 elongated V2 domain when present in a background of 125 to 625 short V2 domains. Analysis of DNA isolated directly from PBMCs from 11 HIV-1-infected individuals prior to SI phenotype conversion revealed, however, that the usefulness of this PCR for V2 length polymorphism as predictive marker for SI phenotype evolution is limited. The strong association as observed in our previous study between elongation of the V2 domain and an SI phenotype prompted us to expand our first analysis. An extremely significant correlation was observed between V2 length and virus phenotype for samples obtained at about the moment of SI conversion, but not for samples obtained 3 to 35 months after SI phenotype conversion, suggesting that changes in V2 may be only transiently required to allow SI phenotype evolution. This possibly only transient nature of V2 elongation may explain the discrepancy between results by our group and others.

T cell function in vitro is an independent progression marker for AIDS in human immunodeficiency virus-infected asymptomatic subjects.

The predictive value of low T cell reactivity to CD3 monoclonal antibodies for development of AIDS was evaluated and compared with low CD4+ cell numbers and the presence of syncytium-inducing human immunodeficiency virus (HIV) variants in 122 seropositive asymptomatic homosexual men for 4.5 years. Low T cell reactivity was a strong predictor for progression to AIDS in a multivariate proportional hazards analysis using these markers as covariates at entry and as time-dependent covariates. The combination of the three markers was associated with development of AIDS in 6 of 7 men within 15 months. In contrast, the group that lacked any of these markers had a very low risk (11%) for developing AIDS. In groups with one or two of these three markers, progression rates were 33% and 66%, respectively. These data demonstrate that measurement of T cell function in vitro is of value for staging of HIV infection and may be useful for monitoring therapy.

Immunologic and virologic markers determining progression to AIDS.

Infection with the human immunodeficiency virus type 1 (HIV-1) results in a severe immunodeficiency characterized by a depletion of CD4+ T-helper cells. Furthermore, it is well documented that in asymptomatic persons the number of CD4+ cells is also a good predictor of progression to AIDS. However, persons with similar CD4+ cell counts may differ with regard to clinical progression. For this reason the development of additional markers predictive of disease progression is of major clinical importance. In this review three additional progression markers are discussed: rate of decline of CD4+ cells, T-cell reactivity, and HIV biological phenotype. Besides their usefulness as independent progression markers they also provided insight into immunopathologic mechanisms responsible for the eventual development of AIDS.

Immunological and virological markers determining progression to AIDS.

Infection with the human immunodeficiency virus (HIV-1) results in a severe immunodeficiency characterized by a depletion of CD4+ T-helper cells. Furthermore it is well documented that in asymptomatic persons the number of CD4+ cells is also a good predictor of progression to AIDS. However, persons with similar CD4+ cell counts may differ with regard to clinical progression. For this reason the development of additional markers predictive of disease progression is of major clinical importance. In this review three additional progression markers are discussed: rate of decline of CD4+ cells, T-cell reactivity and HIV biological phenotype. Besides their usefulness as independent progression markers they also provide insight into the immunopathological mechanisms responsible for the final development of AIDS.

Development and evaluation of an HIV-1 transfection-neutralization assay.

We developed a transfection-neutralization assay for human immunodeficiency virus type 1 (HIV-1) infectious molecular clones. In this assay CD4 negative adherent cells, transfected in microtiter plates with fixed amounts of proviral DNA of molecular HIV-1 clones, are cocultivated with CD4 positive T cell lines or primary peripheral blood mononuclear cells (PBMC) in the presence of anti-HIV-1 sera or monoclonal antibodies (MAbs). Results obtained with this technique were reproducible and compared favorably with a conventional cell-free infection inhibition assay. The transfection-neutralization assay obviates the need for virus stock preparation and, therefore, is particularly suitable for the evaluation of HIV-1 clones with slow replication kinetics and of recombinant chimeric HIV-1 clones inclined to undergo additional mutations during stock preparation. The potential value of this assay for the analysis of the specificity of neutralizing sera and MAbs was demonstrated in experiments with V3 chimeric molecular clones.