Successful control of widespread methicillin-resistant Staphylococcus aureus colonization and infection in a large teaching hospital in the Netherlands.

OBJECTIVE: The low prevalence of infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) in The Netherlands is ascribed to a national "search-and-destroy" policy. We describe the measures that were implemented to control widespread MRSA colonization and infection in a Dutch hospital. DESIGN: Descriptive intervention study. SETTING: Teaching medical center with a capacity of 679 beds, including 16 intensive care beds. INTERVENTIONS: MRSA colonization and infection were identified using conventional culture with a selective broth. Isolates were typed using pulsed-field gel electrophoresis. Measures to control the epidemic included screening of contacts (patients and hospital staff), screening of patients at readmission or discharge, strict isolation of MRSA-positive patients, decolonization of colonized staff and patients, the development of an electronic signal identifying MRSA-positive patients, and the development of a culture information-system for hospital personnel. RESULTS: Awareness of uncontrolled dissemination of MRSA began in November 2001. Because the clone involved had a low minimum inhibitory concentration for oxacillin, at first it was not recognized as MRSA. In February 2002, when major screening efforts started, it appeared that MRSA had spread all over the hospital and that many staff members were colonized. By the end of December 2005, a total of 600 patients and 135 staff members were found to be newly colonized. The yearly incidence of cases of MRSA colonization and infection decreased from 351 in 2002 to 56 in 2005. Typing of the isolates showed that 3 MRSA clones were predominant. Outbreaks of colonization involving these clones did not occur after 2003. CONCLUSION: Our observations show that strict application of "search-and-destroy" measures can effectively control a huge epidemic of MRSA colonization and infection.

Bacteriological cultures on admission of the burn patient: To do or not to do, that's the question.

INTRODUCTION: In many burn centers, routine bacteriological swabs are taken from the nose, throat, perineum, and the burn wound on admission, to check for the presence of microorganisms that require specific measures in terms of isolation or initial treatment. According to the Dutch policy of "search and destroy," for example, patients infected by multiresistant bacteria have to be strictly isolated, and patients colonized with ß-hemolytic Streptococcus pyogenes must receive antibiotic therapy to prevent failed primary closure or loss of skin grafts. In this respect, the role of bacteria cultured on admission in later infectious complications is investigated. The aim of this study is to assess systematic initial bacteriological surveillance, based on an extensive Dutch data collection. MATERIALS AND METHODS: A total of 3271 patients primarily admitted to the Rotterdam Burn Centre between January 1987 and August 2010 with complete bacteriological swabs from nose, throat, perineum, and the burn wounds were included. For this study, microbiological surveillance was aimed at identifying resistant microorganisms such as methicillin-resistant Staphylococcus aureus (MRSA), multiresistant Acinetobacter, and multiresistant Pseudomonas, as well as Lancefield A ß-hemolytic streptococci (HSA), in any surveillance culture. The cultures were labeled as "normal flora or non-suspicious" in the case of no growth or a typical low level of bacterial colonization in the nose, throat, and perineum and no overgrowth of one type of microorganism. Further, the blood cultures of 195 patients (6.0%) who became septic in a later phase were compared with cultures taken on admission to identify the role of the initially present microorganisms. Statistical analysis was performed using SPSS 20.0. RESULTS: Almost 61% of the wound cultures are "non-suspicious" on admission. MRSA was cultured in 0.4% (14/3271) on admission; 12 out of these 14 patients (85.7%) were repatriated. Overall, 9.3% (12/129) of the repatriated patients were colonized with MRSA. Multiresistant Acinetobacter or Pseudomonas was detected in 0.3% (11/3271 and 10/3271, respectively). In total, 18 of the 129 repatriated patients (14%) had one or more resistant bacteria in cultures taken within the first 24h after admission in our burn center. On admission, S. pyogenes was found in 3.6% of patients (117/3271), predominantly in children up to 10 years of age (81/1065=7.6%). CONCLUSIONS: Resistant bacteria or microorganisms that impede wound healing and cause major infections are found only in few bacteriological specimens obtained on admission of patients with burn wounds. However, the consequences in terms of isolation and therapy are of great importance, justifying the rationale of a systematic bacteriological surveillance on admission. Patients who have been hospitalized for several days in a hospital abroad and are repatriated show more colonization at admission in our burn center. The microorganisms identified are not only (multi)resistant bacteria, showing that a hospital environment can quickly become a source of contamination. These patients should receive special attention for resistant bacteria. HSA contamination is observed more frequently in younger children. Bacteria present at admission do not seem to play a predominant role in predicting later sepsis.

Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study.

PURPOSE: The aim of the study was to test the hypothesis that aerobic Gram-negative bacteria (AGNB) play a crucial role in the pathogenesis of radiation-induced mucositis; consequently, selective elimination of these bacteria from the oral flora should result in a reduction of the mucositis. METHODS AND MATERIALS: Head-and-neck cancer patients, when scheduled for treatment by external beam radiation therapy (EBRT), were randomized for prophylactic treatment with an oral paste containing either a placebo or a combination of the antibiotics polymyxin E, tobramycin, and amphotericin B (PTA group). Weekly, the objective and subjective mucositis scores and microbiologic counts of the oral flora were noted. The primary study endpoint was the mucositis grade after 3 weeks of EBRT. RESULTS: Seventy-seven patients were evaluable. No statistically significant difference for the objective and subjective mucositis scores was observed between the two study arms (p = 0.33). The percentage of patients with positive cultures of AGNB was significantly reduced in the PTA group (p = 0.01). However, complete eradication of AGNB was not achieved. CONCLUSIONS: Selective elimination of AGNB of the oral flora did not result in a reduction of radiation-induced mucositis and therefore does not support the hypothesis that these bacteria play a crucial role in the pathogenesis of mucositis.

Graft-versus-host disease following transplantation of 'one log' versus 'two log' T-lymphocyte-depleted bone marrow from HLA-identical donors.

Prevention of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, requires the depletion of mature T-lymphocytes from bone marrow grafts. The optimal degree of T-cell reduction is still an open question. We compared two procedures of T-cell separation in 18 consecutive recipients of genotypically HLA-matched bone marrow, who also received cyclosporin A for 6 months. The first method (A) was based on a discontinuous albumin gradient fractionation and resulted in an average T-lymphocyte content of 50 X 10(5)/kg body weight (n = 9 patients); the second method (B) was based on E-rosette sedimentation and reduced the contamination to 15 X 10(4) grafted T-lymphocytes/kg body weight on the average (n = 9 patients). Thus, approximately 90 and 99% of the original T-lymphocytes were removed from the marrow grafts respectively. Of the seven patients of the first group who were at risk of GVHD (excluding two cases of early death), five developed a minimal-to-moderately severe acute GVHD and in two cases chronic GVHD ensued. Lethal GVHD was not seen. Of group B, all recipients engrafted and none developed GVHD (0/9). The difference in the frequency of GVHD between the two groups was highly significant (P less than 0.0025). These data confirm our preclinical studies. They demonstrate that a one-log T-lymphocyte reduction of the marrow inoculum, when combined with cyclosporin A prophylaxis after major histocompatibility complex (MHC)-matched transplantation, is still associated with a considerable incidence of GVHD, whereas a two-log reduction of T-lymphocytes may provide full protection against acute GVHD.

Methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii: an unexpected difference in epidemiologic behavior.

BACKGROUND: The Dutch guideline on hospital policy for the prevention of nosocomial spread of methicillin-resistant Staphylococcus aureus (MRSA) states that patients transferred from hospitals abroad must be placed in strict isolation immediately on admission to a hospital in the Netherlands. Three patients colonized with both MRSA and a multiresistant Acinetobacter were transferred from hospitals in Mediterranean countries to 3 different hospitals in the Netherlands. Despite isolation precautions, Acinetobacter spread in 2 of the 3 hospitals, whereas nosocomial spread of MRSA did not occur. METHODS: For outbreak analysis, the Acinetobacter isolates, identified as Acinetobacter baumannii by the use of amplified ribosomal DNA restriction analysis, were comparatively typed by 4 methods. Comparison of isolation measures in the hospitals was performed retrospectively. RESULTS: In the 2 hospitals in which nosocomial spread of Acinetobacter occurred, most of the epidemiologically related isolates were indistinguishable from the index strains. In these 2 hospitals, isolation measures were in concordance with those recommended for the prevention of contact transmission. The precautions of the hospital in which no outbreak occurred included the prevention of airborne transmission. CONCLUSIONS: Precautions recommended for multiresistant gram-negative organisms are insufficient for the prevention of nosocomial spread of multiresistant Acinetobacter. The airborne mode of spread of acinetobacters should be taken into account, and guidelines should be revised accordingly.

Investigation of cross contamination in a Mycobacterium tuberculosis laboratory using IS6110 DNA fingerprinting.

SETTING: A laboratory for routine culturing of Mycobacterium tuberculosis. OBJECTIVE: Investigation of an episode of laboratory cross contamination using IS6110 restriction fragment length polymorphism (RFLP) typing. Improvement of laboratory protocols to prevent contaminations in the future. To stress the importance of 'good laboratory practice', and interaction with clinicians about laboratory results. DESIGN: Fingerprinting of mycobacterial isolates from 1) cultures suspected of being contaminated and 2) strains suspected of being the source of the cross-contamination. RESULTS: RFLP typing results indicated that clinical samples were contaminated by strains which had been processed in species identification procedures one day earlier in the same safety cabinet. This cross contamination also resulted in exceptional RFLP typing results--mixed banding patterns. Three patients were treated on the basis of false-positive laboratory results. Because the laboratory results were confusing for the clinicians, the treatment of one true tuberculosis patient was severely delayed. CONCLUSION: 'Good laboratory practice' is very important to prevent cross contamination. RFLP typing proved to be a useful tool to trace the source of contamination. Interaction with clinicians receiving doubtful results is of the utmost importance.

Safety and efficacy of itraconazole in prevention of fungal infections in neutropenic patients.

In a non-randomized study the efficacy of itraconazole in preventing fungal infections in neutropenic patients was investigated. Forty-seven patients with acute leukemia or advanced lymphoblastic lymphoma were enrolled. Ninety-two episodes of severe neutropenia after chemotherapy were observed. Mean duration of neutropenia was 24 days. Norfloxacin was administered as prophylaxis against gram-negative infections and itraconazole 200 mg b.i.d. as antifungal prophylaxis. Surveillance cultures of throat, urine, feces and vagina or prepuce were performed regularly. Four patients died, two patients due to heart failure, two patients due to staphylococcal pneumonia. Only in one case Candida albicans was cultured from bronchoalveolar lavage fluid. No systemic mycosis or Aspergillus fumigatus pneumonia was documented. In a similar group of patients treated in the preceding 18 months nystatin was used as antifungal prophylaxis. In this group of patients six cases of Aspergillus fumigatus pneumonia, two cases of Candida albicans fungemia and one case of Candida glabrata pneumonia occurred of which six patients died. Itraconazole seems to be effective in preventing fungal infections in neutropenic patients and is well tolerated.

[Necrotizing fasciitis caused by Group A beta-hemolytic streptococci]. / Necrotiserende fasciitis door beta-hemolytische streptokokken uit groep A.

A case is presented of a 35-year-old man with necrotizing fasciitis caused by group A beta-haemolytic Streptococci, accompanied by severe systemic toxicity, and necessitating amputation of the leg. After prolonged intensive care treatment the patient recovered.

[Outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in the Rijnmond region: the largest outbreak in the Netherlands]. / Uitbraak van meticillineresistente Staphylococcus aureus (MRSA) in de regio Rijnmond: grootste MRSA-epidemie in Nederland.

UNLABELLED: EPIDEMIC: The annual number of new MRSA isolates in the Netherlands tripled in 2002 compared with previous years. This increase was in part due to a MRSA outbreak in the Rijnmond region. The outbreak occurred in two merged hospitals and is the largest ever to occur in the Netherlands. From November 2001 till June 2003 MRSA was isolated from 381 patients and 113 hospital employees. The worst affected departments were Surgery and Internal Medicine. One MRSA strain (pulsed-field gel electroforesis (PFGE) type 16) remained initially unrecognised and was therefore able to spread unnoticed. Soon two additional epidemic MRSA strains (types 37 and 38) were discovered. DISCUSSION: Multiple factors played a role in the extent and duration of the outbreak. Because of the delayed detection and rapid spread of MRSA type 16, the outbreak grew too large once recognised to be resolved within the available infrastructure. Investments were needed at various fields, including the infection-control service and the microbiology laboratory. Employees had to be informed and motivated, and a separate MRSA ward and OPD were provided. New MRSA outbreaks occurred, despite extensive MRSA (contact) screening among patients and employees. The numbers of isolates began falling as from the beginning of 2003.

[Clinical thinking and decision making in practice. A young woman with fever, arthralgia and exanthema]. / Klinisch denken en beslissen in de praktijk. Een jonge vrouw met koorts, artralgie en exantheem.

A 19-year-old woman was admitted because of high fever, rash, arthralgia and sore throat. On physical examination a diffuse skin rash was observed, leaving a facial mask unaffected. C-reactive protein and erythrocyte sedimentation rate were raised (114 mg/l and 26 mm in the first hour, respectively); white blood cell count was normal (6.2 x 10(9)/l) with an increased count of immature forms. An infective, metabolic or haematological cause was excluded. Serum ferritin turned out to be extremely elevated (4318 micrograms/l), so adult-onset Still's disease was diagnosed. The patient fulfilled the criteria of Cush et al. for adult-onset Still's disease. She was first treated with non-steroidal anti-inflammatory drugs (NSAIDs) and, at a later stage in the disease, with corticosteroids. All symptoms disappeared and blood test results normalised.

Isolation efficiency and its clinical importance in patients with burns.

Nine severely burned patients were submitted to reverse isolation in a mass airflow system. Their burns became colonized by Enterobacteriaceae biotypes which were not found in the patients own flora on admission. They were, therefore, probably derived from the food which was obtained from the central kitchen. These strains did not cause bacteriaemia. Suggestions to improve the isolation efficiency are made.

The use of a human donor flora for recontamination following antibiotic decontamination.

A method to prevent endogenous infections in patients and laboratory animals with an impaired immune capacity is the total decontamination of the gastrointestinal tract. This is performed by oral administration of nonabsorbable antibiotics. One of the disadvantages of total decontamination is the fact that especially after termination of this treatment the decontaminated individual is easily colonized with organisms from the environment. This is the result of the elimination of the anaerobic part of the microflora, which is responsible for the so-called colonization resistance (CR). This CR is the resistance against exogenous microorganisms to colonize the gastrointestinal tract. In the absence of an anaerobic flora, the colonizing microorganisms can reach abnormally high faecal concentrations, thus increasing the risk for infection. In mice, the implantation of an anaerobic, mouse-derived flora after termination of total decontamination resulted in the restoration of a good CR, as could be shown by orally challenging the animals with a strain of Escherichia coli. Therefore, an anaerobic microflora, free of potentially pathogenic microorganisms, which was isolated from a healthy human volunteer was administered to monkeys and patients after a decontamination period in an attempt to restore CR. In the monkeys, this human donor flora (HDF) did not reduce the faecal concentration of microorganisms that had colonized the gastrointestinal tract before the donor microflora had been established, in contrast to the findings in some of the patients. Qualitative analysis of the microflora of patients which were contaminated with the human donor flora showed that the CR is not of the same quality as is found in healthy individuals. This can be the result of the impaired immune capacity of the patients at the time of HDF implantation. However, the results obtained show that implantation of the HDF in monkeys and patients after a decontamination period allows reconventionalization without an undue risk of microbial infection.

Recontamination after gastrointestinal decontamination with non-absorbable antibiotics.

In an attempt to restore the colonization resistance we administered anaerobic microflora to prevent an abnormal colonization of the intestine after antibiotic treatment had been discontinued. After the antibiotics had been discontinued and before the donor flora had been administered and had colonized the intestine, microorganisms present were "unopposed" and expanded to a high density. A mouse model was used to investigate which antibiotics negatively influenced the donor flora and reduced the colonization resistance when administered intraperitoneally. Erythromycin, clindamycin and carbenicillin suppressed the donor flora permanently, as could be seen by the reduced colonization resistance. Benzylpenicillin, ampicillin, doxycycline and the combination gentamicin-cephalothin affected the colonization resistance as long as these agents were present. Gentamicin alone and cephalothin and oxytetracycline had no effect on the colonization resistance.