Eradication of carbapenem-resistant Enterobacteriaceae gastrointestinal colonization with nonabsorbable oral antibiotic treatment: A prospective controlled trial.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics. METHODS: Consecutive hospitalized CRE carriers were studied. Patients whose rectal isolates were gentamicin sensitive but colistin resistant were treated with gentamicin. Patients whose isolates were colistin sensitive but gentamicin resistant were treated with colistin. Patients whose isolates were sensitive to both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin, colistin, or both. Patients whose isolates were resistant to both drugs, and those who did not consent, were followed for spontaneous eradication. RESULTS: One hundred fifty-two patients were included; 102 were followed for spontaneous eradication for a median duration of 140 days (controls), and 50 received 1 of the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a median duration of 33 days. Eradication rates in the 3 treatment groups were 42%, 50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous eradication rate in the control group (P < .001, P < .001, and P = .004, respectively) with no difference between the regimens. No significant adverse effects were observed. CONCLUSION: Oral antibiotic treatment with nonabsorbable drugs to which CRE is susceptible appears to be an effective and safe for eradication of CRE colonization and, thereby, may reduce patient-to-patient transmission and incidence of clinical infection with this difficult-to-treat organism.

Molecular-based diagnosis of bacteremia in the setting of fever with or without neutropenia in pediatric hematology-oncology patients.

BACKGROUND: Prompt evaluation and appropriate treatment with wide-spectrum antibiotics is considered mandatory for febrile oncology patients especially during neutropenia. Central venous catheters are widely used in pediatric oncology patients and are often the source of infections. Patients are usually admitted for follow-up and administration of antibiotics. Aims were to assess the efficacy of the polymerase chain reaction (PCR) method in identifying bacteria in blood samples as compared with standard blood cultures. METHODS: This was a prospective study, which included all patients with central venous catheters admitted to the pediatric hematology-oncology department over the 14-month period. Demographic, clinical, and laboratory variables were compared in bacteremic and nonbacteremic patients. Standard microbiological cultures were compared using the PCR technique. RESULTS: From September 2004 to November 2005, 148 blood cultures (70 patients) were evaluated. Positive blood cultures were detected on 21 (18.3%) occasions. PCR had sensitivity of 46%, specificity of 98%, positive predictive value 86%, and negative predictive value 89%. The PCR identified fastidious bacteria in 2 occasions when standard cultures were negative. CONCLUSIONS: Inspite of low sensitivity, PCR may help with early identification of bacteremia. Improving this technology is warranted.

Prolonged fever and splinter hemorrhages in an immunocompetent traveler with disseminated histoplasmosis.

We present a case of progressive disseminated histoplasmosis in an immunocompetent traveler. Histoplasmosis was acquired in South America; its manifestations included prolonged fever, splinter hemorrhages, erythema multiforme, arthritis, and mediastinal lymphadenopathy. To the best of our knowledge no splinter hemorrhages had previously been reported in a patient with histoplasmosis.

Diagnostic accuracy of PCR alone compared to galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis: a systematic review.

PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed ≥80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions.

Incidence and risk factors for endocarditis among patients with health care-associated Staphylococcus aureus bacteraemia.

BACKGROUND: Staphylococcus aureus infective endocarditis (IE) is a characteristic community-acquired infection, however most cases are presently occurring in the health care setting. This study investigated the incidence and risk factors for S. aureus IE in patients with nosocomial and health care-associated S. aureus bacteraemia (SAB). METHODS: Consecutive patients with health care-associated and hospital-acquired SAB were prospectively recruited over a 30-month period. Patients were followed up for at least 12 weeks after the initial positive blood culture result. The primary endpoint was the diagnosis of IE. RESULTS: IE occurred in 11 of 303 patients (3.6%). Patient characteristics at diagnosis and that were associated with IE included the number of positive blood cultures obtained during hospitalization (p = 0.003), the duration of bacteraemia (p < 0.001), bacteraemia persisting for > 3 days (odds ratio (OR) 14.5, 95% confidence interval (CI) 4.0-52.8; p < 0.001), performance of echocardiography (OR 1.88, 95% CI 1.69-2.1; p = 0.001), presence of a well known predisposing risk for IE (OR 57.2, 95% CI 13.6-240.5; p < 0.001), a non-fatal McCabe score (OR 2.10, 95% CI 1.4-3.1; p = 0.02), and the duration of fever related to the infection (p = 0.026). On multivariable analysis, the presence of a predisposing risk for IE, prolonged bacteraemia, and non-fatal McCabe score remained significantly associated with IE. CONCLUSIONS: In this study the incidence of IE was lower than previously reported. Three clinical characteristics were identified as risk factors for IE among patients with SAB acquired in a health care setting.

Two closely related strains associated with pertussis resurgence in Israel.

Eighty-two isolates of Bordetella pertussis analyzed by pulsed-field gel electrophoresis from the epidemic years, 2007 to 2008, revealed 4 strains with 2 closely related isolates accounting for 95% of the circulating strains. The most common Israeli strain has the same pulsed-field gel electrophoresis cluster as the dominant European BpSR11 strain (pulsed-field gel electrophoresis cluster IVß) identified in the 1999 to 2004 EU Pertstrain II project.

Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVE: Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection. METHODS: Over a 6-year period, all HIV-negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively. RESULTS: PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58). Mortality was associated with co-infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores. CONCLUSIONS: In this study, the mortality of HIV-negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR-based assay, as compared with traditional methods, for the diagnosis of PCP in HIV-negative patients.

Polymerase-chain-reaction-based diagnosis of invasive fungal pulmonary infections in immunocompromised children.

OBJECTIVE: Fungal pneumonia is a serious complication in immunocompromised children. It is difficult to diagnose because of the low sensitivity of clinical and standard laboratory tests. The aim of this study was to investigate the diagnostic impact of polymerase chain reaction (PCR) assays for fungal pathogens in bronchoalveolar lavage (BAL) fluid. STUDY DESIGN: BAL samples obtained from hospitalized immunocompromised patients with clinical pneumonia between January 2007 and June 2009 were processed for microscopy and cultures in addition to PCR-based fungal assays. The results were compared between the standard and PCR methods. RESULTS: Seventy-seven children with 100 episodes of pneumonia were included in the study. Fungal pathogens were detected by standard microbiological investigations in 10 episodes (10%) and by PCR-based assays alone in 20 episodes (20%). There was no significant difference in clinical improvement or mortality rate between patients diagnosed by the different methods. In 61 episodes, no fungal pathogen was identified by either method. Prolonged antifungal therapy was avoided in 43 episodes. CONCLUSION: PCR-based assay for the diagnosis of fungal pulmonary infections may be a useful adjunct to clinical and standard microbiological techniques. The use of PCR may decrease the time to diagnosis, increase the rate of detection of fungal pathogens, and spare patients unnecessary antifungal treatment.

Clinical spectrum and outcome of Nocardia infection: experience of 15-year period from a single tertiary medical center.

INTRODUCTION: Nocardiosis, although very rare, is considered as an important opportunistic infection; however, recent literature is limited. This study describes all cases of nocardial infection treated in the authors' hospital to provide more information about clinical manifestations, species isolated, treatment and outcome of patients with nocardiosis. METHODS: A retrospective review of the clinical features and outcome of nocardial infections was conducted during a 15-year period (1996-2010) at Rambam Health Care Campus. RESULTS: The study included 53 patients with nocardial infection, 43 of them had underlying immunodeficiency. The most common clinical form was pulmonary nocardiosis with and without dissemination (60%), followed by skin and soft tissue infection (21%), bacteremia (11%) and pertonitis (5%). Resistance to trimethoprim/sulfamethoxazile was detected in 15% of isolates; to imipenem in 5% and to ciprofloxacin in 65%. Overall mortality was 25% (13/53), mainly observed in patients with pulmonary involvement (37.5%). CONCLUSIONS: Nocardiosis is a rare infection and mainly affects immunocompromised patients. Higher index of suspicion is needed for earlier diagnosis and treatment to improve prognosis.

Polymerase chain reaction-based detection of Pneumocystis jirovecii in bronchoalveolar lavage fluid for the diagnosis of pneumocystis pneumonia.

INTRODUCTION: The diagnosis of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected immunocompromised patients is notoriously difficult. The recent advent of polymerase chain reaction (PCR)-based detection systems, based on the identification of single fungal genes, has markedly improved diagnostic accuracy in this ominous disease. In an attempt to further improve diagnostic yield, the authors used a PCR-based detection system for Pneumocystis jirovecii, based on targeting 3 distinct genes. METHODS: During the 4-year period (January 2005 to January 2009), all consecutive immunocompromised patients suspected of having PCP in the differential diagnosis underwent bronchoscopy with bronchoalveolar lavage sampling for the evaluation of the etiology of pulmonary infiltrates. Bronchoalveolar fluid was tested for the presence of a wide variety of possible etiological microorganisms. RESULTS: In a cohort of 214 immunocompromised patients (of which 198 were non-HIV immunocompromised patients) who underwent bronchoscopy with bronchoalveolar lavage for evaluation of pulmonary infiltrates, PCR correctly diagnosed PCP in 75% (42/56) compared with 14% (8/56) diagnosed by traditional stains, and increased diagnostic yield 5.4-fold. CONCLUSIONS: Given the absence of a sensitive gold standard, this study demonstrates the usefulness of a multigene PCR-based detection of Pneumocystis jirovecii DNA for supporting the clinical diagnosis of PCP, with high sensitivity and negative predictive value rates compared with direct stains, especially in non-HIV immunocompromised patients.

An outbreak of Mycobacterium mucogenicum bacteremia in pediatric hematology-oncology patients.

BACKGROUND AND AIMS: Mycobacterium mucogenicum (MM) is a rapidly growing nontuberculous mycobacterium that is commonly identified in tap water that can rarely cause bacteremia. We describe an outbreak of MM bacteremia among pediatric hematology-oncology patients. METHODS: Charts of children with MM bacteremia were retrospectively reviewed. Demographic data, underlying conditions, central venous catheter (CVC) type, duration of bacteremia, and treatment were retrieved. Epidemiologic investigation was conducted during the outbreak including environmental sampling. RESULTS: During an 8-month period (September 2005-May 2006), 8 patients aged 1.5 to 17 years had MM bacteremia. Seven patients had underlying malignancy and 1 with thalassemia major had bone marrow transplantation. The mean number of positive blood cultures was 4.2 (1-11) per patient. Two patients received antibiotic treatment in addition to removal of CVC. All patients were cured. Almost 60 environmental samples were obtained from surfaces, ice, and municipal water supply. All were negative and no source was documented. Infection control measures included emphasis on guidelines for prevention of CVC-associated infections. No cases occurred before and after this outbreak. CONCLUSIONS: MM is a rare agent of CVC-associated bacteremia. Removal of the CVC may be sufficient for management of bacteremia. In the absence of definite source identification, reinforcement of standard infection control measures can be successful in containing outbreaks.

Cutaneous nocardiosis: report of two cases and review of the literature.

BACKGROUND: Cutaneous nocardiosis is an uncommon infectious disease that presents as a primary cutaneous infection or as a disseminated disease. It is often misdiagnosed because of its rarity and nonspecific clinical picture. METHODS: We report a case of each type. The first case is an immunocompetent patient who was infected by Nocardia while gardening and developed a superficial skin infection--one of the three clinical manifestations of primary cutaneous nocardiosis. The second case is an immunocompromised patient with pulmonary nocardiosis that extended to the skin as part of a disseminated disease. RESULTS: The immunocompetent patient with primary cutaneous nocardiosis had the classical features of a superficial skin infection. He had a nodular­pustular lesion on the right arm, which appeared 7 days after gardening with bare hands. Nocardia was identified in a skin culture taken from a pustule, unfortunately not to the species level. Treatment with minocycline for 3 months resulted in full remission of the lesion. The immunocompromised patient with disseminated nocardiosis had high fever, productive cough, hemoptysis, and erythematous nodules and pustules on the extremities. N. brasiliensis was isolated from bronchial samples and skin. Treatment with a high dose of trimethoprim and sulfamethoxazole for five months resulted in full recovery from cutaneous and pulmonary complaints. No relapse of the infection was found on follow-up in either patient. CONCLUSION: These cases demonstrate the need for a high degree of suspicion, focused clinical search, and appropriate laboratory procedures in the diagnosis and management of cutaneous nocardiosis.

[Isolated congenital asplenia--a rare cause of severe pneumococcal sepsis].

Invasive disease caused by Streptococcus pneumoniae (SPn) is common among young children. Severe sepsis can be seen among those with primary or secondary immunodeficiency states. The absence of a spleen is a well-known risk factor for severe and overwhelming pneumococcal sepsis, as well as other encapsulated bacteria (e.g. Haemophilus influenzae type b (Hib), or Neisseria meningitidis). The most common cause of asplenia is surgical removal of the spleen (after trauma or as a treatment for various hematological conditions). Dysfunction of the spleen can also be seen in sickle cell disease, with high risk of invasive bacterial diseases. Primary congenital asplenia is rare. Congenital asplenia can be a part of Ivemark syndrome which is accompanied by other malformations. Isolated congenital asplenia is exceedingly rare. These patients can present with severe sepsis, meningitis or even sudden death. Overall, 31 cases have been reported, among them 17 were familial and the rest sporadic. The genetic bases for this rare life-threatening malformation are not known. The authors describe a one year old patient, presented with severe pneumococcal sepsis and multisystem organ failure. Isolated congenital asplenia was demonstrated. The child recovered and is being treated according to the recommendations for adults with asplenia.

Fatal hospital-acquired Legionella pneumonia in a neonate.

Legionnaire disease is a rare cause of community-acquired pneumonia in children and an exceedingly rare diagnosis in infants and neonates, with only few reported cases. We describe a case of fatal Legionnaire disease diagnosed by culture and polymerase chain reaction method from sputum and lung biopsy specimens, and emphasize the importance of considering this rare entity in cases of severe neonatal pneumonia.

Early-onset group B Streptococcus sepsis in high risk neonates born after prolonged rupture of membranes.

BACKGROUND: According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS status is unknown. OBJECTIVES: To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in neonates born at 35-42 weeks gestation after PROM to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis. METHODS: During a 1 year period we studied all neonates born beyond 35 weeks gestation with maternal PROM > or =18 hours, unknown maternal GBS status and without prior administration of IAP. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR. RESULTS: Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP > 1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012-2.6). CONCLUSIONS: In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

Aspergillus vertebral osteomyelitis in chronic leukocyte leukemia patient diagnosed by a novel panfungal polymerase chain reaction method.

BACKGROUND CONTEXT: Vertebral osteomyelitis and disciitis caused by Aspergillus spp is a rare event. Early diagnosis and early antifungal therapy are critical in improving the prognosis for these patients. The diagnosis of invasive fungal infections is, in many cases, not straightforward and requires invasive procedures so that histological examination and culture can be performed. Furthermore, current traditional microbiological tests (ie, cultures and stains) lack the sensitivity for diagnosis of invasive aspergillosis. PURPOSE: To present a case of vertebral osteomyelitis caused by Aspergillus spp diagnosed using a novel polymerase chain reaction (PCR) assay. STUDY DESIGN: Case report. METHODS: Aspergillus DNA was detected in DNA extracted from the necrotic bone tissue by using a "panfungal" PCR novel method. RESULTS: Treatment with voriconazole was started based on the diagnosis. CONCLUSION: Using this novel technique enabled us to diagnose accurately an unusual bone pathogen that requires a unique treatment.

Meningitis following spinal anesthesia: 6 cases in 5 years.

We describe 6 cases of meningitis after spinal anesthesia associated with a single anesthesiologist over the course of 5 years. The earliest case occurred in 2000, and the other 5 cases occurred over the course of 14 months in 2004-2005. The case identified in 2000 was culture-positive for Streptococcus salivarius. The other 5 cases were culture-negative for this organism but in 2 cases, the cerebrospinal fluid was found to be positive for bacterial DNA that was identified as belonging to S. salivarius by sequencing of the 16S rRNA gene. The association with a single anesthesiologist and a single hospital during a relatively short interval, however, lead us to believe that these occurrences are part of a series associated with possible violations of aseptic technique.