Diabetic foot infection and osteomyelitis. Are deep-tissue cultures necessary?

INTRODUCTION: Diabetic foot infections (DFIs) are common and difficult to treat. The objective of this study was to compare swab and tissue cultures as indicators of appropriate treatment of DFIs. METHODS: This is a prospective study conducted during a 4-year period. All patients with DFIs and/or diabetic foot osteomyelitis (DFO) admitted to the University Hospital of Heraklion, Greece, were included. Clinical data were collected, while cultures taken with swabs and/or tissue biopsies were used as indicators of the microbiological cause and the appropriate treatment. RESULTS: In total, 83 individuals (62.7% males) with mean age of 72 years, were enrolled. Coexisting osteomyelitis was present in 18.1%. From tissue and pus cultures, 131 and 176 pathogens, respectively, were isolated. Gram-positive aerobes were the most common microorganisms, followed by Gram-negatives. Infection was polymicrobial in 40 (70.2%) out of 57 patients with tissue culture and in 54 (75.0%) out of 72 with pus culture. Microbiological results from tissue cultures were compatible with those from pus at a rate of 80%, while in cases of osteomyelitis concordance reached 100%. Multidrug-resistant organisms (MDROs) were isolated from 32 (24.4%) tissue and 44 (25%) pus cultures (p=0.910). Initial empirical antimicrobial treatment was considered inappropriate in 44.6% of cases. CONCLUSIONS: A high concordance between easily taken swab cultures and those taken by biopsy was noted, especially in DFO. This was helpful for early change to appropriate treatment in cases where MDROs were isolated and empirical treatment was inappropriate. Further research is needed to confirm this observation in clinical practice.

Author Correction: Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.

The original version of this Article contained an error in the spelling of the author Emilien Etienne, which was incorrectly given as Emilien Ettiene. These errors have now been corrected in both the PDF and HTML versions of the Article.

Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.

Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi.

Predisposing factors, clinical characteristics and outcome of Pneumonocystis jirovecii pneumonia in HIV-negative patients.

Pneumocystis jirovecii (former carinii) pneumonia, is a life-threatening opportunistic infection occurring in immunocompromised hosts. The aim of this study was to investigate the predisposing factors, clinical features and outcome of Pneumocystis pneumonia (PCP) in HIV-negative patients. The medical records of 62 adult patients with PCP, hospitalized at the University Hospital of Heraklion, Crete, Greece during a 10-year period (2004-2013) were retrospectively reviewed. All patients were immunosuppressed prior to the development of PCP. Thirty one patients (50%) suffered malignant hematological disease, 16 (26%) solid tumor and 15 (24%) had chronic inflammatory disease. Only 17 (27%) had received long-term systemic corticosteroids. All had symptoms of pneumonia upon admission, while 12 (19%) were suffering respiratory failure. Twenty one (34%) had received trimethoprim/sulfamethoxazole (TMP-SMX) prophylaxis before the PCP onset. Eight patients (13%) were admitted to the ICU. Mortality attributable to PCP reached 29%. Mortality attributable to PCP was higher in patients with solid tumors. TMP-SMX prophylaxis failed in a significant portion of the present cohort. Hence, PCP should be included in the differential diagnosis in immunocompromised patients with symptoms from the respiratory tract even if TMP-SMX has been given as prophylaxis.

Predisposing factors, clinical characteristics and outcome of Pneumonocystis jirovecii pneumonia in HIV-negative patients.

Pneumocystisjirovecii (former carinii) pneumonia, is a life-threatening opportunistic infection occurring in immunocompromised hosts. The aim of this study was to investigate the predisposing factors, clinical features and outcome of Pneumocystis pneumonia (PCP) in HIV-negative patients. The medical records of 62 adult patients with PCP, hospitalized at the University Hospital of Heraklion, Crete, Greece during a 10-year period (2004-2013) were retrospectively reviewed. All patients were immunosuppressed prior to the development of PCP. Thirty one patients (50%) suffered malignant hematological disease, 16 (26%) solid tumor and 15 (24%) had chronic inflammatory disease. Only 17 (27%) had received long-term systemic corticosteroids. All had symptoms of pneumonia upon admission, while 12 (19%) were suffering respiratory failure. Twenty one (34%) had received trimethoprim/sulfamethoxazole (TMP-SMX) prophylaxis before the PCP onset. Eight patients (13%) were admitted to the ICU. Mortality attributable to PCP reached 29%. Mortality attributable to PCP was higher in patients with solid tumors. TMP-SMX prophylaxis failed in a significant portion of the present cohort. Hence, PCP should be included in the differential diagnosis in immunocompromised patients with symptoms from the respiratory tract even if TMP-SMX has been given as prophylaxis.

A prospective study of characteristics and outcomes of bacteremia in patients with solid organ or hematologic malignancies.

OBJECTIVE: To study the epidemiology and outcomes of bacteremia in patients with hematologic or solid organ malignancies cared for at the University Hospital of Heraklion, Greece. METHODS: This prospective study was conducted during a 4-year period (2007-2011). Patients with bacterial and fungal blood stream infections were followed until discharge. Mortality was the primary outcome, while duration of hospitalization, relapses, time to relapse, and defervescence were the secondary outcomes. RESULTS: Ninety-nine patients with neoplasia (104 episodes) were included. Bacteremia developed mainly in patients with hematologic malignancies (56%). Secondary bacteremias due to respiratory and urinary tract infections were most commonly identified. Gram-negative bacteria were the predominantly isolated pathogens (65%); Pseudomonas spp. was the most common cause (19%), followed closely by E. coli (18%) and Klebsiella pneumoniae (17%). In-hospital mortality was 26.2%. No differences in mortality were seen among patients in different subgroups according to isolated bacteria (according to Gram's stain, species, or number of isolated bacteria in positive cultures), hematologic or solid organ malignancy, neutropenia, and primary or secondary bacteremia. However, patients with bacteremia due to extensively drug resistant bacteria had higher mortality than patients with bacteremia due to multidrug resistant or susceptible pathogens. Patients required a prolonged period of hospitalization (21.8 ± 14.9 days), which was complicated with relapses or reinfections in another body site in 27 % of them. CONCLUSION: Gram-negative bacteria were the predominantly isolated pathogens from patients with cancer in our population. The overall mortality remains high.