Bénédicte Delaere

Another case of “European hantavirus pulmonary syndrome” with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Clinical profiles of patients colonized or infected with extended-spectrum beta-lactamase producing Enterobacteriaceae isolates: a 20 month retrospective study at a Belgian University Hospital.

BackgroundDescription of the clinical pictures of patients colonized or infected by ESBL-producing Enterobacteriaceae isolates and admitted to hospital are rather scarce in Europe. However, a better delineation of the clinical patterns associated with the carriage of ESBL-producing isolates may allow healthcare providers to identify more rapidly at risk patients. This matter is of particular concern because of the growing proportion of ESBL-producing Enterobacteriaceae species isolates worldwide.MethodsWe undertook a descriptive analysis of 114 consecutive patients in whom ESBL-producing Enterobacteriaceae isolates were collected from clinical specimens over a 20-month period. Clinical data were obtained through retrospective analysis of medical record charts. Microbiological cultures were carried out by standard laboratory methods.ResultsThe proportion of ESBL-producing Enterobacteriaceae strains after exclusion of duplicate isolates was 4.5% and the incidence rate was 4.3 cases/1000 patients admitted. Healthcare-associated acquisition was important (n = 104) while community-acquisition was less frequently found (n = 10). Among the former group, two-thirds of the patients were aged over 65 years and 24% of these were living in nursing homes. Sixty-eight (65%) of the patients with healthcare-associated ESBL, were considered clinically infected. In this group, the number and severity of co-morbidities was high, particularly including diabetes mellitus and chronic renal insufficiency. Other known risk factors for ESBL colonization or infection such as prior antibiotic exposure, urinary catheter or previous hospitalisation were also often found. The four main diagnostic categories were: urinary tract infections, lower respiratory tract infections, septicaemia and intra-abdominal infections. For hospitalized patients, the median hospital length of stay was 23 days and the average mortality rate during hospitalization was 13% (Confidence Interval 95%: 7-19). Escherichia coli, by far, accounted as the most common ESBL-producing Enterobacteriaceae species (77/114; [68%]) while CTX-M-1 group was by far the most prevalent ESBL enzyme (n = 56).ConclusionIn this retrospective study, the clinical profiles of patients carrying healthcare-associated ESBL-producing Enterobacteriacae is characterized by a high prevalence rate of several major co-morbidities and potential known risk factors. Both, the length of hospital stay and overall hospital mortality rates were particularly high. A prospective case-control matched study should be designed and performed in order to control for possible inclusion bias.

Implementation of a protocol for administration of vancomycin by continuous infusion: pharmacokinetic, pharmacodynamic and toxicological aspects.

Optimising antibiotic administration is critical when dealing with pathogens with reduced susceptibility. Vancomycin activity is dependent on the area under the concentration-time curve over 24 h at steady-state divided by the minimum inhibitory concentration (AUC/MIC), making continuous infusion (CI) or conventional twice daily administration pharmacodynamically equipotent. Because CI facilitates drug administration and serum level monitoring, we have implemented a protocol for CI of vancomycin by: (i) examining whether maintaining stable serum concentrations (set at 25-30 mg/L based on local susceptibility data of Gram-positive target organisms) can be achieved in patients suffering from difficult-to-treat infections; (ii) assessing toxicity (n = 94) and overall efficacy (n = 59); and (iii) examining the correlation between AUC/MIC and the clinical outcome in patients for whom vancomycin was the only active agent against a single causative pathogen (n = 20). Stable serum levels at the expected target were obtained at the population level (loading dose 20mg/kg; infusion of 2.57 g/24 h adjusted for creatinine clearance) for up to 44 days, but large intrapatient variations required frequent dose re-adjustments (increase in 57% and decrease in 16% of the total population). Recursive partitioning analysis of AUC/MIC ratios versus success or failure suggested threshold values of 667 (total serum level) and 451 (free serum level), corresponding to organisms with a MIC>1 mg/L. Nephrotoxicity potentially related to vancomycin was observed in 10% of patients, but treatment had to be discontinued in only two of them.

Ecthyma gangrenosum in a non-neutropaenic, elderly patient: case report and review of the literature.

Abstract Ecthyma gangrenosum is a cutaneous infection most commonly associated with Pseudomonas aeruginosa bacteraemia, but it may also be encountered after breakdown of mechanical defence barriers and local infection. The characteristic lesions of ecthyma gangrenosum are haemorrhagic blisters with surrounding erythema that rapidly evolve to necrotic ulcers. A high mortality rate is reported, especially when diagnosis is delayed and in the absence of appropriate therapy. Ecthyma gangrenosum usually occurs in critically ill and immunocompromized patients. Haematological malignancies and neutropaenia are the major risk factors, but other comorbidities (e.g. diabetes mellitus and malnutrition) have also been involved. Here, we report a case of ecthyma gangrenosum in a non-neutropaenic elderly patient with multiple comorbidities and review the literature on ecthyma gangrenosum.

Reversion of resistance in relapsing infection caused by a glycopeptide-intermediate methicillin-resistant Staphylococcus aureus isolate.

Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to glycopeptides, also referred to as glycopeptide-intermediate S. aureus (GISA), have been reported worldwide and been associated with glycopeptide treatment failure [1]. However, the clinical significance of strains with heterogeneousintermediate resistance to glycopeptides (hGISA) is much more controversial [1]. We report here a very unusual clinical observation of in vivo reversion of glycopeptide resistance in a GISA isolate, which occurred in the setting of complicated and relapsing MRSA infection. An 80-year-old man with a history of diabetes mellitus and a bilateral hip prosthesis underwent cardiac surgery with mitral plasty and valvular replacement in March 2005. Early postoperative complications required two additional surgical operations and led to the implantation of a definitive pacemaker on day 5 following the initial surgery. One month after cardiac valve replacement, the patient developed sepsis with a concomitant sternal wound infection. Several blood cultures yielded a MRSA isolate (MRSA1). Transesophageal cardiac echography (TEE) showed no signs suggestive of endocarditis and no additional images on the pacemaker. Complete surgical debridement and drainage of the sternal wound was performed, and microbiological culture of all per-operative samples grew the same MRSA isolate (MRSA1). Rifampin and gentamicin were added to the 6-week course of vancomycin that was administered via continuous infusion; gentamicin was discontinued after 2 weeks. The concentration of vancomycin in serum was monitored and no trough serum level below 20 mg/l was detected. One month after the end of antimicrobial therapy, a new episode of bacteremia occurred with an MRSA isolate possessing the same susceptibility profile as MRSA1 but with added resistance to rifampin (MRSA2). A control TEE was unrevealing, but a computed tomography (CT) scan showed dorsal vertebral spondylodiscitis. Vancomycin therapy was reintroduced for 8 weeks, and during the first 4 weeks it was administered in association with gentamicin. Again, the early clinical outcome seemed favorable. However, clearance of bacteremia was delayed and was only achieved after 10 days of treatment. A second relapse of MRSA bacteremia was recorded 2 weeks after the end of vancomycin treatment. MICs of vancomycin and teicoplanin were determined and the presence of a GISA isolate was documented (MRSA3). No primary source of infection could be identified despite extensive radiographic and scintigraphic investigations (TEE, thoracoabdominal and vertebral CT scans). The patient was treated with vancomycin and gentamicin for Eur J Clin Microbiol Infect Dis (2007) 26:419–422 DOI 10.1007/s10096-007-0297-1

Clinical case of cfr-positive MRSA CC398 in Belgium.

Sir, Linezolid, the first member of the oxazolidinone class of antibiotics, is one of the major antimicrobial agents used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. This drug inhibits bacterial protein synthesis by binding to domain Vof the 23S ribosomal RNA (rRNA) of the 50S subunit. Several mechanisms conferring linezolid resistance have been described in staphylococci, including point mutations in genes encoding 23S rRNA and mutations in ribosomal proteins L3, L4 and L22 [1, 2]. Even more problematic is the identification of cfr, a horizontally transferable resistance gene that encodes a ribosomal methyltransferase conferring cross-resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin A (PhLOPSA phenotype) [1, 2]. Recently, a new gene (optrA) coding for an ABC transporter which confers resistance to oxazolidinones and phenicol resistance has been described. Yet, this new gene has only been found in enterococci and S. sciuri [3, 4]. Despite its clinical use for more than 15 years, linezolid resistance remains scarce and is mostly due to the presence of chromosomal mutations. A recent study regarding the continuous long-term and stable in vitro activity of linezolid against different bacteria (including S. aureus, coagulasenegative staphylococci, Enterococcus spp. and Streptococcus spp.) [5] showed that none of the 7541 collected organisms harboured the cfr gene. However, wewere recently confronted with the management of one case of a human infection caused by a cfr-positive MRSA belonging to the livestock-associated (LA-) clone ST398, which is, to the best of our knowledge, the first clinical case reported in Belgium. A 74-year-old man was admitted to hospital for a postoperative skin and soft tissue infection complicating a left carotid endarterectomy performed 2 weeks earlier. Cultures of the purulent discharge grew mixed abundant organisms consisting of Escherichia coli and an MRSA. Amoxicillin– clavulanic acid was the only antimicrobial agent administered in the last several years. After surgical drainage, antimicrobial therapy was started with intravenous vancomycin to achieve serum concentrations of 20 to 30 mg/L plus piperacillin–tazobactam (4/0.5 g q.i.d.). The therapy was switched after 6 days to an oral combination of cefuroxime axetil 500 mg t.i.d. and trimethoprim–sulphamethoxazole 160/800 mg b.i.d. for a total period of 14 days. This medico-surgical management lead to total resolution and cure of infection. As the MRSA isolate collected from the patient’s sample was tested to be resistant to linezolid by the VITEK 2 system, it was sent for confirmation to the National Reference Centre (NRC) for staphylococci. At the NRC, the identification was further confirmed genotypically by polymerase chain reaction (PCR) for the detection of 16S, mecA and nuc genes, as previously described [6]. Isolates were further tested by multilocus sequence typing (MLST) (http://saureus.mlst. net/). Antimicrobial susceptibility was determined by the disc diffusion method for the following antibiotics: cefoxitin, gentamicin, kanamycin, tobramycin, fusidic acid, * H. Paridaens henry.paridaens@gmail.com

When polymerase chain reaction does not help: cytomegalovirus pneumonitis associated with very low or undetectable viral load in both blood and bronchoalveolar lavage samples after lung transplantation.

Cytomegalovirus (CMV) pneumonitis occurs frequently among solid organ transplant recipients and is classically associated with significant viral replication in both blood and bronchoalveolar lavage (BAL) samples. We present a case of a 64‐year‐old lung transplant recipient who presented with CMV pneumonitis that was diagnosed based on the association of viral inclusion in the BAL sample, rapid response to ganciclovir, and absence of other infectious etiology. Surprisingly, we observed very low or undetectable viral load both in blood and BAL samples. Diagnosis of CMV pneumonitis should rely on the association of clinical, pathological, radiological, and microbiological signs, while quantitative nucleic acid amplification testing should be interpreted with caution.

VERTEBRAL OSTEOMYELITIS WITH SPINAL EPIDURAL ABSCESS IN TWO PATIENTS WITH BACTEROIDES FRAGILIS BACTERAEMIA

Abstract We report 2 cases of vertebral osteomyelitis and contiguous epidural abscess due to Bacteroides fragilis with no concomitant or past intra-abdominal infection. Decompressive surgery with laminectomy was required for both patients due to the occurrence of neurologic deficits. Clinical recovery was achieved after 8 weeks of antibiotic therapy. It included 3 weeks of intravenous therapy with clindamycin followed by an oral regimen of clindamycin for 1 patient and oral metronidazole for the other. In both cases, magnetic resonance imaging (MRI) has proved to be essential for diagnostic. The primary source of infection remained unknown despite careful investigations.

Effect of a 5-year multidisciplinary collaborative program on antibiotic consumption in an acute geriatric ward

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Central skull base osteomyelitis: a rare but life-threatening disease

Abstract We present the case of a 70-year-old non-diabetic patient who presented to the emergency department with unrelenting otalgia. A severe otitis externa (OE) and mastoiditis were treated with broad spectrum antibiotics and surgical drainage. No bacteria was isolated from surgical samples. Because the otalgia persisted, a magnetic resonance (MR) was performed and showed an infiltrating process at the skull base. Biopsies failed to prove malignancy or granulomatosis. The patients neurological state deteriorated. The suspicion of a skull base osteomyelitis (SBO) was raised and proven by CT-guided biopsies that grew Pseudomonas aeruginosa. Meropenem and ciprofloxacin, given for 8 weeks, lead to a fast clinical improvement and a full recovery. SBO is uncommon, often complicating severe OE. Pseudomonas aeruginosa is the main pathogen. Prompt diagnosis and adequate antibiotherapy are required to lower mortality and morbidity. The diagnosis may be delayed because of unawareness and large differential diagnosis including solid neoplasic tumours, malignant hemopathies and granulomatosis.