Michael S. Gelfand

Enterobacter sakazakii infections in neonates associated with intrinsic contamination of a powdered infant formula.

We report an outbreak of Enterobacter sakazakii infection and colonization in neonates related to an infant formula contaminated during the manufacturing process. The outbreak occurred in a 20-bed neonatal intensive care unit during a six-week period in 1988, and involved a total of four infants. Three infants had sepsis and three had bloody diarrhea; all patients responded to intravenous antibiotics and recovered without complications. The E sakazakii isolated from the formula had the same plasmid and multilocus enzyme profile as those isolated from patients. This outbreak demonstrates the significance of commercially contaminated formulas and emphasizes the need to limit contamination and multiplication of bacteria in enteral formulas.

Blastomycosis in immunocompromised patients.

Among the endemic mycoses, blastomycosis has been least often associated with disorders of immune function, but the data presented herein suggest that blastomycosis may occur more commonly in immunocompromised patients than was previously recognized. We have observed a marked increased in the number of immunocompromised patients with blastomycosis over the last 15 years, increasing from about 3% of patients seen between 1956 and 1977 to almost 24% patients seen between 1978 and 1991. The disease appears to be much more aggressive in immunocompromised than in normal hosts. Almost 30% of the patients in our series died secondary to blastomycosis, with most deaths occurring within 5 weeks following the diagnosis. Furthermore, almost one third of those patients who died of other causes had evidence of persistent blastomycosis at death. Multiple organ and central nervous system involvement were relatively common in this series. For these reasons, early and aggressive therapy with amphotericin B is indicated for most immunocompromised patients with blastomycosis. Oral therapy with an azole compound should probably be reserved for patients who have responded to a primary course of amphotericin B but who require additional or long-term suppressive therapy. Until more data are available, the newer azoles should be used with caution as primary therapy in immunocompromised patients with blastomycosis, and considered only in patients with limited disease and a stable underlying condition. Caring for the immunocompromised patient poses many diagnostic and therapeutic challenges to the clinician, and among those patients who have been exposed to areas endemic for blastomycosis, B. dermatitidis must be regarded as a potentially important opportunistic pathogen.

Vancomycin‐resistant Enterococcus bacteremia: An evaluation of treatment with linezolid or daptomycin

BACKGROUND Due to high rates of resistance and a limited number of efficacious antimicrobials for vancomycin-resistant Enterococcus (VRE), appropriate antibiotic selection is vital to treatment success. The purpose of this study was to assess clinical and microbiologic outcomes associated with the use of linezolid or daptomycin in the treatment of VRE bacteremia. METHODS A retrospective analysis of adult patients with VRE bacteremia between January 2004 and July 2009 was conducted at a tertiary care hospital in the United States. Clinical and microbiologic outcomes for both therapies were evaluated using multiple criteria. RESULTS Of the 361 patients with VRE bacteremia identified, 201 were included in the study (linezolid group, n = 138; daptomycin group, n = 63). More patients in the daptomycin group had hematologic malignancies (33% vs 14%) or received liver transplants (13% vs 4%). There was no difference in clinical or microbiologic cure between the linezolid and daptomycin groups (74% vs 75% and 94% vs 94%, respectively). Recurrence was documented in 3% of linezolid patients vs 12% of daptomycin patients (P = 0.0321). Reinfection was noted in 1% of patients in the linezolid group vs 6% of patients in the daptomycin group (P not significant). The average length of stay (LOS) was 37 days for the linezolid group vs 40 days for the daptomycin group (P not significant). Overall mortality was 20%, occurring in 25/138 linezolid patients vs 15/63 daptomycin patients (P not significant). CONCLUSIONS No differences in clinical or microbiologic cure rates, LOS, or mortality were identified between the groups. Various factors may have contributed to the significantly higher recurrence of VRE bacteremia in daptomycin patients. This study suggests that linezolid and daptomycin appear equally efficacious in the treatment of VRE bacteremia.

A five-year multicenter study of the susceptibility of the Bacteroides fragilis group isolates to cephalosporins, cephamins, penicillins, clindamycin, and metronidazole in the United States

Over 2800 clinical strains of the Bacteroides fragilis group were collected during a 5-year period from ten geographically separate sites and tested for their susceptibility to various antimicrobial agents using a broth microdilution method. Among the cephalosporins, ceftizoxime was the most active (13% resistance) and importantly exhibited relatively equal activity against both B. fragilis species and non-B. fragilis species. Cefotaxime exhibited similar activity with an overall resistance rate of 18%. Both ceftriaxone and cefoperazone were appreciably less active cephalosporins especially against non-B. fragilis species. With regard to cephamycins, cefoxitin (MIC90, 32 micrograms/ml) was more active than cefotetan (MIC90, > or = 256 micrograms/ml) and cefmetazole (MIC90, 64 micrograms/ml). Non-B. fragilis species were highly resistant to cefotetan and cefmetazole. Imipenem was highly active against all strains with the exception of four strains of B. fragilis. Ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam were all highly active with resistance rates < 2%. No resistance was detected to metronidazole, whereas 14% of isolates were resistant to clindamycin. When compared with other studies, these findings underscore the wide variability in susceptibility patterns reported nationwide and the need to continue monitoring these patterns to aid in choosing the most active compounds for therapy.

The rapid emergence of fluoroquinolone-methicillin-resistant Staphylococcus aureus infections in a community hospital: An in vitro look at alternative antimicrobial agents

The introduction of ciprofloxacin on an unrestricted basis into a 900-bed community hospital resulted in the emergence of high-level fluoroquinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) during the subsequent 18 months. Susceptibility testing revealed several old and new compounds to which all the S. aureus strains were susceptible. When an MRSA strain became resistant to ciprofloxacin it also exhibited high-level resistance to ofloxacin, fleroxacin, norfloxacin, and enoxacin. Two new experimental fluoroquinolones, WIN 57273 and CI-960, exhibited good activity against all test strains. Among the glycopeptide compounds, mupirocin and teicoplanin were approximately fourfold more active than vancomycin and ramoplanin. Rifampin and trimethoprim-sulfamethoxazole (TMP/SMZ) showed good activity against most strains as did imipenem. For clindamycin, gentamicin, and tetracycline susceptibilities exhibited a bimodal distribution with at least 10% of strains having resistant MIC values. Surprisingly, the addition of sulbactam potentiated the activity of ampicillin against the ciprofloxacin-resistant MRSA strains, however, sulbactam had little effect on cefoperazone activity against these same strains. Time-kill kinetic studies of selected antimicrobials against ciprofloxacin-resistant strains indicated good killing by vancomycin, ampicillin-sulbactam, and TMP/SMZ. Teicoplanin was less bactericidal than vancomycin while these same strains rapidly developed resistance to rifampin even at concentrations 8 x MIC. These data indicate certain alternative compounds within our study warrant further investigation, especially in vivo, against multiply-resistant staphylococci.

Telavancin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis

Sir, With a rapid increase in invasive infections caused by methicillinresistant Staphylococcus aureus (MRSA), there is a demand for antimicrobials with enhanced activity against MRSA. The concentration-dependent, bactericidal lipoglycopeptide telavancin was approved in 2009 for treatment of complicated skin and skin-structure infections due to susceptible organisms. The emergence of glycopeptide resistance and clinical failures of vancomycin therapy in invasive MRSA infections, including osteomyelitis, has led to the unlabelled use of alternatives to vancomycin for treatment of these infections. We report four patients with MRSA osteomyelitis who failed standard vancomycin therapy and were successfully retreated with telavancin and surgical intervention. A patient was admitted with inability to ambulate for 1 day. This was preceded by a 4 day history of progressive leg weakness and a 2 month history of lower back pain. There also was a history of multiple carbuncles of the face, neck and buttocks, but no antimicrobial therapy had been administered for these. No fever was present. White blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated. Magnetic resonance imaging (MRI) revealed T4–7 vertebral osteomyelitis as well as T5–6 discitis with an anterior epidural phlegmon and stenosis with spinal cord compression. T5–6 laminectomy with drainage of the epidural abscess and decompression of the spinal cord was performed. Treatment with cefepime 2 g intravenously (iv) every 8 h and vancomycin 18 mg/kg iv every 12 h was begun. Blood cultures were negative, but MRSA was identified from culture of the abscess 72 h later. Vancomycin MIC was 2 mg/L, linezolid MIC was 2 mg/L and daptomycin MIC was 1 mg/L. Therapy was changed to daptomycin 6 mg/kg iv daily. After the back pain and WBC were noted to have improved, the patient was discharged to a physical rehabilitation centre to complete a planned 8 week course of daptomycin. Two weeks later, because of progressive leg weakness, fever and re-elevation of WBC, ESR and CRP values, the patient was readmitted. MRI showed recurrent epidural abscess at T5–6. T4–6 laminectomy was performed with drainage of the recurrent abscess and cord decompression. Culture of the abscess again grew MRSA (vancomycin MIC 2 mg/L, daptomycin MIC 1 mg/L and telavancin MIC 0.38 mg/L). Treatment was changed to telavancin 10 mg/kg iv daily. While receiving 10 weeks of telavancin therapy, there was resolution of fever and leucocytosis and normalization of ESR and CRP values. Gradual recovery of leg strength and ability to ambulate was noted. There was no evidence of recurrent infection 4 months after completion of telavancin. A patient with the sudden onset of leg weakness and urinary incontinence was transferred from another hospital after a lengthy hospitalization with MRSA bacteraemia (vancomycin MIC 1 mg/L, linezolid MIC 2 mg/L and daptomycin MIC ≤0.5 mg/L) from cellulitis complicated by sepsis, respiratory failure with pneumonia, renal dysfunction and hepatic encephalopathy. Despite sequential treatment with adequate doses of vancomycin (14 days), linezolid (7 days) and daptomycin (14 days), the MRSA bacteraemia persisted with unchanged MIC values. Fever was absent. WBC, ESR and CRP values were elevated. Transthoracic echocardiography and transoesophageal echocardiography (TOE) did not reveal valvular vegetations. MRI showed an epidural abscess extending from T6 to L2, L1 vertebral osteomyelitis and a left psoas abscess. Telavancin 10 mg/kg iv daily was begun. T6–7 decompressive laminectomy was performed and the abscess was evacuated. Cultures of the blood and abscess grew MRSA with unchanged MIC values of vancomycin, linezolid and daptomycin. Telavancin MIC was 0.25 mg/L. Telavancin was administered for 8 weeks with improvement in leg weakness and normalization of WBC, ESR and CRP values. There was no evidence of recurrence 7 months after completion of telavancin. A patient presented with a 1 week history of right hip pain after a fall. Fever and leucocytosis were present. There was a remote history of a gunshot wound to the right hip. CT revealed a 2 cm mass in the left upper lung and a large right hip effusion. MRI was consistent with right hip septic arthritis and osteomyelitis of the right acetabulum, femoral head, femoral neck and lesser trochanter. Blood cultures grew MRSA (vancomycin MIC 1 mg/L, linezolid MIC 1 mg/L and daptomycin MIC ≤0.5 mg/L). Ceftriaxone 2 g iv daily and vancomycin 13 mg/kg iv every 12 h were begun and continued for 5 days. Research letters

Vancomycin therapy and the progression of methicillin-resistant Staphylococcus aureus vertebral osteomyelitis.

Vancomycin therapy is the standard treatment for methicillin-resistant Staphylococcus aureus (MRSA), the most common cause of vertebral osteomyelitis, an increasingly frequent complication of nosocomial bacteremia. We report five recent cases suggesting that, while giving the appearance of success by conventional clinical and laboratory criteria (eg, resolution of fever and leukocytosis), vancomycin monotherapy may in fact be insufficient to prevent or reverse the progression of hematogenous MSRA vertebral osteomyelitis. A review of the literature and possible therapeutic alternatives are also discussed.

Pathological Fracture in Acute Osteomyelitis of Long Bones Secondary to Community-Acquired Methicillin-Resistant Staphylococcus aureus: Two Cases and Review of the Literature

Pathologic fracture is a rare complication of acute bacterial osteomyelitis in adults. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has been increasingly reported in skin and soft tissue and systemic infections in children and adults, including many cases of osteomyelitis. We recently treated two adult patients with acute osteomyelitis of long bones secondary to CA-MRSA complicated by a pathologic fracture. In both patients, the primary source of dissemination to the bone was a skin and soft tissue infection. We speculate that virulence factors specific for CA-MRSA currently circulating in the United States may predispose to a complicated course of acute osteomyelitis.

Community-Acquired Methicillin-Resistant Staphylococcus aureus and Lemierre Syndrome

Lemierre syndrome is usually caused by Fusobacterium necrophorum, but we recently encountered a case due to methicillin-resistant Staphylococcus aureus and complicated by sigmoid sinus thrombosis and cranial neuropathies. Therapy may be made more difficult by unusual organisms and also create the need for therapy that penetrates into the central nervous system.

A case of disseminated histoplasmosis following autologous stem cell transplantation for Hodgkin's lymphoma: an initial misdiagnosis with a false-positive serum galactomannan assay.

Abstract: Systemic histoplasmosis is uncommonly reported in patients who have undergone bone marrow or solid organ transplantation. Diagnosis of systemic histoplasmosis in recipients of transplants may be hampered by lack of consideration of this infection in the differential diagnosis and may be confounded by conflicting information from other testing performed to evaluate for opportunistic infections in this population. We report successful treatment of a case of disseminated histoplasmosis in a patient with Hodgkins lymphoma who had undergone autologous stem cell transplantation. The diagnosis was delayed by the finding of a positive serum galactomannan assay.