Jan Sjölin

Intravenous Immunoglobulin G Therapy in Streptococcal Toxic Shock Syndrome: A European Randomized, Double-Blind, Placebo-Controlled Trial

The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P=.02) and 3 (P=.04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P=.03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.

Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients with streptococcal toxic shock syndrome – a comparative observational study

BACKGROUND Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis are the 2 most severe invasive manifestations caused by group A Streptococcus (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive treatment with a beneficial effect on mortality. However the clinical evidence is limited. Here we aim to further document the clinical efficacy of administered IVIG therapy in a comparative observational study of well-defined patients with STSS. METHODS The effect of IVIG was evaluated in patients with STSS prospectively identified in a nationwide Swedish surveillance study conducted between April 2002 and December 2004. Detailed data on symptoms, severity of disease, treatment, and outcome were obtained from 67 patients. Crude and adjusted analyses with logistic regression were performed. RESULTS Twenty-three patients received IVIG therapy compared with 44 who did not. No significant difference in comorbidities, severity of disease, organ failures, or sex was seen, but the IVIG group was slightly younger and had a higher degree of necrotizing fasciitis (56% vs 14%). The primary endpoint was 28-day survival. Adjusted analysis revealed that factors influencing survival in STSS were Simplified Acute Physiology Score II (odds ratio [OR], 1.1; P = .007), clindamycin (OR, 8.6; P = .007), and IVIG (OR, 5.6; P = .030). CONCLUSIONS This comparative observational study of prospectively identified STSS patients demonstrates that both IVIG and clindamycin therapy contribute to a significantly improved survival in STSS.

Granulocyte-Macrophage Colony-Stimulating Factor as Immunomodulating Factor Together with Influenza Vaccination in Stem Cell Transplant Patients

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the serological response at influenza vaccination was studied in 117 patients who had undergone stem cell transplantation (SCT). The vaccine response was evaluated as significant increases in levels of influenza hemagglutination-inhibition (HAI) antibodies and of IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). There was no difference in antibody response to either influenza A or B in 64 patients who received GM-CSF at vaccination, compared with the 53 who did not. In the subgroup of allogeneic SCT patients, HAI showed that the response rate to the influenza B vaccine was significantly higher in the treatment group (P<.05). ELISA showed that autologous SCT patients with breast cancer who received GM-CSF had a better response to influenza A (P<.05) and B (P<.01). At early vaccination, 4-12 months after stem cell transplantation, these responses were more pronounced. GM-CSF appears to improve the response to influenza vaccination in some groups of SCT patients, but only to a limited extent.

Cerebrospinal fluid shunt infections in children over a 13-year period: anaerobic cultures and comparison of clinical signs of infection with Propionibacterium acnes and with other bacteria

OBJECT Shunt infections represent a major problem with risk for sequelae and even death. The aim in this retrospective study was to analyze the incidence, origin, and clinical presentation of shunt infections, with special reference to the results of cultures for anaerobic organisms performed in addition to the usual tests, to prolonged incubation times, and to infections caused by Propionibacterium acnes. METHODS The medical records of 237 hydrocephalic children (age range 0-15 years) in whom operations were performed by a pediatric surgeon at Uppsala University Hospital during a 13-year period were reviewed. RESULTS Thirty-four verified or suspected intraventricular shunt infections and 5 distal catheter infections occurred after 474 operations. Skin bacteria, such as coagulase-negative staphylococci ([CoNS], 19 patients), Staphylococcus aureus (7 patients), and P. acnes (6 patients) predominated. The addition of anaerobic cultures and prolonged incubation times increased the verification of shunt infection by more than one third. Children with P. acnes infection were significantly older, had a lower body temperature, fewer cerebrospinal fluid (CSF) leukocytes, a higher CSF/blood glucose ratio, more distal catheter infections, and other sources of infection. Four had an abdominal pseudocyst. Children < 1 year of age and infected with CoNS were more affected than older children with systemic and local symptoms. In children with distal catheter infection and growth of propionibacteria at the time of the distal catheter and valve replacement, no follow-up antibiotic treatment was necessary. CONCLUSIONS Addition of anaerobic cultures and prolonged incubation times led to an increase in the detection of shunt infections. Infections caused by propionibacteria often result in mild symptoms that may be overlooked if adequate anaerobic cultures are not obtained.

Splanchnic and peripheral release of 3-methylhistidine in relation to its urinary excretion in human infection☆

The present investigation was undertaken in order to determine the release of 3-methylhistidine (3MH) from the splanchnic region and from the leg, and the contributions these make to the increase in urinary 3MH excretion in infection. Thirteen febrile patients with infection were investigated. After an overnight fast, hepatic vein, femoral vein, and radial artery catheterizations were performed. Splanchnic and leg blood flows were determined by dye dilution technique. Plasma 3MH was analyzed by a modified HPLC method. The release of 3MH from the leg was 0.064 +/- 0.007 mumol/min (+/- SE) and from the splanchnic region 0.012 +/- 0.013 mumol/min. These releases of 3MH constitute 27% +/- 2% and 8% +/- 6% of the individual urinary excretions, respectively. With increasing degree of catabolism, measured as individual 3MH increase above baseline excretion or as the 3MH to creatinine ratio (3MH:Cr), the relative contribution to urinary excretion from the leg was increased (individual increase, P = 0.08; 3MH:Cr, P less than 0.01). Since this contribution was not decreased in the more catabolic patients, as would have been expected if the increase in urinary 3MH originated elsewhere, it is concluded that skeletal muscle is the source, and these results thus validate the use of urinary 3MH excretion as a marker of myofibrillar protein catabolism in infected patients.

Adult Bacterial Meningitis: Earlier Treatment and Improved Outcome Following Guideline Revision Promoting Prompt Lumbar Puncture

BACKGROUND In suspected acute bacterial meningitis (ABM), cerebral computerized tomography (CT) is recommended before lumbar puncture (LP) if mental impairment. Despite guideline emphasis on early treatment, performing CT prior to LP implies a risk of delayed treatment and unfavorable outcome. Therefore, Swedish guidelines were revised in 2009, deleting impaired mental status as a contraindication for LP without prior CT scan. The aim of the present study was to evaluate the guideline revision. METHODS The Swedish quality registry for community-acquired ABM was analyzed retrospectively. Door-to-antibiotic time and outcome were compared among patients treated 2005-2009 (n=394) and 2010-2012 (n=318). The effect of different LP-CT sequences was analyzed during 2008-2012. RESULTS Adequate treatment was started 1.2 hours earlier, and significantly more patients were treated <2 hours from admission 2010-2012 than 2005-2009. Compared with CT before LP, immediate LP resulted in 1.6 hours earlier treatment, significant increase in door-to-antibiotic times of <1 and <2 hours, and a favorable outcome. In 2010-2012, mortality was lower (6.9% vs 11.7%) and the risk of sequelae at follow-up decreased (38% vs 49%) in comparison with 2005-2009. Treatment delay resulted in a significantly increased risk for fatal outcome, with a relative increase in mortality of 12.6% per hour of delay. CONCLUSIONS The deletion of impaired mental status as contraindication for prompt LP and LP without prior CT scan are associated with significantly earlier treatment and a favorable outcome. A revision of current international guidelines should be considered.

Urinary excretion of 1-methylhistidine a qualitative indicator of exogenous 3-methylhistidine and intake of meats from various sources

In order to investigate whether the urinary excretion of 1-methylhistidine (1MH) might serve as an objective indicator of meat ingestion and exogenous 3-methylhistidine (3MH) intake, healthy subjects were fed an ovolactovegetarian diet. At five-day intervals they were given meat of different origin and 24-hour urinary excretions of 1MH and 3MH were determined. After beef intake there was a marked increase of 3MH and 1MH excretion. The elimination curves were found to follow first-order kinetics and to indicate similar elimination rates. 1MH was present in ten different types of meat analyzed. A strong linear relationship was found between increase in 3MH and 1MH excretion and the amount of chicken, pork, or plaice ingested. IMH may serve as an objective indicator of meat and exogenous 3MH intake, since it is present in meat, and, regardless of source, shows similar dose-independent kinetics, and has similar half-life to 3MH.

Efficacy and Safety of Cefotaxime in Combination with Metronidazole for Empirical Treatment of Brain Abscess in Clinical Practice: A Retrospective Study of 66 Consecutive Cases

Sixty-six consecutive patients with brain abscesses referred to a department of neurosurgery during a 10-year period and treated with cefotaxime were studied retrospectively by means of a prospectively designed protocol whose main areas of emphasis were duration of antibiotic treatment, sterilization rate, clinical outcome in relation to prognostic factors, and side effects. Sixty-two of these patients were treated additionally with metronidazole, and surgery was performed in 53 patients. Mental status was altered in 33 patients, 11 of whom were comatose. Rupture of the abscess into the ventricles occurred in eight patients. Death was attributable to brain abscess formation in three patients (4.5%). Forty-six percent of the surviving patients recovered without any neurological deficits. Reversible adverse reactions, which occurred in 38 patients, were the most common reason for withdrawal of cefotaxime. In 76% of these cases, there was a significant improvement before the onset of the adverse reaction. The median duration of parenteral antibiotic treatment was 36, 41, 22, and 46 days in patients treated with excision, aspiration, evacuation of subdural empyema, and antibiotics alone, respectively. Taking prognostic factors into consideration, mortality attributable to brain abscess was lower than previously reported. This finding, along with the abscess sterilization results, indicates that cefotaxime in combination with metronidazole is a highly effective treatment but is associated with a high frequency of reversible side effects. The results indicate that a shorter duration of treatment should be investigated.

Neurosurgical Gram-Negative Bacillary Ventriculitis and Meningitis: A Retrospective Study Evaluating the Efficacy of Intraventricular Gentamicin Therapy in 31 Consecutive Cases

BACKGROUND Gram-negative bacillary (GNB) ventriculitis and meningitis are rare but serious complications after neurosurgery. Prospective studies on antibiotic treatment for these infections are lacking, and retrospective reports are sparse. At our hospital in Uppsala, Sweden, meropenem has been recommended as empirical therapy since 1996, with the addition of intraventricular gentamicin in cases that do not respond satisfactorily to treatment. In this study, we retrospectively compare the efficacy of combination treatment with intraventricular gentamicin to that of systemic antibiotics alone. In addition, we report our experience of meropenem for the treatment of GNB ventriculomeningitis. METHODS Adult consecutive patients with gram-negative bacteria isolated from cerebrospinal fluid during a 10-year period and with postneurosurgical GNB ventriculitis or meningitis were included retrospectively. Data were abstracted from the medical records. RESULTS Thirty-one patients with neurosurgical GNB ventriculitis or meningitis and follow-up for 3 months were identified. The main intravenous therapies were meropenem (n = 24), cefotaxime (n = 3), ceftazidime (n = 2), imipenem (n = 1), and trimethoprim-sulfamethoxazole (n = 1). Thirteen patients were given combination treatment with appropriate intraventricular gentamicin. These patients had a higher cure rate and a lower relapse rate than did those treated with intravenous antibiotics alone (P = .03). Relapse occurred in 0 of 13 patients treated intraventricularly and in 6 of 18 patients treated with systemic antibiotics alone. The mortality rate was 19%; 3 patients in each group died, but in no case was death considered to be attributable to meningitis. CONCLUSIONS Our results support combination treatment with intraventricular gentamicin for postneurosurgical GNB ventriculomeningitis. Meropenem seems to be an effective and safe alternative for the systemic antibiotic treatment of these neurointensive care infections.

Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome

Variants with markedly different expression of virulence factors can arise in invasive infection in humans.