Patrick G. P. Charles

Treatment Outcomes for Serious Infections Caused by Methicillin-Resistant Staphylococcus aureus with Reduced Vancomycin Susceptibility

Although infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS) have been reported from a number of countries, including Australia, the optimal therapy is unknown. We reviewed the clinical features, therapy, and outcome of 25 patients with serious infections due to SA-RVS in Australia and New Zealand. Eight patients had endocarditis, 9 had bacteremia associated with deep-seated infection, 6 had osteomyelitis or septic arthritis, and 2 had empyema. All patients had received vancomycin before the isolation of SA-RVS, and glycopeptide treatment had failed for 19 patients (76%). Twenty-one patients subsequently received active treatment, which was effective for 16 patients (76%). Eighteen patients received linezolid, which was effective in 14 (78%), including 4 patients with endocarditis. Twelve patients received a combination of rifampicin and fusidic acid. Surgical intervention was required for 15 patients (60%). Antibiotic therapy, especially linezolid with or without rifampicin and fusidic acid, in conjunction with surgical debulking is effective therapy for the majority of patients with serious infections (including endocarditis) caused by SA-RVS.

Clinical Features Associated with Bacteremia Due to Heterogeneous Vancomycin-Intermediate Staphylococcus aureus

We assessed all episodes of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia at our hospital during a 12-month period (n=53) and compared those due to heterogeneous vancomycin-intermediate S. aureus (hVISA; n = 5, 9.4%) with those due to vancomycin-susceptible MRSA (n=48). Patients with hVISA bacteremia were more likely to have high bacterial load infections (P=.001), vancomycin treatment failure (persistent fever and bacteremia for >7 days after the start of therapy; P<.001), and initially low serum vancomycin levels (P=.006). These clinical markers of hVISA bacteremia may help focus diagnostic efforts and treatment.

SMART-COP: A Tool for Predicting the Need for Intensive Respiratory or Vasopressor Support in Community-Acquired Pneumonia

BACKGROUND Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

The Etiology of Community-Acquired Pneumonia in Australia: Why Penicillin plus Doxycycline or a Macrolide Is the Most Appropriate Therapy

BACKGROUND Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Good Clinical Outcomes but High Rates of Adverse Reactions during Linezolid Therapy for Serious Infections: a Proposed Protocol for Monitoring Therapy in Complex Patients

ABSTRACT We assessed the toxicity and clinical outcomes associated with linezolid therapy (mean duration, 29 ± 28 days; range, 8 to 185 days) in 44 patients with serious gram-positive infections. Although a clinical cure was achieved in 73% of the cases, 28/44 (64%) had adverse reactions (thrombocytopenia, n = 13; anemia, n = 7; gastrointestinal, n = 12; peripheral neuropathy, n = 1; serotonin syndrome, n = 1), such that a systematic monitoring protocol was developed.

Comparing the pneumonia severity index with CURB-65 in patients admitted with community acquired pneumonia

Pneumonia severity assessment systems such as the pneumonia severity index (PSI) and CURB-65 were designed to direct appropriate site of care based on 30-d mortality. Increasingly they are being used to guide empirical antibiotic therapy and also possibly to detect patients who will require admission to the intensive care unit (ICU). We retrospectively reviewed the records of all patients admitted to our institution with confirmed community acquired pneumonia (CAP) for the 12 months from January 2002. 408 episodes were studied with an overall 30-d mortality of 15.4% and ICU admission of 10.5%. PSI classes IV/V were significantly better than CURB-65 score≥3 for predicting patients who died within 30 d (94% vs 62%; p<0.001), and those that needed ICU (86% vs 61%; p=0.01). In addition, for the patients identified as ‘low risk’ by PSI (classes I/II), there was only 1 death and 1 admission to an ICU compared to 8 deaths and 7 ICU admissions with CURB-65 scores of 0–1. Although easier to use, CURB-65 is neither sensitive nor specific for predicting mortality in CAP patients. Neither rule was sufficiently accurate for predicting need for an ICU, even when patients with ‘not for resuscitation’ orders were excluded.

Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit.

We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option.

Comparison of the bacterial isolates and antibiotic resistance patterns of elderly nursing home and general community patients

Background:  Nursing home‐acquired infections may differ from general community‐acquired infections in bacteriology and antibiotic resistance. However, there are currently limited data on this topic in the Australian setting.

Pooled Human Immunoglobulin Therapy in Critically Ill Patients With Pandemic 2009 Influenza A(H1N1) Pneumonitis and Immunoglobulin G2 Subclass (IgG2) Deficiency

To the Editor—We have previously reported an association between IgG2 deficiency and severe H1N1 infection [1]. We now describe 5 such patients who were failing antiviral therapy and were treated with intravenous immunoglobulin (IVIG) as potential salvage therapy. The patient clinical characteristics, laboratory features, treatment, tolerability, and overall outcomes are described in Table 1. All patients had known risk factors for severe H1N1 infection (pregnancy, n 5 2; asthma, n 5 1; obesity and asthma, n 5 1; chronic lymphocytic leukemia plus high-dose corticosteroids, n 5 1). All patients required mechanical ventilation (mean, 19 days; range, 5–38 days) and 3 required extracorporeal membrane oxygenation (ECMO; mean, 13 days; range, 9–17 days). IVIG was administered after mean illness duration

Safety and Efficacy Review of Doxycycline

Doxycycline is a member of the tetracycline class of antibiotics and has been used clinically for more than 40 years. It is a well-tolerated drug that is bacteriostatic and acts via the inhibition of bacterial ribosomes. It is generally given at a dose of 100-mg daily or twice daily. It is well absorbed and has generally good tissue penetration. The serum half-life is 18-22 hours and dosage does not need to be adjusted in the presence of renal or hepatic impairment. Major side effects are gastro-intestinal and dermatological and it is generally contra-indicated in pregnancy or childhood because of concerns about discolouration of developing teeth and potential effects on growing bones. Drug interactions are not common although can occur with the concomitant use of methotrexate and the oral contraceptive pill, and its absorption can be reduced by the co-administration with some antacids and iron preparations. It has activity against many organisms, including Gram-positives, Gram-negatives and atypical bact...