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Background The quick sequential organ failure assessment (qSOFA) score predicts mortality in patients with suspected infection. We sought to understand how well qSOFA and the Systemic Inflammatory Response Syndrome (SIRS) criteria predict gram negative bacteraemia. Methods We prospectively evaluated 99 patients with gram negative bloodstream infection from a single tertiary centre. We assessed the utility of SIRS and qSOFA for their rate of positivity and association with early delivery of antibiotics ( Results The SIRS criteria had the highest positivity rate amongst patients with gram negative bacteraemia (85%) compared to the qSOFA criteria (25%) on the day of first positive culture. Positive SIRS criteria was the only score associated with delivery of antibiotics within 3 h (Relative risk 3.5, 95% Confidence interval 1.3 to 12.5, p= Conclusion In patients with gram negative bloodstream infection SIRS criteria was the most common positive risk score and had a higher association with early delivery of antibiotics when compared to qSOFA.

ESBL-producing Enterobacteriaceae as uropathogens have given rise to a sizeable amount of global morbidity. Community and hospital surveillance studies continue to report increasing proportions of these organisms as causes of urinary tract infection (UTI). Due to limited treatment options and the presence of cross-resistance amongst oral antibiotics of different classes, patients often require IV therapy, thereby increasing healthcare costs and reducing the effectiveness of delivering healthcare. Oral cephalosporin antibiotics are well known for their ability to achieve high urinary concentrations, in addition to achieving clinical success for treatment of uncomplicated UTI with a drug-susceptible pathogen. Novel cephalosporin/β-lactamase inhibitor combinations have been developed and demonstrate good in vitro activity against ESBL-producing isolates. A pooled analysis of in vitro activity of existing oral cephalosporin/clavulanate combinations in ESBL-producing Enterobacteriaceae has shown MIC50s of 0.5–1, 0.125–1 and 0.25 mg/L for cefpodoxime, ceftibuten and cefixime, respectively. A novel cyclic boronic acid β-lactamase inhibitor, QPX7728, was able to produce MIC50 values of 0.5 and ≤0.06 mg/L when paired with cefpodoxime and ceftibuten, respectively. Other novel combinations, cefpodoxime/ETX0282 and ceftibuten/VNRX7145, have also demonstrated excellent activity against ESBL producers. Clinical trials are now awaited.

Background Carbapenems are recommended treatment for serious infections caused by AmpC-producing gram-negative bacteria but can select for carbapenem resistance. Piperacillin-tazobactam may be a suitable alternative. Methods We enrolled adult patients with bloodstream infection due to chromosomal AmpC producers in a multicenter randomized controlled trial. Patients were assigned 1:1 to receive piperacillin-tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours. The primary efficacy outcome was a composite of death, clinical failure, microbiological failure, and microbiological relapse at 30 days. Results Seventy-two patients underwent randomization and were included in the primary analysis population. Eleven of 38 patients (29%) randomized to piperacillin-tazobactam met the primary outcome compared with 7 of 34 patients (21%) in the meropenem group (risk difference, 8% [95% confidence interval {CI}, –12% to 28%]). Effects were consistent in an analysis of the per-protocol population. Within the subcomponents of the primary outcome, 5 of 38 (13%) experienced microbiological failure in the piperacillin-tazobactam group compared to 0 of 34 patients (0%) in the meropenem group (risk difference, 13% [95% CI, 2% to 24%]). In contrast, 0% vs 9% of microbiological relapses were seen in the piperacillin-tazobactam and meropenem arms, respectively. Susceptibility to piperacillin-tazobactam and meropenem using broth microdilution was found in 96.5% and 100% of isolates, respectively. The most common AmpC β-lactamase genes identified were blaCMY-2, blaDHA-17, blaCMH-3, and blaACT-17. No ESBL, OXA, or other carbapenemase genes were identified. Conclusions Among patients with bloodstream infection due to AmpC producers, piperacillin-tazobactam may lead to more microbiological failures, although fewer microbiological relapses were seen. Clinical Trials Registration NCT02437045.

Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial.

Purpose of Review The aim of this article is to review current and emerging microbiological techniques that support the rapid diagnosis of bacterial infections in critically ill patients, including their performance, strengths and pitfalls, as well as available data evaluating their clinical impact. Recent Findings Bacterial infections and sepsis are responsible for significant morbidity and mortality in patients admitted to the intensive care unit and their management is further complicated by the increase in the global burden of antimicrobial resistance. In this setting, new diagnostic methods able to overcome the limits of traditional microbiology in terms of turn-around time and accuracy are highly warranted. We discuss the following broad themes: optimisation of existing culture-based methodologies, rapid antigen detection, nucleic acid detection (including multiplex PCR assays and microarrays), sepsis biomarkers, novel methods of pathogen detection (e.g. T2 magnetic resonance) and susceptibility testing (e.g. morphokinetic cellular analysis) and the application of direct metagenomics on clinical samples. The assessment of the host response through new “omics” technologies might also aid in early diagnosis of infections, as well as define non-infectious inflammatory states. Summary Despite being a promising field, there is still scarce evidence about the real-life impact of these assays on patient management. A common finding of available studies is that the performance of rapid diagnostic strategies highly depends on whether they are integrated within active antimicrobial stewardship programs. Assessing the impact of these emerging diagnostic methods through patient-centred clinical outcomes is a complex challenge for which large and well-designed studies are awaited.

Background COVID‐19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS‐CoV‐2 as a cause of subacute thyroiditis (SAT). Methods A systematic review was conducted in accordance with the PRISMA guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms “COVID‐19”, “SARS‐CoV‐2” and “coronavirus” along with search terms “thyroiditis”, “thyrotoxicosis”, “thyroid” were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. Results 15 publications reporting on 17 individual cases of COVID‐19 induced SAT were identified. Age ranged from 18 to 69 years old. The majority of the cases were female (14 of 17, 82%). The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome (SIRS) related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated CRP was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Anti‐thyroid antibodies were frequently negative. SAT specific treatment included corticosteroids for 12/17 (70.5%) patients. Most return to normal thyroid status. Conclusion COVID‐19 associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross‐over of common clinical features between COVID‐19 and thyrotoxicosis. This article is protected by copyright. All rights reserved.

Background Antimicrobial susceptibility testing (AST) is the standard of care for treating bacterial infections. In randomized clinical trials of new antimicrobials, AST might not be performed or reported in real time. Objectives To determine local, real-time laboratory AST performance, its usage in the trial flow, quality control (QC) of the local testing, central AST performance and the effect of using AST categorization on the trials' primary outcomes. Data sources We systematically searched PubMed, Embase, PsychINFO and Web of Science. Eligibility criteria We included registered randomized controlled trials published in journals between January 2015 and December 2019. Participants and interventions We included trials comparing different antibiotics for the treatment of infections caused predominantly by Gram-negative bacteria. Methods Primary outcomes for different trial populations were extracted and differences between trial arms were compared for patients with infections caused by susceptible versus non-susceptible bacteria. Results are described narratively. Results Of 32 randomized trials, 25 trials reported that local AST was performed, 1312 reported the local laboratory AST methods, no trial reported QC, but post-hoc referral for AST at a reference laboratory was common. Patients' outcomes were superior when patients with infections due to susceptible and non-susceptible pathogens were compared post hoc (median difference 14%, interquartile range 8%–24%) in trials allowing this comparison (seven antimicrobials), except for colistin, where 14-day mortality was 9% higher when patients were treated with colistin for colistin-susceptible versus colistin-resistant carbapenem-resistant Acinetobacter baumannii. When excluding patients with pathogens that were non-susceptible to either antimicrobial in the trials, the difference in the primary outcome between the trial arms was reduced in five out of six trials. Conclusions Trials should perform AST to guide patient inclusion or exclusion from the study and consider the impact of the central laboratory susceptibility results on the study outcomes when using post-hoc reference testing.

Cefepime, a wide-spectrum β-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with β-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.

Carbapenem-sparing regimens are needed for the treatment of infections caused by extended-spectrum-β-lactamase (ESBL)- and AmpC-producing members of the Enterobacterales. We sought to compare the clinical efficacy of ceftazidime/avibactam and carbapenems against ESBL- and AmpC-producing Enterobacterales species. A systematic review and meta-analysis of randomized controlled trials comparing ceftazidime/avibactam with carbapenems for the treatment of ESBL- and AmpC-producing Enterobacterales was conducted. Five randomized controlled trials (RCTs) with ESBL- and AmpC-specific outcome data were compiled. Of the 246 patients infected with an ESBL-producing microorganism in the ceftazidime/avibactam arm, 224 (91%) had a clinical response at test of cure (TOC), versus 240 of 271 (89%) patients in the carbapenem arm (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97 to 1.08; P = 0.45; I(2) = 0%). Clinical response rates for AmpC producers in the ceftazidime/avibactam and carbapenem arms were 32/40 (80%) and 37/42 (88%), respectively (RR, 0.91; 95% CI, 0.76 to 1.10; P = 0.35; I(2) = 0%). Microbiological response and mortality rates were not reported specifically for ESBL/AmpC producers. Ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intra-abdominal infections caused by ESBL-producing Enterobacterales species, and the data are too limited to provide any conclusive recommendations for the AmpC producers. Care should be taken before extrapolating this to severe infections, given that the representation of this population in the reviewed studies was negligible. Ceftazidime/avibactam is a costly drug active against carbapenem-resistant microorganisms and should be used judiciously to preserve its activity against them.

Background Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli. Methods This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected. Discussion Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024. Trial registration The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390. Registered on 23 January 2020.

Achromobacter is a genus of nonfermenting Gram-negative bacteria under order Burkholderiales. Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g., most cephalosporins, aztreonam, and aminoglycosides), and are increasingly acquiring resistance to carbapenems. Carbapenem resistance is mainly caused by multidrug efflux pumps and metallo-β-lactamases, which are not expected to be overcome by new β-lactamase inhibitors. Among the other new antibiotics, cefiderocol, and eravacycline were used as salvage therapy for a limited number of patients with Achromobacter infections. In this article, we aim to give an overview of the antimicrobial resistance in Achromobacter species, highlighting the possible place of new antibiotics in their treatment.

Despite the accepted dogma that antibiotic use is the largest contributor to antimicrobial resistance (AMR) and human microbiome disruption, our knowledge of specific antibiotic-microbiome effects remains basic. Detection of associations between new or old antimicrobials and specific AMR burden is patchy and heterogeneous. Various microbiome analysis tools are available to determine antibiotic effects on microbial communities in vivo. Microbiome analysis of treatment groups in antibiotic clinical trials, powered to measure clinically meaningful endpoints would greatly assist the antibiotic development pipeline and clinician antibiotic decision making.

PURPOSE OF REVIEW: Multidrug-resistant (MDR) Gram-negative bacteria infections are listed among the top public health threats of the current era. As a result, there has been an increase in efforts to develop new therapeutic agents against MDR Gram-negatives. The purpose of this review is to summarize the clinical and preclinical findings associated with recently approved drugs and the drugs in clinical development against ESBL and carbapenemase-producing Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii infections. RECENT FINDINGS: There are a number of ESBL active agents in late stage clinical development that can help spare carbapenems. Likewise, recently approved β-lactam/β-lactamase inhibitor combinations allow a change in the treatment of KPC and OXA-48 producers and carbapenem-resistant P. aeruginosa from colistin to new, safer agents. Treatment of Meta-beta-lactamase (MBL) producers remains an unmet need - apart from cefiderocol, most agents with MBL activity are still in clinical development. Among the few agents with carbapenem-resistant A. baumannii activity, durlobactam/sulbactam in phase III clinical trials provides hope. SUMMARY: Armamentarium against MDR Gram-negatives has expanded with the dominance of agents active against ESBL and KPC producers. There is a need to prioritize MBL producers and carbapenem-resistant A. baumannii, as well as the need for clinical trials to test the new agents against serious infections.

Diarrhoea that occurs during or after recent travel is predominantly infectious in nature; however, in atypical or prolonged cases a broader range of aetiologies for diarrhoea must be considered, and a careful history and examination may reveal clues to more sinister causes of diarrhoea. We report two cases in which a recent travel history and a positive stool culture or polymerase chain reaction testing for bacterial pathogens delayed the diagnosis of ulcerative colitis. As a result of severe inflammatory bowel disease, colectomy was the final result in both cases. Early consideration of causes other than infection for traveller's diarrhoea may prevent unnecessary morbidity in young patients.

Background: Extended spectrum beta‐lactamase (ESBL) and AmpC‐producing Enterobacterales are prevalent worldwide. Poor clinical outcomes, including death, are more common in patients both colonised and infected with these organisms1. Australia is thought to have a comparatively low prevalence of such organisms, however no clear continuous surveillance system exists2. Specific ESBL type has shown significant geographic variation, having different therapeutic and infection control implications for different regions3. Little is known about the prevalence, molecular type and spread of ESBL and AmpC‐producing Enterobacterales among hospitalised patients in the Sunshine Coast region. Aims: To (i) Determine the prevalence and molecular epidemiology of ESBL and AmpC‐producing Enterobacterales, (ii) Develop an in‐house multiplex polymerase chain reaction (PCR) assay to detect common ESBL genes, (iii) Compare our PCR assay to the double disc diffusion method for detection of ESBLs, and to (iv) Establish, with whole genome sequencing (WGS), whether transmission was occurring in our intensive care unit (ICU). Methods: Clinical specimens from adult and paediatric patients culturing Enterobacterales resistant to a third‐generation cephalosporin were collected prospectively from July 2017 to August 2018 at the Sunshine Coast University Hospital laboratory. Antibiotic susceptibility testing was determined using VITEK‐2®. A validated in‐house pentaplex PCR assay was developed and used to detect common beta‐lactamase genes (CTX‐1, CTX‐9, SHV, TEM, CMY). All isolates collected from patients admitted to the ICU were identified and underwent WGS analysis using the Illumina® platform. Results: 295 clinical specimens were identified. Escherichia coli (78.8%), Klebsiella pneumoniae (16.8%) with 1‐2% consisting of Enterobacter spp., Serratia marcescens and Citrobacter freundii. Specimens included urine (53.8%), rectal swab (39.4%), pus (3.0%) and blood (2.4%). Carbapenem resistance was observed in 3.3%. ICU patient specimens made up 18.2%. The majority (87.8%) of isolates had at least one gene identified on PCR testing of which 48.5% produced CTX‐1, 31.2% produced CTX‐9, 15.9% produced SHV, 12.5% produced CMY and 40.6% produced TEM. Approximately forty percent of isolates produced more than one ESBL with the most common being CTX‐1 and TEM coproduction. A small amount (

Primary cutaneous Mycobacterium avium complex (MAC) infection is a rare diagnosis in both immunocompetent and immunocompromised hosts. Disseminated MAC almost always occurs in the setting of advanced HIV infection and typically results from initial pulmonary or gastrointestinal disease. We describe a case of a 70-year-old female with systemic sclerosis and severe tumoral calcinosis that developed disseminated MAC infection secondary to deep cutaneous disease. Treatment was complicated by multiple significant drug interactions, patient comorbidities, as well as an inability to safely and completely surgically resect her infected soft tissue for source control.

Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary treatment modality used to treat haematological malignancies. Lymphocytes are engineered to produce CARs directed towards tumour cell antigens. Clinical trials have demonstrated impressive malignancy-related outcomes. Unfortunately, numerous off-target effects can cause toxicity-related adverse events in this population, the main being cytokine release syndrome and immune effector cell neurotoxicity syndrome. This causes significant patient morbidity and poor outcomes. Patients who receive CAR T-cell therapy are also profoundly immunosuppressed and often cytopenic, which is caused by a multitude of patient- and treatment-related factors. Thus, infection-related complications are also common in this group. Indeed, up to one third of patients will suffer a serious bacterial infection in the first 30 days after therapy. Viral respiratory tract infection appears to be the most common during the late phase and can be severe; one patient has died of influenza A infection. Fungal infection and cytomegalovirus (CMV) reactivation appear to be uncommon. Although institutional guidelines on infection-prevention strategies are available, there is a dearth of evidence to support their approach. Future research needs to target important unanswered questions that remain in this patient population in order to improve their short- and long-term outcomes.

Coxiella burnetii infection is not known to involve directly the kidneys. Kidney injury associated with Q fever usually manifests in the setting of chronic infection or endocarditis with development of immune complex deposition. Acute kidney injury (AKI) in the context of acute Q fever infection may be more pathologically heterogeneous. We describe two cases of severe AKI secondary to acute Q fever infection, each with marked differences in pathological characteristics, and clinical course.

Carbapenemase-producing Enterobacteriaceae (CPE) contribute significantly to the global public health threat of antimicrobial resistance. OXA-48 and its variants are unique carbapenemases with low-level hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. bla(OXA-48) is typically located on a plasmid but may also be integrated chromosomally, and this gene has progressively disseminated throughout Europe and the Middle East. Despite the inability of OXA-48-like carbapenemases to hydrolyze expanded-spectrum cephalosporins, pooled isolates demonstrate high variable resistance to ceftazidime and cefepime, likely representing high rates of extended-spectrum beta-lactamase (ESBL) coproduction. In vitro data from pooled studies suggest that avibactam is the most potent beta-lactamase inhibitor when combined with ceftazidime, cefepime, aztreonam, meropenem, or imipenem. Resistance to novel avibactam combinations such as imipenem-avibactam or aztreonam-avibactam has not yet been reported in OXA-48 producers, although only a few clinical isolates have been tested. Although combination therapy is thought to improve the chances of clinical cure and survival in CPE infection, successful outcomes were seen in ∼70% of patients with infections caused by OXA-48-producing Enterobacteriaceae treated with ceftazidime-avibactam monotherapy. A carbapenem in combination with either amikacin or colistin has achieved treatment success in a few case reports. Uncertainty remains regarding the best treatment options and strategies for managing these infections. Newly available antibiotics such as ceftazidime-avibactam show promise; however, recent reports of resistance are concerning. Newer choices of antimicrobial agents will likely be required to combat this problem.

Highlights • Rhodococcus equi infection primarily causes pneumonia but can disseminate to cause disease in virtually any human tissue. • Increasing recognition that this pathogen can cause disease in both immunocompetent and immunocompromised hosts. • Two cases of invasive R. equi infection at both ends of the spectrum in terms of susceptibility and severity of disease. • High index of suspicion in a broad range of settings and communication with microbiologist is essential for early diagnosis., Rhodococcus equi is a gram positive bacterium most commonly presenting clinically as pneumonia, however can disseminate to cause disease in virtually any human tissue. Although it is predominantly an opportunistic pathogen, a number of case series have described infection occurring among individuals with a normal immune system. We describe two cases of Rhodococcus equi infection which highlight the diversity of disease presentations of this rare organism.

Antimicrobial resistance is a major threat to the delivery of effective care and already causes 700000 excess deaths per year worldwide. International consensus on action to combat antimicrobial resistance was reached in 2015. Australia is implementing a national strategy. The clinical consequences of antimicrobial resistance are seen most acutely in multi-drug resistant Gram-negative bacterial infections, where they cause increased mortality and morbidity and threaten the delivery of once routine medical care. The solution to antimicrobial resistance is complex and multifaceted. Antimicrobial stewardship, that is optimising the use of the antibiotics we currently have, is the most rapidly deployable mitigation. Several novel antibiotics with activity against a range of drug-resistant bacteria are now available clinically, leading to hope that innovative solutions will reduce the impact of resistance. It is critical that these new drugs are protected from inappropriate use.

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE) are becoming increasingly more prevalent and provide significant morbidity and mortality. Providing curative therapy and overcoming bacterial resistance are difficult tasks with limited antibiotic options. Alternative antibiotics and approaches to therapy are required, with often a compromise in patient outcome.To demonstrate the effective use of therapeutic drug monitoring (TDM) in difficult-to-treat infections due to multiresistant gram-negative bacteria.A case of an elderly woman with an invasive cervical spine infection due to CRE is presented. Her protracted therapeutic course was complicated by multiple treatment failures and severe cervical spine instability. Therapeutic success, as determined by wound healing, cervical spine stability, and continued suppression of inflammatory markers, was obtained by continuous daily ertapenem infusions with TDM guiding the optimal drug dosing.In this unusual setting, TDM was utilized successfully to achieve favorable serum antibiotic concentrations and lead to control of the infection. TDM may be a useful tool in difficult-to-treat infections caused by multiresistant bacteria.

Queensland tick typhus (QTT; Rickettsia australis) is an important cause of community-acquired acute febrile illness in eastern Australia. Cases of QTT were identified retrospectively from 2000 to 2015 at five sites in Northern Brisbane through a pathology database. Those included had a fourfold rise in spotted fever group (SFG)-specific serology, a single SFG-specific serology ≥ 256 or SFG-specific serology ≥ 128 with a clinically consistent illness. Cases were excluded on the basis of clinical unlikelihood of QTT infection. Thirty-six cases were included. Fever was found in 34/36 (94%) patients. Rash occurred in 83% of patients with maculopapular being the dominant morphology (70%). Thrombocytopenia, lymphopenia, and raised transaminases were common and occurred in 58%, 69%, and 89% of patients, respectively. Thirty-one of 36 (86%) patients received antibiotic therapy (usually doxycycline) and the time to correct antibiotic (from admission) ranged from 3 to 120 h (mean 45.5 h). Four of 36 (11%) required intensive care unit (ICU) admission for severe sepsis and end-organ support. There were no deaths. QTT has a wide range of clinical and laboratory features. Early and appropriate antimicrobial therapy is important and may prevent severe disease. Further prospective studies are required to identify factors associated with severe infection and sepsis.