Range Of Serious Infections Research Articles

Meropenem-induced Haematological Abnormalities in the Elderly: A Series of Three Cases

Meropenem is a broad-spectrum antibacterial agent given empirically for diseases caused by single or multiple susceptible bacteria in both adults and children with a wide range of serious infections. Several studies have reported an association between meropenem and haematological abnormalities such as leukopenia, thrombocytopenia, neutropenia, and haemolytic anaemia. In this case series, the authors present three cases - one with meropenem-induced leukopenia and the other two with meropeneminduced thrombocytopenia. In the first case, leukopenia was observed on the third day of administration. The leukocyte count dropped to 3,500 cells/mcL but recovered upon discharge. In the other two cases, the platelet count dropped below 1.3 lac/cu.mm on the fourth day of administration but started to recover once the antibiotic was discontinued. This underscores the importance of being vigilant and conducting regular laboratory blood counts when administering antibiotics like meropenem to prevent lifethreatening complications.

Diclofenac and Meloxicam Exhibited Anti-Virulence Activities Targeting Staphyloxanthin Production in Methicillin-Resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus) is a worldwide leading versatile pathogen that causes a wide range of serious infections. The emergence of antimicrobial resistance against S. aureus resulted in an urgent need to develop new antimicrobials in the new era. The methicillin-resistant S. aureus (MRSA) prevalence in hospital and community settings necessitates the discovery of novel anti-pathogenic agents. Staphyloxanthin (STX) is a key virulence factor for the survival of MRSA against host innate immunity. The current work aimed to demonstrate the anti-virulence properties of meloxicam (MXM) as compared to diclofenac (DC), which was previously reported to mitigate the virulence of multidrug-resistant Staphylococcus aureus and test their activities in STX production. A total of 80 S. aureus clinical isolates were included, wherein a qualitative and quantitative assessment of STX inhibition by diclofenac and meloxicam was performed. The quantitative gene expression of STX biosynthetic genes (crtM, crtN and sigB) and hla (coded for α-hemolysin) as a virulence gene with and without DC and MXM was conducted, followed by molecular docking analysis for further confirmation. DC and MXM potently inhibited the synthesis of STX at 47 and 59 µg/mL to reach 79.3-98% and 80.6-96.7% inhibition, respectively. Treated cells also revealed a significant downregulation of virulence genes responsible for STX synthesis, such as crtM, crtN and global transcriptional regulator sigB along with the hla gene. Furthermore, computational studies unveiled strong interactions between the CrtM binding site and DC/MXM. In conclusion, this study highlights the potential role and repurposing of DC and MXM as adjuvants to conventional antimicrobials and as an anti-virulent to combat MRSA infections.

In Vitro and In Vivo Activity of Gepotidacin against Drug-Resistant Mycobacterial Infections.

Mycobacterial pathogens, including nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis, are pathogens of significant worldwide interest owing to their inherent drug resistance to a wide variety of FDA-approved drugs as well as causing a broad range of serious infections. Identifying new antibiotics active against mycobacterial pathogens is an urgent unmet need, especially those antibiotics that can bypass existing resistance mechanisms. In this study, we demonstrate that gepotidacin, a first-in-class triazaacenapthylene topoisomerase inhibitor, demonstrates potent activity against M. tuberculosis and M. fortuitum, as well as against other clinically relevant NTM species, including fluoroquinolone-resistant M. abscessus. Furthermore, gepotidacin exhibits concentration-dependent bactericidal activity against various mycobacterial pathogens, synergizes with several drugs utilized for their treatment, and reduces bacterial load in macrophages in intracellular killing assays comparably to amikacin. Additionally, M. fortuitum ATCC 6841 was unable to generate resistance to gepotidacin in vitro. When tested in a murine neutropenic M. fortuitum infection model, gepotidacin caused a significant reduction in bacterial load in various organs at a 10-fold lower concentration than amikacin. Taken together, these findings show that gepotidacin possesses a potentially new mechanism of action that enables it to escape existing resistance mechanisms. Thus, it can be projected as a potent novel lead for the treatment of mycobacterial infections, particularly for NTM, where present therapeutic interventions are extremely limited.

Label-free rapid isolation of saccharomyces cerevisiae with optically induced dielectrophoresis-based automatic micromanipulation.

Saccharomyces cerevisiae is well-known in the baking and brewing industries and always used for the preparation of probiotics, especially its subtype, Saccharomyces boulardii, to prevent and treat various diarrhea and intestinal diseases. However, case reports on the side effects of a wide range of serious infections for the elderly, immunocompromised and critically ill patients after treatment with the S. cerevisiae have been increasing in recent years. The existing diagnose methods of the invasive S. cerevisiae infections in clinical, especially, the key step of the method-cell isolation, is time-consuming that always miss timey diagnose and early prevention. Here, we propose a new automatic micromanipulation method to label-free rapid isolation of S. cerevisiae based on the optically-induced dielectrophoresis (ODEP) technology, combining with image processing and recognition. S. cerevisiae is firstly identified by the image recognition method and then, automatically captured and moved to the target location by designing optical patterns. The results indicate the method can flexibly and automatically manipulate multiple S. cerevisiae cells simultaneously, such as, arranging S. cerevisiae cells, moving an array of the cells at any directions, aggregating the cells, and separating S. cerevisiae from the solution mixed with impurities. This work represents a step toward the use of automatic micromanipulation of ODEP technology to automatically and rapidly isolate S. cerevisiae for the detection of the invasive S. cerevisiae infections.

Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.

Oxidative Stress Response in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a Gram-negative environmental and human opportunistic pathogen highly adapted to many different environmental conditions. It can cause a wide range of serious infections, including wounds, lungs, the urinary tract, and systemic infections. The high versatility and pathogenicity of this bacterium is attributed to its genomic complexity, the expression of several virulence factors, and its intrinsic resistance to various antimicrobials. However, to thrive and establish infection, P. aeruginosa must overcome several barriers. One of these barriers is the presence of oxidizing agents (e.g., hydrogen peroxide, superoxide, and hypochlorous acid) produced by the host immune system or that are commonly used as disinfectants in a variety of different environments including hospitals. These agents damage several cellular molecules and can cause cell death. Therefore, bacteria adapt to these harsh conditions by altering gene expression and eliciting several stress responses to survive under oxidative stress. Here, we used PubMed to evaluate the current knowledge on the oxidative stress responses adopted by P. aeruginosa. We will describe the genes that are often differently expressed under oxidative stress conditions, the pathways and proteins employed to sense and respond to oxidative stress, and how these changes in gene expression influence pathogenicity and the virulence of P. aeruginosa. Understanding these responses and changes in gene expression is critical to controlling bacterial pathogenicity and developing new therapeutic agents.

High Carbapenem Resistance Caused by VIM and NDM Enzymes and OprD Alteration in Nonfermenter Bacteria Isolated from a Libyan Hospital.

Acinetobacter baumannii and Pseudomonas aeruginosa are among the most prevalent pathogens causing a wide range of serious infections in hospitalized patients and contaminating intensive care units and inanimate surfaces. The purpose of this study was to investigate the mechanism of carbapenem resistance in clinical and hospital environmental isolates of A. baumannii and P. aeruginosa recovered from a Libyan hospital. From a total of 82 Gram-negative bacteria, 8 isolates of A. baumannii and 3 isolates of P. aeruginosa exhibited resistance to imipenem with minimum inhibitory concentrations ranging from 16 to >32 μg/mL. Five isolates of A. baumannii harbored blaOXA-23 gene, from which three isolates were collected from patients and two from hospital environment. Only one isolate harbored blaNDM-1 gene, which was responsible for carbapenem resistance in A. baumannii. The OprD gene seems to be disturbed by an insertion sequence (IS) in two isolates and affected by polymorphism in one isolate. Pulsed-field gel electrophoresis results showed high genetic diversity among carbapenemase producing A. baumannii. This study highlights the dissemination of blaOXA-23 and blaNDM-1 genes in a Libyan setting. Therefore, infection prevention and control practices, antimicrobial stewardship initiatives, and antimicrobial resistance surveillance systems should be implemented to prevent the wide spread of antimicrobial resistance.

Repurposing disulfiram to target infections caused by non-tuberculous mycobacteria.

Non-tuberculous mycobacteria are emerging pathogens of significant worldwide interest because they have inherent drug resistance to a wide variety of FDA-approved drugs and cause a broad range of serious infections. In order to identify new drugs active against non-tuberculous mycobacteria, we identified disulfiram, utilized for treatment of alcohol dependence, as exhibiting potent growth-inhibitory activity against non-tuberculous mycobacteria. Whole-cell growth inhibition assays were used to screen and identify novel inhibitors. The hit compounds were tested against Vero cells to determine the selectivity index, and this was followed by determining time-kill kinetics against Mycobacterium fortuitum and Mycobacterium abscessus. Disulfiram's ability to synergize with several approved drugs utilized for the treatment of M. fortuitum and M. abscessus was determined using fractional inhibitory concentration indexes followed by determining its ability to reduce mycobacterial infections ex vivo. Finally, disulfiram's in vivo potential was determined in a neutropenic murine model mimicking mycobacterial infection. We identified disulfiram as possessing potent antimicrobial activity against non-tuberculous mycobacteria. Disulfiram exhibited concentration- and time-dependent bactericidal activity against M. fortuitum as well as against M. abscessus and synergized with all drugs utilized for their treatment. Additionally, disulfiram reduced bacterial load in macrophages in an intracellular killing assay better than amikacin. When tested in a murine neutropenic M. fortuitum infection model, disulfiram caused significant reduction in bacterial load in kidneys. Disulfiram exhibits all properties required for it to be repositioned as a novel anti-mycobacterial therapy and possesses a potentially new mechanism of action. Thus, it can be considered as a potent structural lead for the treatment of non-tuberculous mycobacterial infections.

Hierarchy of human IgG recognition within the Staphylococcus aureus immunome

Staphylococcus aureus is an opportunistic pathogen that causes a range of serious infections associated with significant morbidity, by strains increasingly resistant to antibiotics. However, to date all candidate vaccines have failed to induce protective immune responses in humans. We need a more comprehensive understanding of the antigenic targets important in the context of human infection. To investigate infection-associated immune responses, patients were sampled at initial presentation and during convalescence from three types of clinical infection; skin and soft tissue infection (SSTI), prosthetic joint infection (PJI) and pediatric hematogenous osteomyelitis (PHO). Reactivity of serum IgG was tested with an array of recombinant proteins, representing over 2,652 in-vitro-translated open reading frames (ORFs) from a community-acquired methicillin-resistant S. aureus USA300 strain. High-level reactivity was demonstrated for 104 proteins with serum IgG in all patient samples. Overall, high-level IgG-reactivity was most commonly directed against a subset of secreted proteins. Although based on limited surveys, we found subsets of S. aureus proteins with differential reactivity with serum samples from patients with different clinical syndromes. Together, our studies have revealed a hierarchy within the diverse proteins of the S. aureus “immunome”, which will help to advance efforts to develop protective immunotherapeutic agents.

Antimicrobial effects of Zingiber officinale extracts against multi-drug resistant Acinetobacter baumannii clinical isolates recovered from hospitalized patients in ICU

Zingiber officinale as an herbal medicinal plant is used for its potential antimicrobial activity against different microbial pathogens. Multi-drug resistant Acinetobacter baumannii as an important nosocomial pathogen especially in intensive care units is responsible for a wide range of serious infections in humans. The purpose of this study was to investigate the antimicrobial activity of Z. officinale extracts on growth of A. baumannii strains isolated from hospitalized patients in intensive care units in Tehran, Iran. During a 9 month study, 50 multi-drug resistant A. baumannii isolates were recovered from patients in ICU. The Kirby-Bauer disk diffusion method was used to determine resistance patterns of Multi-drug resistant A. baumannii isolates to antimicrobial agents. Micro-broth dilution method was used to determine the antimicrobial activity of methanol, acetone, and chloroform extracts of Z. officinale against multi-drug resistant A. baumannii isolates. The results of susceptibility testing showed that all the isolates were resistant to ceftriaxone, ciprofloxacin, ceftazidime, cefotaxime, cefepime and piperacillin. Resistance to colistin was found to be low (4%) and exhibited good antibacterial activity against tested isolates. This study’s findings revealed that methanol, acetone, and chloroform extracts of Z. officinale have anti-bacterial activity against tested bacterial isolates. Based on the results, the chloroform extracted fraction showed the highest level of activity at a minimal inhibitory concentration of 25 mg/ml on multi-drug resistant A. baumannii (64%). The minimal inhibitory concentration of ginger extract was as low as 3.2 mg/ml. The present study indicated that Z. officinale extracts, at various concentrations could be used as an antibacterial agent for treatment of patients in ICUs.

Evaluation of MinION nanopore sequencing for rapid enterovirus genotyping

Enteroviruses (EV) are associated with a range of serious infections, including aseptic meningitis, hand foot and mouth disease, myocarditis, acute flaccid paralysis and encephalitis. Improved methods for assessing EV genotypic diversity could assist molecular epidemiology studies, clinical diagnosis and environmental surveillance. We report new methods for EV genome amplification, and subsequent genotyping using the miniaturised MinION sequencing device. Importantly, this next-generation sequencer enabled correct strain-level assignment of identity for the EV-A71 isolate assessed, where strains with up to 99.7% similarity were discriminated. In addition, an accurate consensus sequence was produced for EV-A71 isolate RNA, with 99.3–99.6% similarity to the reference sequence. Thus, the long nanopore reads enabled rapid whole genome sequencing and strain level identification of EV- A71 isolate RNA. We also demonstrated potential for using MinION sequencing for direct detection of EV in water samples, which may have application for diversity analysis, water quality monitoring, and environmental surveillance.

Rothia mucilaginosa Bacteremia and Subsequent Typhlitis in a Patient With Acute Myeloid Leukemia

Abstract Rothia mucilaginosa is a gram-positive coccobacilli that is part of the normal flora of the human oropharynx and upper respiratory tract. Rothia spp. cause a wide range of serious infections, especially in immunocompromised hosts. We report a 54-year-old man with acute myelogenous leukemia, who recently had gingivitis and tooth extraction in preparation for bone marrow transplant evaluation. After receiving induction chemotherapy with cladribine, cytarabine, filgrastim, and mitoxantrone, he developed an upper gingival ulceration and subsequent Rothia mucilaginosa bacteremia on day 15 of hospitalization. He remained neutropenic on broad-spectrum antimicrobials and had intermittent breakthrough fevers. On day 17, he developed abdominal pain and was subsequently diagnosed with neutropenic enterocolitis. Despite broad-spectrum antibiotics, he died with sepsis and multiorgan failure.

The underlying mechanisms of genetic innovation and speciation in the family Corynebacteriaceae: A phylogenomics approach

The pangenome of a bacterial species population is formed by genetic reduction and genetic expansion over the long course of evolution. Gene loss is a pervasive source of genetic reduction, and (exogenous and endogenous) gene gain is the main driver of genetic expansion. To understand the genetic innovation and speciation of the family Corynebacteriaceae, which cause a wide range of serious infections in humans and animals, we analyzed the pangenome of this family, and reconstructed its phylogeny using a phylogenomics approach. Genetic variations have occurred throughout the whole evolutionary history of the Corynebacteriaceae. Gene loss has been the primary force causing genetic changes, not only in terms of the number of protein families affected, but also because of its continuity on the time series. The variation in metabolism caused by these genetic changes mainly occurred for membrane transporters, two-component systems, and metabolism related to amino acids and carbohydrates. Interestingly, horizontal gene transfer (HGT) not only caused changes related to pathogenicity, but also triggered the acquisition of antimicrobial resistance. The Darwinian theory of evolution did not adequately explain the effects of dispersive HGT and/or gene loss in the evolution of the Corynebacteriaceae. These findings provide new insight into the evolution and speciation of Corynebacteriaceae and advance our understanding of the genetic innovation in microbial populations.

Staphylococcus aureus: Current State of Prevalence, Impact, and Vaccine Development.

Staphylococcus aureus is a fastidious pathogen of global concern. S. aureus can not only cause a wide range of serious infections, but can also colonize healthy individuals. Nosocomial- associated S. aureus infection is a major concern for healthcare facilities. Recent increases in antibiotic resistance and community-acquired infection highlight the need for improved understanding for prevention and treatment of this pathogen. This minireview addresses the current state of S. aureus prevalence, correlates of immunity, and vaccine development.

Eravacycline (TP-434) is efficacious in animal models of infection.

Eravacycline is a novel broad-spectrum fluorocycline antibiotic being developed for a wide range of serious infections. Eravacycline was efficacious in mouse septicemia models, demonstrating 50% protective dose (PD50) values of ≤ 1 mg/kg of body weight once a day (q.d.) against Staphylococcus aureus, including tetracycline-resistant isolates of methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes. The PD50 values against Escherichia coli isolates were 1.2 to 4.4 mg/kg q.d. In neutropenic mouse thigh infection models with methicillin-sensitive S. aureus (MSSA) and S. pyogenes, eravacycline produced 2 log10 reductions in CFU at single intravenous (i.v.) doses ranging from 0.2 to 9.5 mg/kg. In a neutropenic mouse lung infection model, eravacycline administered i.v. at 10 mg/kg twice a day (b.i.d.) reduced the level of tetracycline-resistant MRSA in the lung equivalent to that of linezolid given orally (p.o.) at 30 mg/kg b.i.d. At i.v. doses of 3 to 12 mg/kg b.i.d., eravacycline was more efficacious against tetracycline-resistant Streptococcus pneumoniae in a neutropenic lung infection model than linezolid p.o. at 30 mg/kg b.i.d. Eravacycline showed good efficacy at 2 to 10 mg/kg i.v. b.i.d., producing up to a 4.6 log10 CFU reduction in kidney bacterial burden in a model challenged with a uropathogenic E. coli isolate. Eravacycline was active in multiple murine models of infection against clinically important Gram-positive and Gram-negative pathogens.

Cephalosporin side chain idiosyncrasies: a case report of ceftriaxone-induced agranulocytosis and review of literature.

Drug-induced neutropenia is characterized by a sharp decrease in the absolute neutrophil count (ANC) to <500/mm3; agranulocytosis is said to be present once the granulocyte count reaches zero. Although associated with a large variety of drugs, this adverse effect is rare, occurring in 2.4–15.4 cases per million courses of therapy [1]. Because of its efficacy and relative safety, ceftriaxone is commonly used for treating a broad range of serious infections [2]. In this report, we describe a patient who developed agranulocytosis during treatment with ceftriaxone and recovered after treatment was changed to cefepime, and we review previously reported cases of ceftriaxone-induced agranulocytosis.

Rothia bacteremia: a 10-year experience at Mayo Clinic, Rochester, Minnesota.

Rothia spp. are Gram-positive cocco-bacilli that cause a wide range of serious infections, especially in immunocompromised hosts. Risk factors for Rothia mucilaginosa (previously known as Stomatococcus mucilaginosus) bacteremia include prolonged and profound neutropenia, malignancy, and an indwelling vascular foreign body. Here, we describe 67 adults at the Mayo Clinic in Rochester, MN, from 2002 to 2012 with blood cultures positive for Rothia. Twenty-five of these patients had multiple positive blood cultures, indicating true clinical infection. Among these, 88% (22/25) were neutropenic, and 76% (19/25) had leukemia. Common sources of bacteremia were presumed gut translocation, mucositis, and catheter-related infection. One patient died with Rothia infection. Neutropenic patients were less likely to have a single positive blood culture than were nonneutropenic patients. Antimicrobial susceptibility testing was performed on 21% of the isolates. All of the tested isolates were susceptible to vancomycin and most beta-lactams; however, four of six tested isolates were resistant to oxacillin. There was no difference between the neutropenic and nonneutropenic patients in need of intensive care unit care, mortality, or attributable mortality.

Improved protective efficacy of a chimeric Staphylococcus aureus vaccine candidate iron‐regulated surface determinant B (N126–P361)‐target of RNAIII activating protein in mice

The pathogen Staphylococcus aureus causes a wide range of serious infections, necessitating urgent development of a vaccine against this organism. However, currently developed vaccines are relatively ineffective because of the limited antigenic component that is contained in the vaccine formulations. To develop an effective S. aureus candidate vaccine, overlapping PCR was used to add the truncated immunodominant antigen iron-regulated surface determinant B (IsdB)(N126-P361) (tIsdB) to the N-terminal of intact antigen target of RNAIII activating protein (TRAP) and thus construct a tIsdB-TRAP chimera. The humoral and cellular immune responses against tIsdB-TRAP were compared with those against single or combined formulations. tIsdB-TRAP elicited significantly stronger humoral responses in mice (P < 0.05). As to cellular immune responses in mice, the tIsdB-TRAP group resulted in a greater IL-4 response than did other groups (P < 0.05). Greater amounts of IL-2 and IFN-γ were found in the tIsdB-TRAP group. Mouse challenge also showed that tIsdB-TRAP provided better protection against S. aureus than did the control groups. These results suggest that this chimeric protein may be a promising pathogen target for further vaccine development.

Scedosporium aurantiacumis as virulent asS. prolificans, and shows strain-specific virulence differences, in a mouse model

Several Scedosporium species are clinically important emerging pathogens. Scedosporium prolificans is reported to be the most virulent of the species, while the recently described species Scedosporium aurantiacum, which accounts for a substantial proportion of Australian clinical isolates is capable of causing a range of serious infections. In addition, environmental surveys have revealed a high prevalence of S. aurantiacum in the urban Sydney region. This study was conducted to assess the virulence of selected S. aurantiacum strains recovered from patients who are colonized or have invasive disease, as well as those from environmental sources, in comparison with S. prolificans. PCR fingerprinting with the primer M13 revealed high genetic variation among the S. aurantiacum strains. We evaluated the virulence of eight S. aurantiacum and two S. prolificans strains in a murine model using an infectious dose of 2 × 10⁵ conidia. S. aurantiacum was noted to be as virulent as S. prolificans, causing death in 60-100% of mice (P > 0.05). There were significant strain-specific virulence differences (P < 0.005), indicating a possible link between genotype and virulence in S. aurantiacum.

Meropenem

Meropenem (Merrem, Meronem) is a broad-spectrum antibacterial agent of the carbapenem family, indicated as empirical therapy prior to the identification of causative organisms, or for disease caused by single or multiple susceptible bacteria in both adults and children with a broad range of serious infections. Meropenem is approved for use in complicated intra-abdominal infection (cIAI), complicated skin and skin structure infection (cSSSI) and bacterial meningitis (in paediatric patients aged > or = 3 months) in the US, and in most other countries for nosocomial pneumonia, cIAI, septicaemia, febrile neutropenia, cSSSI, bacterial meningitis, complicated urinary tract infection (UTI), obstetric and gynaecological infections, in cystic fibrosis patients with pulmonary exacerbations, and for the treatment of severe community-acquired pneumonia (CAP). Meropenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae. It has similar efficacy to comparator antibacterial agents, including: imipenem/cilastatin in cIAI, cSSSI, febrile neutropenia, complicated UTI, obstetric or gynaecological infections and severe CAP; clindamycin plus tobramycin or gentamicin in cIAI or obstetric/gynaecological infections; cefotaxime plus metronidazole in cIAI; cefepime and ceftazidime plus amikacin in septicaemia or febrile neutropenia; and ceftazidime, clarithromycin plus ceftriaxone or amikacin in severe CAP. Meropenem has also shown similar efficacy to cefotaxime in paediatric and adult patients with bacterial meningitis, and to ceftazidime when both agents were administered with or without tobramycin in patients with cystic fibrosis experiencing acute pulmonary exacerbations. Meropenem showed greater efficacy than ceftazidime or piperacillin/tazobactam in febrile neutropenia, and greater efficacy than ceftazidime plus amikacin or tobramycin in patients with nosocomial pneumonia. Meropenem is well tolerated and has the advantage of being suitable for administration as an intravenous bolus or infusion. Its low propensity for inducing seizures means that it is suitable for treating bacterial meningitis and is the only carbapenem approved in this indication. Thus, meropenem continues to be an important option for the empirical treatment of serious bacterial infections in hospitalized patients.