Paul G Higgins

University of Cologne | UOC · Institute for Medical Microbiology, Immunology and Hygiene

Purpose To analyse recent epidemiological trends of bloodstream infections (BSI) caused by Enterococcus spp. In adult patients admitted to tertiary care centres in Germany. Methods Epidemiological data from the multicentre R-NET study was analysed. Patients presenting with E. faecium or E. faecalis in blood cultures in six German tertiary care uni...

Background Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, whi...

An offspring of BA.2.86, JN.1, is now the most widely circulating variant of SARS-CoV-2 globally. JN.1 displayed significantly enhanced immune escape compared to BA.2.86 with 2.1-fold decrease in 50% neutralization titres (NT50).1 In the post-pandemic phase, clinical surveillance of SARS-CoV-2 variants has been limited due to a notable decrease in...

Infections caused by carbapenem-resistant Acinetobacter baumannii are a global threat causing a high number of fatal infections. This microorganism can also easily acquire antibiotic resistance determinants, making the treatment of infections a big challenge, and has the ability to persist in the hospital environment under a wide range of condition...

Objectives To analyse recent epidemiological trends of bloodstream infections (BSI) caused by Enterococcus spp. In adult patients admitted to tertiary care centres in Germany. Methods Epidemiological data from the multicentre R-NET study was analysed. Patients presenting with E. faecium or E. faecalis in blood cultures in six German tertiary care...

This study investigated the potential of using SARS-CoV-2 viral concentrations in dust as an additional surveillance tool for early detection and monitoring of COVID-19 transmission. Dust samples were collected from 8 public locations in 16 districts of Bangkok, Thailand, from June to August 2021. SARS-CoV-2 RNA concentrations in dust were quantifi...

The natural reservoirs of the nosocomial pathogen Acinetobacter baumannii are not well defined. We previously identified white storks as a model system to study the ecology of A. baumannii . Having screened more than 1,300 white stork nestlings over a period of six years across different regions of Poland and Germany (overall isolation rate of ∼29....

Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiv...

To give an update on the molecular epidemiology and global distribution of carbapenemase encoding genes, we subjected 313 carbapenem-resistant Acinetobacter baumannii isolated from 114 study centers in 47 countries in five world regions, Africa, Asia, Europe, Latin America, and North America, to whole genome sequencing. Numbers of isolates investig...

Acinetobacter baumannii is a globally distributed human pathogen. Infections caused by carbapenem-resistant isolates of A. baumannii (CRAB) are of great concern, as treatment options are very limited. Despite having among the highest rates reported worldwide, there exists limited genomic data from CRAB strains isolated in the Middle East. Here we r...

As SARS-CoV-2 evolves, emerging variants such as BA.2.86 raise public health concerns and challenge existing control measures due to the potential for increased transmissibility and immune escape. By late July, 2023, a number of countries had detected BA.2.86. On Aug 17, 2023, it was classified as a variant under surveillance by WHO due to its sign...

Highlight High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for MPXV DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines, and therapeu...

Background: Cefiderocol is a novel siderophore cephalosporin with potent activity against multi-drug-resistant Gram-negative pathogens including carbapenem-resistant Acinetobacter baumannii (CRAB). Methods: The susceptibility of 313 non-duplicate CRAB isolates with defined carbapenem resistance mechanisms from a global collection to cefiderocol, ce...

Type 4 pili (T4P) are multifunctional filaments involved in adhesion, surface motility, colony formation, and horizontal gene transfer. These extracellular polymers are surface-exposed and, therefore, act as antigens. The human pathogen Neisseria gonorrhoeae uses pilin antigenic variation to escape immune surveillance, yet it is unclear how antigen...

Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be addressed urgently. Here, we explored a Ca-EDTA combination with Aztreonam or Ceftazidime-Avibactam in vitro and in vivo against diverse CPKp clinical isolates. The synergy testing of this study demonstr...

Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited due to economic and technical reasons. In this study, wastewater samples were colle...

Antimicrobial resistance poses a global threat to public health. Of great concern are Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales with resistance to carbapenems or third-generation cephalosporins. The aim of the present study was to investigate the in vitro activity of the novel siderophore cephaloporin cefiderocol (CID) an...

Objectives: This study aimed to characterise carbapenemase-producing Acinetobacter baumannii (A. baumannii) isolates from Danish patients using whole genome sequencing (WGS). It also compared typing and epidemiological data for further investigation of the spread and origin of the carbapenemase-producing A. baumannii isolates. Methods: From 1 Ja...

Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform...

The objective of the study was to assess the prevalence and molecular epidemiology of EBSL/Carbapenemase-producing Klebsiella pneumoniae isolates causing healthcare-associates bateraemia of urinary origin in Spain

Introduction. Acinetobacter baumannii infections can be extremely challenging to treat owing to the worldwide prevalence of multidrug-resistant isolates, especially against carbapenems. Colonization with carbapenem-resistant A. baumannii (CRAb) requires rapid action from an infection control perspective because the organism is known for its propens...

Acinetobacter baumannii is especially known as a cause of nosocomial infections worldwide. It shows intrinsic and acquired resistances to numerous antimicrobial agents, which can render the treatment difficult. In contrast to the situation in human medicine, there are only few studies focusing on A. baumannii among livestock. In this study, we have...

The emergence and global expansion of hyper-virulent and multidrug resistant (MDR) Klebsiella pneumoniae is an increasing healthcare threat worldwide. The epidemiology of MDR K. pneumoniae is under-characterized in many parts of the world, particularly Africa. In this study, K. pneumoniae isolates from hospitals in Khartoum, Sudan, have been whole-...

Objectives: To characterize the genetic environment of metallo-β-lactamases (MBL) in carbapenem-resistant clinical Acinetobacter pittii isolates. Methods: Seventeen carbapenem-resistant A. pittii isolates harbouring an MBL were collected between 2010 and 2015 in Germany. Antimicrobial susceptibility testing was performed using agar dilution. Pre...

Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is a WHO priority 1 critical pathogen. Despite Israel being affected early by high CRAb rates, limited molecular data are available. We investigated the presence of carbapenemases among 198 Acinetobacter spp. clinical isolates from Israel between 2001 and 2006. Methods Strains from 3 a...

Darobactins bind to the novel antibiotic target BamA in the outer membrane BAM‐complex of Gram‐negative pathogens. The renewal of the outer membrane proteins is prevented and bacteria are lysed. The new derivative D22 was created through cryo‐EM structure‐ and activity‐guided biosynthetic engineering as described by Thomas Marlovits, Jennifer Herrm...

Darobactins bind to the novel antibiotic target BamA in the outer membrane BAM‐complex of Gram‐negative pathogens. The renewal of the outer membrane proteins is prevented and bacteria are lysed. The new derivative D22 was created through cryo‐EM structure‐ and activity‐guided biosynthetic engineering as described by Thomas Marlovits, Jennifer Herrm...

Objectives Assessment of vancomycin-resistant Enterococcus faecium (VREfm) prevalence upon hospital admission and analysis of risk factors for colonisation. Methods From 2014-2018, patients were recruited within 72 hours of admission to seven participating German university hospitals, screened for VREfm and questioned for potential risk factors (p...

This study is a first report on the identification of multidrug-resistant (MDR) Acinetobacter bereziniae among non-baumannii acinetobacters that had previously escaped automated laboratory detection, and characterize their clinical courses of infection at two tertiary-care hospitals in Shenzhen city, China (2015-2017). Herein, definitive identifica...

Colistin (polymyxin E) is increasingly used as a last-resort antibiotic for the treatment of severe infections with multidrug-resistant Gram-negative bacteria. In contrast to human medicine, colistin is also used in veterinary medicine for metaphylaxis. Our objective was to decipher common colistin resistance mechanisms in Klebsiella pneumoniae iso...

Bacterial efflux pumps are among the key mechanisms of resistance against antibiotics and biocides. We investigated whether differential expression levels of the RND-type efflux pumps AdeABC and AdeIJK impacted the susceptibility to commonly used biocides in multidrug-resistant Acinetobacter baumannii. Susceptibility testing and time–kill assays of...

The aim of this study was to investigate and compare the molecular epidemiology and carbapenem resistance determinants in clinical Acinetobacter baumannii isolates collected in Germany during four multicentre surveillance studies conducted by the Paul-Ehrlich-Society for Infection Therapy in 2010, 2013, 2016 and 2019.Isolates were collected prospec...

We studied a novel taxon of the genus Acinetobacter , which comprised six strains collected in Czechia, Germany, Indonesia and Turkey between 2015 and 2021. The organisms were isolated from environmental soil, water samples and cow faeces. Their genome sizes varied between 3.3 and 3.5 Mb, with a G+C content of 40.4–40.8 mol%. Based on genus-wide co...

Over recent decades, the pipeline of antibiotics acting against Gram‐negative bacteria is running dry, as most discovered candidate antibiotics suffer from insufficient potency, pharmacokinetic properties, or toxicity. The darobactins, a promising new small peptide class of drug candidates, bind to novel antibiotic target BamA, an outer membrane pr...

Over recent decades, the pipeline of antibiotics acting against Gram‐negative bacteria is running dry, as most discovered candidate antibiotics suffer from insufficient potency, pharmacokinetic properties, or toxicity. The darobactins, a promising new small peptide class of drug candidates, bind to novel antibiotic target BamA, an outer membrane pr...

The monkeypox virus is excreted in the feces of infected individuals. Therefore, there is an interest in using viral load detection in wastewater for sentinel early surveillance at a community level and as a complementary approach to syndromic surveillance. We collected wastewater from 63 sewered and non-sewered locations in Bangkok city center bet...

Over recent decades, the pipeline of antibiotics acting against Gram-negative bacteria is running dry, as most discovered candidate antibiotics suffer from insufficient potency, pharmacokinetic properties, or toxicity. The darobactins, a promising new small peptide class of drug candidates, bind to novel antibiotic target BamA, an outer membrane pr...

To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016–2019). Also collected were 3GCR/CR and s...

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The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp). Our study demonstrated the rising trend of ColRkp showing extensively and pand...

Over recent decades, the pipeline of antibiotics acting against Gram-negative bacteria is running dry, as most discovered candidate antibiotics suffer from insufficient potency, pharmacokinetic properties, or toxicity. Darobactins, a recently discovered class of peptide antibiotics, belong to the most promising drug candidates, binding to a new tar...

Overcoming colistin-resistant Acinetobacter baumannii (CoR-AB) has become a major concern due to the lack of effective antibiotics. This study aimed to explore the prevalence of CoR-AB clinical isolates in Thailand, their mechanisms of resistance, and test the efficacy of colistin plus sulbactam against CoR-AB isolates. The colistin resistance rate...

Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is a WHO priority 1 critical pathogen. Despite early emergence of elevated CRAb rates in Israel, limited molecular data from this location are available. We searched for carbapenemases among 198 clinical Acinetobacter spp. from Israel between 2001 and 2006. Methods Strains from 3 archi...

Objectives To describe the propensity of carbapenem-resistant Pseudomonas aeruginosa to spread within a hospital critical care setting. Methods The study was conducted in a 700-bed tertiary centre in Cologne, Germany. P. aeruginosa resistant to piperacillin, ceftazidime, cefepime, imipenem, meropenem and ciprofloxacin, isolated from clinical and s...

Introduction . Carbapenem-resistant Acinetobacter baumannii (CRAB) is the primary pathogen causing hospital-acquired infections. The spread of CRAB is mainly driven by the dissemination of resistant clones, and in Latin America, International Clones IC-1 (also known as clonal complex CC1), IC-4 (CC15) and IC-5 (CC79) are the most prevalent. Gap Sta...

We investigated a taxonomically novel group of the genus Acinetobacter , which included five strains isolated from soil and water samples collected in preserved forest areas in Czechia between 2013 and 2021. The whole-genome sequences of the strains were 3.1–3.2 Mb in size, with G+C contents of 38.0–38.2 mol%. Core genome-based phylogenetic analysi...

Background The old antimicrobial nitroxoline is currently repurposed for oral treatment of uncomplicated urinary tract infections (UTIs). Objectives To investigate the in vitro activity of nitroxoline against carbapenem-resistant Acinetobacter baumannii (CRAb). Methods From an international collection of previously well-characterized clinical A....

The spread of antibiotic-resistant Acinetobacter baumannii poses a significant threat to public health worldwide. This nosocomial bacterial pathogen can be associated with life-threatening infections, particularly in intensive care units. A. baumannii is mainly described as an extracellular pathogen with restricted survival within cells. This study...

Background The burden of bloodstream infections remains high worldwide and cannot be confined to short-term in-hospital mortality. We aimed to develop scores to predict short-term and long-term mortality in patients with bloodstream infections. Methods The Bloodstream Infection due to Multidrug-resistant Organisms: Multicenter Study on Risk Factor...

Background Evidence supporting the effectiveness of single-room contact precautions (SCP) in preventing in-hospital acquisition of vancomycin-resistant enterococci (haVRE) is limited. Aim We assessed the impact of SCP on haVRE and their transmission. Methods We conducted a prospective, multicentre cohort study in German haematological/oncological...

Background Rapid emergence of global azithromycin resistance, with ceftriaxone reduce susceptibility/resistant strains, threatens the current recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment. Thailand is a major risk area for gonorrhea because it as a key destination for sex tourism industry, whe...

Background Due to the increase in multi-drug resistance (MDR) of Acinetobacter baumannii chronic infections with accompanying considerable morbidity and mortality, it is imperative to find effective novel treatments. Durlobactam (DUR) is a potent broad-spectrum inhibitor of Ambler classes A, C and D serine β-lactamases that effectively restores sul...

To understand the reasons of successful spread of carbapenem-resistant Klebsiella pneumoniae ST14 (CRKP-ST14) in countries of the Arabian Peninsula, the resistome, capsular locus, carbapenemase carrying plasmid types, and core genome of isolates from the region were compared to global isolates. Thirty-nine CRKP-ST14 strains isolated from 13 hospita...

Staphylococcus aureus represents a serious infectious threat to global public health and a vaccine against S. aureus represents an unmet medical need. We here characterise two S. aureus vaccine candidates, coproporphyrinogen III oxidase (CgoX) and triose phosphate isomerase (TPI), which fulfil essential housekeeping functions in heme synthesis and...

Colistin resistance rates among Acinetobacter baumannii clinical isolates have increased over the last 20 years. Despite reports of the spread of plasmid-mediated colistin resistance among Enterobacterales , the presence of mcr -type genes in Acinetobacter spp. remains rare, and reduced colistin susceptibility is mainly associated with the acquisit...

The active efflux of antimicrobials by bacteria can lead to antimicrobial resistance and persistence and can affect multiple different classes of antimicrobials. Efflux pumps are tightly regulated, and their overexpression can be mediated by changes in their regulators.

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in v...

The global rapid emergence of azithromycin/ceftriaxone resistant Neisseria gonorrhoeae threatens current recommend azithromycin/ceftriaxone dual therapy for gonorrhea to ensure effective treatment. Here, we identified the first two N. gonorrhoeae isolates with decreased ceftriaxone susceptibility in Thailand. Among 134 N. gonorrhoeae isolates colle...

The study was performed to provide an overview of the molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in Afghanistan isolated by the German military medical service during the Afghanistan conflict. A total of 18 isolates were collected between 2012 and 2018 at the microbiological laboratory of the field hospital in Camp Marma...

Background: Meningitis and spinal infections with Gram-negative bacteria after local injections for treatment of chronic back pain are rare. This study investigated an outbreak of Pseudomonas aeruginosa infections following computed tomography (CT)-guided spinal injections (SI). Methods: A case was defined as a spinal infection or meningitis with...

The Acinetobacter baumannii RND efflux pump AdeABC is regulated by the 2-component regulator AdeRS. In this study, we compared regulation and expression of AdeABC of the reference strains ATCC 17978 and ATCC 19606. A clearly stronger efflux activity was demonstrated for ATCC 19606. An amino acid substitution at residue 172 of adeS was identified as...

We investigated the molecular epidemiology of 21 carbapenem-resistant A. baumannii from Libya, and assessed their relative fitness. Core-genome MLST revealed five inter-hospital transmission clusters. Three clusters were associated with the international clones (IC) IC1, IC2, and IC7. Carbapenem-resistance was associated with blaOXA-23,blaGES-11, o...

Acinetobacter baumannii is an important pathogen in hospital acquired infections. Although tigecycline currently remains a potent antibiotic for treating infections caused by multidrug resistant A. baumannii (MDRAB) strains, reports of tigecycline resistant isolates have substantially increased. The resistance mechanisms to tigecycline in A. bauman...

Rationale Steroid refractory graft‐vs‐host disease (sr‐GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo‐HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM...

This study aimed to define the taxonomic position and structure of a novel, taxonomically unique group of 26 Acinetobacter strains, provisionally designated Taxon 24 (T24). The strains were recovered from soil and freshwater ecosystems (n=21) or animals (n=5) in Czechia, Scotland, Germany, the Netherlands and Turkey between 1993 and 2015. They were...

The spread of antibiotic resistant Acinetobacter baumannii poses a significant threat to public health worldwide. This nosocomial bacterial pathogen can be associated with life-threatening infections, particularly in intensive care units. A. baumannii is mainly described as an extracellular pathogen with restricted survival within cells. This study...

Objectives To determine the most common tigecycline resistance mechanisms in carbapenem-resistant Acinetobacter baumannii isolates obtained during the global Tigecycline Evaluation Surveillance Trial (TEST). Methods Tigecycline MICs were determined by broth microdilution. WGS was used to screen for the previously identified tigecycline resistance...

At the Bundeswehr Hospitals of Hamburg and Westerstede, patients repatriated from subtropical war and crisis zones of Northern Africa and the Middle East were medically treated, including microbiological assessment. Within a six-year interval, 16 Acinetobacter spp. strains, including 14 Acinetobacter baumannii (Ab) isolates with resistance against...

Carbapenem resistant Acinetobacter baumannii (CRAb) is an important global pathogen contributing to increased morbidity and mortality in hospitalized patients, due to limited alternative treatment options. Nine international clonal (IC) lineages have been identified in many countries worldwide, however, data still lacks from some parts of the world...

Introduction. Gram-negative bacteria are a common source of infection both in hospitals and in the community, and antimicrobial resistance is frequent among them, making antibiotic therapy difficult, especially when these isolates carry carbapenem resistance determinants. Hypothesis/Gap Statement . A simple method to detect all the commonly found c...

Objectives To characterize two Enterococcus faecium isolates with different resistance phenotypes obtained from the same blood culture. Methods The isolates were identified by MALDI-TOF MS and antimicrobial susceptibility testing (AST) was performed using a VITEK® 2 AST P592 card and Etest. WGS was performed on the MiSeq and MinION sequencer platf...

Purpose The rise of carbapenem-resistant A. baumannii (CRAB) is considered a public health problem limiting the treatment options. Our current work studied the emergence and mechanisms of colistin-resistance among CRAB isolates in Egypt. Materials and Methods Seventeen clinically recovered A. baumannii were identified and screened for their antimi...

The aim of this study was to determine the activity and synergistic mechanisms of resveratrol in combination with chlorhexidine against carbapenem-resistant Acinetobacter baumannii clinical isolates. The activity of resveratrol plus antimicrobial agents was determined by checkerboard and time-kill assay against carbapenem-resistant A . baumannii is...

Carbapenem-resistant Acinetobacter baumannii (CRAB) are emerging worldwide. In South America, clinical isolates presenting such a phenotype usually do not belong to the globally distributed international clone 2 (IC2). The majority of these isolates are also resistant to multiple other antimicrobials and are often designated extremely drug-resistan...

The objective of this study was the phenotypic and genotypic characterization of a carbapenem resistant Acinetobacter baumannii (CRAB) isolate. The isolate, recovered in Northern Spain in 2019, was identified by MALDI-TOF to the species level. Antimicrobial susceptibility testing was performed using the Phoenix BD NMIC-502 Panel, E-test, and broth...

Objective: Acinetobacter baumannii has emerged as a problematic hospital pathogen and tigecycline is among the few remaining antibiotics retaining activity against multidrug-resistant A. baumannii. This study was aimed to elucidate the tigecycline resistance mechanisms in 28 unique clinical A. baumannii strains from nine provinces in China. Method...

Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms...

Successful treatment of Acinetobacter baumannii infections require early and appropriate antimicrobial therapy. One of the first steps in this process is understanding which β-lactamase (bla) alleles are present and in what combinations. Thus, we performed WGS on 98 carbapenem-resistant A. baumannii (CR Ab). In most isolates, an acquired blaOXA car...

Antimicrobial resistance (AMR) is a major global health threat that requires an interdisciplinary international approach to address. In response to calls from policymakers and funders alike, a growing number of research networks on AMR have been created with this approach in mind. However, there are many challenges facing researchers in establishin...