Antimicrobial susceptibility of bacterial uropathogens in a South African regional hospital

Background: Urinary tract infections are common bacterial infections affecting millions worldwide. Although treatment options for urinary tract infections are well established, with ciprofloxacin long considered one of the antibiotics of choice, increasing antibiotic resistance may delay the initiation of appropriate therapy. While this increase in antimicrobial resistance has been demonstrated in multiple studies around the world, there is a dearth of information from developing countries. Objective: This study aimed to describe the antimicrobial susceptibility patterns of commonly isolated bacterial uropathogens in a South African hospital. Methods: Antimicrobial susceptibility data of isolates obtained from urine specimens at the RK Khan Hospital, a regional hospital in KwaZulu-Natal, South Africa, between January 2018 and December 2020 were retrieved from the hospital’s laboratory information system and analysed to determine the differences in resistance rates between the most frequently isolated bacterial uropathogens. Results: Of the 3048 bacterial urinary pathogens isolated between 2018 and 2020, Escherichia coli (1603; 53%) was the most common, followed by Klebsiella spp. (437; 14%). Both E. coli and Klebsiella spp. showed high rates of resistance to amoxicillin/clavulanic acid (29.8% and 42.3%) and ciprofloxacin (37.7% and 30.4%). Nitrofurantoin resistance was low among E. coli (6.2%) but high among Klebsiella spp. (61.3%). Conclusion: E. coli and Klebsiella spp. in this study were highly resistant to amoxicillin/clavulanic acid and ciprofloxacin, two of the frequently prescribed oral treatment options. What this study adds: This study highlights the importance of regular local antimicrobial resistance surveillance to inform appropriate empiric therapy

Case-fatality and sequelae following acute bacterial meningitis in South Africa, 2016 through 2020

OBJECTIVES : Providing country-specific estimates of case fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress toward the World Health Organization's roadmap to “defeating meningitis by 2030”. METHODS : From 2016-2020, GERMS-SA conducted enhanced surveillance at 26 hospitals across South Africa. Episodes of laboratory-confirmed BM due to Streptococcus pneumoniae, Haemophilus influenzae , and Neisseria meningitidis were included. Risk factors for in-hospital death and sequelae at hospital discharge among survivors were analyzed. RESULTS : Of 12,717 invasive bacterial infections reported nationally, 39% (4980) were from enhanced surveillance sites, including 4159 pneumococcal, 640 H. influenzae , and 181 meningococcal infections. BM accounted for 32% (1319/4159) of pneumococcal, 21% (136/640) of H. influenzae , and 83% (151/181) of meningococcal invasive diseases. Clinical data were available for 91% (1455/1606) of BM: 26% (376/1455) were aged <5 years, 50% (726/1455) were female, and 62% (723/1171) with known HIV results, were HIV-infected. In-hospital case fatality was 37% (534/1455), and 24% (222/921) of survivors had adverse sequelae. Risk factors for death included altered mental status, HIV infection, and comorbidities. Risk factors for adverse sequelae included altered mental status and antimicrobial nonsusceptibility. CONCLUSION : BM in South Africa has a high case fatality, and adverse sequelae frequently occur among survivors. Those with comorbidities (including HIV) are at the highest risk.The NICD of the National Health Laboratory Service.http://www.elsevier.com/locate/ijidhj2023Medical Microbiolog

Effects of introducing Xpert MTB/RIF test on multi-drug resistant tuberculosis diagnosis in KwaZulu-Natal South Africa.

CAPRISA, 2014.Abstract available in pdf

Evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of Mycobacterium tuberculosis isolates from KwaZulu-Natal.

CAPRISA, 2015.Abstract available in pdf

Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

11 páginas, 2 figuras, 1 tablaInappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038)Peer reviewe

Failure of BACTEC™ MGIT 960™ to detect <i>Mycobacterium tuberculosis </i> complex within a 42-day incubation period

For the optimal recovery of Mycobacterium tuberculosis from the BACTEC™ Mycobacterium Growth Indicator Tube 960™ system, an incubation period of 42–56 days is recommended by the manufacturer. Due to logistical reasons, it is common practice to follow an incubation period of 42 days. We undertook a retrospective study to document positive Mycobacterium Growth Indicator Tube cultures beyond the 42-day incubation period. In total, 98/110 (89%) were positive for M. tuberculosis complex. This alerted us to M. tuberculosis growth detection failure at 42 days

Pyrazinamide phenotypic and genotypic drugs susceptibility results.

Pyrazinamide phenotypic and genotypic drugs susceptibility results.</p

Decreasing fluconazole susceptibility of clinical South African Cryptococcus neoformans isolates over a decade.

BackgroundFluconazole is used in combination with amphotericin B for induction treatment of cryptococcal meningitis and as monotherapy for consolidation and maintenance treatment. More than 90% of isolates from first episodes of cryptococcal disease had a fluconazole minimum inhibitory concentration (MIC) ≤4 μg/ml in a Gauteng population-based surveillance study of Cryptococcus neoformans in 2007-2008. We assessed whether fluconazole resistance had emerged in clinical cryptococcal isolates over a decade.Methodology and principal findingsWe prospectively collected C. neoformans isolates from 1 January through 31 March 2017 from persons with a first episode of culture-confirmed cryptococcal disease at 37 South African hospitals. Isolates were phenotypically confirmed to C. neoformans species-complex level. We determined fluconazole MICs (range: 0.125 μg/ml to 64 μg/ml) of 229 C. neoformans isolates using custom-made broth microdilution panels prepared, inoculated and read according to Clinical and Laboratory Standards Institute M27-A3 and M60 recommendations. These MIC values were compared to MICs of 249 isolates from earlier surveillance (2007-2008). Clinical data were collected from patients during both surveillance periods. There were more males (61% vs 39%) and more participants on combination induction antifungal treatment (92% vs 32%) in 2017 compared to 2007-2008. The fluconazole MIC50, MIC90 and geometric mean MIC was 4 μg/ml, 8 μg/ml and 4.11 μg/ml in 2017 (n = 229) compared to 1 μg/ml, 2 μg/ml and 2.08 μg/ml in 2007-2008 (n = 249) respectively. Voriconazole, itraconazole and posaconazole Etests were performed on 16 of 229 (7%) C. neoformans isolates with a fluconazole MIC value of ≥16 μg/ml; only one had MIC values of >32 μg/ml for these three antifungal agents.Conclusions and significanceFluconazole MIC50 and MIC90 values were two-fold higher in 2017 compared to 2007-2008. Although there are no breakpoints, higher fluconazole doses may be required to maintain efficacy of standard treatment regimens for cryptococcal meningitis

Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa

The largest global outbreak of extensively drug-resistant (XDR) tuberculosis (TB) was identified in Tugela Ferry, KwaZulu-Natal (KZN), South Africa in 2005. The antecedents and timing of the emergence of drug resistance in this fatal epidemic XDR outbreak are unknown, and it is unclear whether drug resistance in this region continues to be driven by clonal spread or by the development of de novo resistance. A whole genome sequencing and drug susceptibility testing (DST) was performed on 337 clinical isolates of Mycobacterium tuberculosis (M.tb) collected in KZN from 2008 to 2013, in addition to three historical isolates, one of which was isolated during the Tugela Ferry outbreak. Using a variety of whole genome comparative approaches, 11 drug-resistant clones of M.tb circulating from 2008 to 2013 were identified, including a 50-member clone of XDR M.tb that was highly related to the Tugela Ferry XDR outbreak strain. It was calculated that the evolutionary trajectory from first-line drug resistance to XDR in this clone spanned more than four decades and began at the start of the antibiotic era. It was also observed that frequent de novo evolution of MDR and XDR was present, with 56 and 9 independent evolutions, respectively. Thus, ongoing amplification of drug-resistance in KwaZulu-Natal is driven by both clonal spread and de novo acquisition of resistance. In drug-resistant TB, isoniazid resistance was overwhelmingly the initial resistance mutation to be acquired, which would not be detected by current rapid molecular diagnostics that assess only rifampicin resistance

Molecular evolution and dating of drug resistance emergence within the Tugela Ferry XDR Clone.

<p>Midpoint rooted maximum-likelihood phylogeny of 107 <i>M</i>. <i>tuberculosis</i> isolates of the LAM4 spoligotype. The gray shaded box identifies the Tugela Ferry XDR Clone. KZN605, the historical XDR strain collected in Tugela Ferry during the outbreak, is a member of this clone. Two additional historical isolates, KZN1435 and KZN4207, are not members of the Tugela Ferry XDR Clone. Each evolutionary gain of a drug resistance mutation was assigned to its position on the phylogenetic tree by parsimony (colored circles). A–E traces the stepwise order of drug resistance acquisition in the Tugela Ferry XDR Clone and estimates the year when each mutation was gained. Gray bars indicate the 95% highest posterior density (HPD) intervals. (A) <i>katG</i> S315T (isoniazid); <i>gidB</i> 130 bp deletion (streptomycin); 1957 (95% HPD: 1937–1971); (B) <i>inhA</i> promoter -8 (isoniazid and ethionamide); 1964 (95% HPD: 1948–1976); (C) <i>embB</i> M306V (ethambutol); 1967 (95% HPD: 1950–1978); (D) <i>rpoB</i> L452P (rifampicin); <i>pncA</i> 1bp insertion (pyrazinamide); 1984 (95% HPD: 1974–1992); and (E) <i>rpoB</i> D435G (rifampicin); <i>rrs</i> 1400 (kanamycin); <i>gyrA</i> A90V (ofloxacin); 1995 (95% HPD: 1988–1999). The accumulation of individual drug-resistant mutations within a strain is denoted to the right of the phylogenetic tree. The dates of drug discovery are displayed at the bottom of the figure [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001880#pmed.1001880.ref053" target="_blank">53</a>]. Four additional LAM4 strains on a distant branch were not included in this figure because of size constraints. Bootstrap values are provided for lettered nodes, and bootstrap values for all nodes are shown in S5 Fig.</p