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      Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

      , , , , , , ,
      Journal of Fungi
      MDPI AG

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          Abstract

          A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system.

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          Resistance to trimethoprim-sulfamethoxazole.

          P Huovinen (2001)
          Sulfonamides have a glorious history. In 1935, they were the first class of true antimicrobial agents with life-saving potency. Today, 66 years later, increased bacterial resistance to sulfonamides and to trimethoprim (TMP), a synthetic antimicrobial agent that is 30 years younger than sulfonamides, has limited their use to only a few indications. In the treatment and prophylaxis of patients with urinary tract infections, trimethoprim-sulfamethoxazole (TMP-SMZ) or TMP alone is still considered the first-line drug of choice, although increased bacterial resistance to these agents has been linked with treatment failure. TMP-SMZ has a possible role as a second- or third-line treatment for patients who have respiratory tract infections. In the developing world, where this inexpensive drug is widely used as first-line treatment, bacterial resistance has caused problems, especially with regard to the treatment of patients with severe respiratory tract infections. Use of TMP-SMZ as prophylaxis for Pneumocystis carinii infection has rapidly increased the multidrug resistance of bacterial pathogens found in human immunodeficiency virus-infected patients. Today, detailed and reliable knowledge on the resistance of bacterial pathogens to both TMP-SMZ and TMP is an essential requirement for the safe and effective use of these drugs in all clinical settings.
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            A cluster of Pneumocystis infections among renal transplant recipients: molecular evidence of colonized patients as potential infectious sources of Pneumocystis jirovecii.

            Eighteen renal transplant recipients (RTRs) developed Pneumocystis jirovecii infections at the renal transplantation unit of Brest University Hospital (Brest, Brittany, France) from May 2008 through April 2010, whereas no cases of P. jirovecii infection had been diagnosed in this unit since 2002. This outbreak was investigated by identifying P. jirovecii types and analyzing patient encounters. The identification of P. jirovecii internal transcribed spacer (ITS) types was performed on P. jirovecii isolates from the 18 RTRs (12 patients with Pneumocystis pneumonia [PCP], 6 colonized patients), 22 unlinked control patients (18 patients with PCP, 4 colonized patients), and 69 patients (34 patients with PCP, 35 colonized patients) with contemporaneously diagnosed P. jirovecii infections in the Brest geographic area. A transmission map was drawn up. Its analysis was combined with the results of P. jirovecii typing. P. jirovecii ITS type identification was successful in 14 of 18 RTRs, 15 of 22 control patients, and 48 of the 69 patients. Type Eg was the most frequent type in the 3 patient groups. However, its frequency was significantly higher in the first patient group than in the 2 other groups (P < .05 and P < .01, respectively). Fourteen encounters between RTRs who harbored an identical type were observed. Ten patients were considered as possible index patients, of whom 3 were colonized by the fungus, and 7 presented PCP. The results provide to our knowledge the first data on the role of colonized patients as potential sources of P. jirovecii in a context of nosocomial acquisition of the fungus.
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              Sensitivity and specificity of nested and real-time PCR for the detection of Pneumocystis jiroveci in clinical specimens.

              A polymerase chain reaction (PCR)-based test for Pneumocystis jiroveci (formerly Pneumocystis carinii f. sp. hominis) might be an alternative to histologic diagnoses of P. jiroveci pneumonia (PCP). However, previously developed nested PCR methods tend to have low specificities (high false-positive rates). In this study, nested and quantitative real-time PCR methods for the amplification of the P. jiroveci DHPS (dihydropteroate synthase) gene were evaluated in a variety of stored clinical samples from Spain, South Africa, and Brazil. The sensitivities of both assays were high, ranging from 62.5% to 100% depending on the type of specimen. In a subset of 71 microscopically confirmed PCP cases and 70 negative cases, the sensitivities and specificities were 94% and 81% for nested PCR and 94% and 96% for real-time PCR, respectively. Real-time PCR has a statistically significantly better specificity than nested PCR (P = .015) and is likely to generate fewer false positives.
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                Author and article information

                Contributors
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                Journal
                JFOUCU
                Journal of Fungi
                JoF
                MDPI AG
                2309-608X
                October 2021
                October 13 2021
                : 7
                : 10
                : 856
                Article
                10.3390/jof7100856
                8540849
                34682277
                73766df9-9140-4465-818e-c47c46d55b60
                © 2021

                https://creativecommons.org/licenses/by/4.0/

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